US 4,656,166 AGrant
Antibiotic Compounds Derived From Cephalosporins, Process for Their Production and Pharmaceutical Compositions
Issue Date:1987-04-07
•4 Claims
Abstract
The compounds according to the invention correspond to the formula: ##STR1## in which: The COOA group at the 4 position is an acid radical, or an alkaline or alkaline-earth salt, or an amino acid or amine salt, for example triethylamine or ethanolamines, or an easily hydrolyzable or metabolically labile and pharmaceutically acceptable ester radical. X denotes an oxygen atom or a sulfur atom n is zero or 1 R.sub.1 and R.sub.2 each denote independently hydrogen or a lower alkyl group, preferably a methyl group, or R.sub.1 and R.sub.2 taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl nucleus. B is the residue of a primary or secondary amine.
Metadata
Assignee
- Sanofi
Inventors
- Ali Salhi
- Dominique Olliero
Application Information
Application Number:US 6128963
Filing Date:1984-05-22
Priority Date:1983-05-27
Art Unit:122
Classifications
IPC:
C07D50134C07D50136A61K 31545
Field of Search:
54451454027204;;206;207;202226;227;228;222
Patent Drawings
This patent does not have any drawings.
Description
The present invention relates to derivatives of the cephalosporin family, the process for their preparation and their therapeutic use.
The compounds according to the invention correspond to the formula: ##STR2## in which: The COOA group at the 4 position is an acid radical, or an alkaline or alkaline-earth salt, or an amino acid or amine salt, for example triethylamine or ethanolamines, or an easily hydrolyzable or metabolically labile and pharmaceutically acceptable ester radical.
X denotes an oxygen atom or a sulfur atom
n is zero or 1
R.sub.1 and R.sub.2 each denote independently hydrogen or a lower alkyl group, preferably a methyl group, or
R.sub.1 and R.sub.2 taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl nucleus.
B is the residue of a primary or secondary amine selected by the following groups:
Z--NH--R where Z is an alkylene group with a straight or branched chain having from 2 to 7 carbon atoms, possibly interrupted by a sulfur atom and possible substituted by a hydroxyl, thiol, methylthio, amino, acetamido, carbamoyl, phenyl, hydroxyphenyl or imidazolyl group.
Z can also be a cyclopentylidene or cyclohexylidene group. R represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms.
Z'--Alk--NH--R where Z' represents a 1,2-phenylene or 1,3-phenylene or 1,4-phenylene group possibly substituted by a halogen atom or by 1 or 2 methoxy groups or by 1, 2 or 3 methyl groups or Z' represents a 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene group.
Alk represents a straight or branched alkyl group having from 1 to 3 carbon atoms.
R is as defined above. ##STR3## where Z' is as defined above.
Y denotes an alkyl group (CH.sub.2).sub.m in which m=0, 1, 2, 3 or 4, a branched alkyl group having 2 or 3 carbon atoms or also Y with NH--R" constitutes a ring ##STR4## R' and R", identical or different, have the same meaning as that given for R above.
Z"--NH--R where Z" is a 1,3-cyclohexylene or 1,4-cyclohexylene and R is as previously defined. ##STR5## where R.sub.3 represents a hydrogen atom or a methyl group. n=0 or 1 and Alk and R are as previously defined.
A 2-piperidyl, 3-piperidyl or 4-piperidyl group possibly substituted on the nitrogen atom by a --CO--Alk--NH.sub.2 group ##STR6## where Alk is as previously defined.
The salts that the compounds of Formula 1 can give with pharmaceutically acceptable acids form an integral part of the invention.
As a result of the presence in the formula of an oxime group, the compounds (I) exist in two isomeric forms syn and anti. The syn isomers whose therapeutic activity is higher are the preferred compounds.
It is understood that the compounds (I) indicated above can exist:
either in the form indicated in Formula (I),
or in tautomeric form (I'): ##STR7## in which A, X, R.sub.1, R.sub.2, B and n have the previously indicated meanings.
The invention also relates to a process for the preparation of compounds of Formula (I).
According to the reaction diagram below, this process consists of first of all acylating 4-tertiobutyl-1-S-oxide 7-amino-3-bromomethyl-3-cepheme carboxylate (II) with the acid (III) to obtain the compound (IV) described in European patent application No. 60,745. To the compound TV, is then added the acid B--(CH.sub.2).sub.n --COOH or the thioacid B(CH.sub.2).sub.n COSH whose amine function must be previously protected, according to a known method, by a protective group like tertiobutoxycarbonyl or trichlorethoxycarbonyl, for example, B' then represents the group B in which the amine function is protected.
The addition of the sodium or potassium salt of the acid B'--(CH.sub.2).sub.n COOH to the compound (IV) is preferably done in an aprotic polar solvent, for example dimethylformamide, whilst the addition of the sodium or potassium salt of the thioacid B'--(CH.sub.2)HD nCOSH can be done in an apolar solvent like tetrahydrofuran. The compound (V) is obtained.
In the case of the thioacids, to prepare the compounds (V), it is possible to use the thioacid itself instead of an alkali salt. The operation is then in anhydrous acetone in the presence of potassium bicarbonate and sodium iodide.
Finally, to end with the compound (I), the protective groups on the amines and the tertiobutyl esters are removed by a known process, in particular by hydrolysis in an acid medium by using, for example, trifluoracetic acid or a mixture of formic acid and hydrochloric acid. ##STR8## T.sub.r represents trityl, tBu tertiobutyl, X, R.sub.1, R.sub.2, n, B' and B have the previously indicated meanings.
The compounds (I) of the invention in which A is other than H are obtained from compounds (I) in which A is H by reactions known in themselves.
Thus the inorganic salts are obtained by the action on compounds (I), in which A is H, of an inorganic base such as soda or potash or sodium bicarbonate in an equimolecular amount; the salification reaction is carried in a solvent such as water or ethanol and the salt obtained is isolated by evaporation of the solution.
The salts of organic bases are obtained by the action on a solution of the acid I (A=H), in a solvent or a mixture of suitable solvents, of an equimolecular amount of the organic base. The salt is isolated by precipitation with ether.
The esters are obtained by known esterification processes; for example there will advantageously be used the action of a halogen derivative on a salt such as the sodium salt of the acid; preferably the reaction will be carried out in a solvent capable of dissolving the starting acid derivative, for example in dimethylformamide.
The syn and anti form isomers are obtained by a suitable choice of reagents.
the following examples enable the scope of the invention to be further understood without however limiting it.
Thus as is usual in this family of compounds, the products according to the invention do not have a distinct melting point but only points of decomposition which do not permit them to be characterized.
The products will therefore be characterized by their nuclear magnetic resonance spectrum recorded at 60 MHz or at 250 MHz, the internal standard being hexamethyldisiloxane. The spectra are recorded in deuteriated dimethylsulfoxide with the exceptions indicated in the description of the spectrum: 50 mg of product in 0.5 ml of solvent at 60 MHz and 10 mg in 0.5 ml at 250 MHz. The chemical displacements are measured at .+-.0.01 ppm and the coupling constants at .+-.0.5 Hz.
The following abbreviations will be used:
S: singlet
D: doublet
D of D: doublet of doublet
S.e.: widened singlet
M: multiplet
Q: quadruplet
AB: AB system
J: represents the coupling constant.
In addition elementary microanalyses were carried out in each case and are in agreement with the formulae indicated.
The infra-red spectra also serve to characterize the products obtained. They were recorded between 4,000 cm.sup.-1 and 600 cm.sup.-1 from a preparation constituted by a potassium bromide tablet containing the product at a concentration of about 2%; when the spectrum is recorded in solution at 1% in a chlorinated solvent, the nature of the latter is mentioned. The elongation vibration frequency of the carbonyl groups of the molecule is noted (.nu.CO).
EXAMPLE 1
7-[2-(2-Amino 4-thiazolyl)2-(2-carboxy 2-propyl oxyimino)acetamido]3-(4-piperidinyl)carbonyl oxymethyl 3-cepheme 4-carboxylic1.beta.-S-oxide acid trifluoroacetate syn isomer. SR 41 862
(a) 7-[2-(2-tritylamino-4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido]3-(1-tertiobutoxycarbonyl 4-piperidinyl carbonyl oxymethyl)3-cepheme 1-.beta.-S-oxide carboxylate of Tertiobutyl; syn isomer ##STR9## tBu and T have the previously indicated meanings, Boc denotes the tertiobutoxycarbonyl group.
To a solution of 1.38 g of 4-tertiobutyl 1-.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer, in 20 ml of anhydrous dimethylformamide, are added 1 g of 1-tertiobutyloxycarbonyl 4-piperidinyl carboxylic acid and 1.5 g of potassium bicarbonate.
After 17 hours of stirring at ambiant temperature (20.degree.-25.degree. C.) the reaction mixture is poured on to 200 ml of ice water. After vigorous stirring, the crystals were filtered and washed with water. They are then taken up with 70 ml of dichloromethane. The organic phase is then washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated. The lacquer obtained is chromatographed on a column of 50 g of silica. It is eluted with a dichloromethane-ethyl acetate mixture 90-10 (vol/vol). After evaporation of the fractions containing the compound and trituration in hexane, 1.3 g of the expected compound is obtained.
IR Spectrum: .differential. CO 1805 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactame; 1735 cm.sup.-1 : C.dbd.O of the tertiobutyl esters and of the ester at the 3 position; 1695 cm.sup.-1 : C.dbd.O of the tertiobutoxycarbonyl protecting group of the piperidine.
NMR Spectrum at 250 MHz. 1H at 8.75 ppm (S, NHTr)--1H at 8.10 ppm (D, J=9 Hz, CONH)--15H at 7.25 ppm (M, H aromatics)--1H at 6.73 ppm (S, H thiazole)--1H at 5.81 ppm (M, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.55 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.79 ppm (D, J=12 Hz, HCN Boc equatorials)--1H at 3.53 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, HCH Boc arials)--1H at 2.50 ppm (M, HCCO.sub.2)-- 2H at 1.75 ppm (D, J=12 Hz, HCHCO.sub.2 equatorials)--9H at 1.46 ppm (S, CO.sub.2, tBU)--2H at 1.40 ppm (M, HCCHCO.sub.2 axials)--6H at 1.39 ppm (S, (CH.sub.3).sub.2 C)--9H at 1.36 ppm (S, CO.sub.2 tBU)--9H at 1.29 ppm (S, Boc N).
(b) SR 41 862
0.8 g of the compound obtained above was dissolved in 10 ml of trifluoroacetic acid. After 45 minutes at 23.degree. C. the acid was evaporated under vacuum without heating and the oily residue was crystallized by the addition of 50 ml of isopropyl ether. The crystals were filtered and washed with isopropyl ether and then with hexane. They were then dried under vacuum over phosphoric anhydride. 0.66 g of the expected products was obtained.
IR Spectrum: .differential. CO 1795 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactam; 1735 cm.sup.-1 : C.dbd.O of the ester at 3; 1680 cm.sup.-1 wide band: C.dbd.O of the acids of the molecule, of the amide at 7, of the ions CF.sub.3 CO.sub.2.sup.-.
NMR Spectrum at 250 MHz. 2H at 8.60 ppm (S.e., NH.sub.2.sup.+)--1H at 8.50 ppm (D, J+9 Hz, CONH)--3H at 8.40 ppm (S.e., NH.sub.3.sup.+)--1H at 6.68 ppm (S, H thiazole)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.25 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.66 ppm (M, CHCO.sub.2)--2H at 1.90 ppm (M, CH.sub.2 CH)--2H at 1.70 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
EXAMPLE 2
7-[2-(2-amino 4-thiazolyl)2-(2-carboxy 2-propyl oxyimino)acetamido](3-amino propionyl)3-thiomethyl 3-cepheme 4-carboxylic .beta.1-S-oxide acid trifluoracetate syn isomer SR 41884
(a) Tertiobutoxycarbonyl 3-amino thiopropionic acid
1.8 g of tertiobutoxycarbonyl 3-amino propionic acid was solubilized in 50 ml of anhydrous dichloromethane. The triple-neck flask was provided with a calcium chloride trap and cooled in a bath of water and ice. In order, there were added 1.4 ml of triethylamine and 1.3 ml of isobutyl chloroformate. After 20 minutes stirring in the cold, 1.5 ml of triethylamine was added and a light current of hydrogen sulfide was bubbled through for 15 minutes. then the mixture was stirred in the cold for 45 minutes before being evaporated to dryness. 150 ml of sulfate buffer (pH 2) were added and the thioacid was extracted twice with 70 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and evaporated.
The oily product obtained was used as such.
(b) 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido](3-tertiobutoxycarboxylamino propionyl)3-thiomethyl 3-cepheme 1.beta.-S-oxide carboxylate of 4-Tertiobutyl; syn isomer
To a solution of 0.46 g of 4-Tertiobutyl 1.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutyoxycarbonyl 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer, in 10 ml of tetrahydrofurane, were added 0.4 g of the thioacid described above as well as 0.6 g of potassium bicarbonate. After 4 hours stirring at ambiant temperature the solvent was evaporated and the residue taken up again with 100 ml of water and 50 ml of dichloromethane. After decantation the aqueous phase was extracted with 50 ml of dichloromethane. The organic phases were combined, dried over magnesium sulfate and evaporated.
The lacquer so obtained was chromatographed on a column of silica (40 g), it was eluted with a mixture of dichloromethane-ethyl acetate 90-10 (vol/vol).
IR Spectrum: .differential. CO 1805 cm: C.dbd.O at 8 of the .beta. lactame; 1720 cm: C.dbd.O of the tertiobutylic esters; 1690 cm: C.dbd.O of the amide at 7, of the thioester at 3 and of the tertiobutoxy carbonyl protecting the amine.
NMR Spectrum at 250 MHz (CDCL.sub.3). 1H at 7.75 ppm (D, J=9 Hz, CONH)--15H at 7.27 ppm (M, H ar Trit)--1H at 6.95 ppm (S.e., NH--Trit)--1H at 6.63 ppm (S, H thiazole)--1H at 6.21 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.85 ppm (S.e., NH--Boc)--1H at 4.50 ppm (D, J=4 Hz, H.sub.6)--1H at 4.29 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.58 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.36 ppm (M, CH.sub.2 NH Boc)--1H at 3.22 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (T, J=6 Hz, CH.sub.2 --CS)--15H at 1.52 ppm (S, Boc NH and (CH.sub.3).sub.2 C)--18H at 1.39 ppm (2S, CO.sub.2 tBu).
(c) SR 41 884
The whole of the compound obtained above was solubilized in 10 ml of trifluoroacetic acid. After 45 minutes at 23.degree. C. the acid was evaporated under vacuum without heating, and the oily residue was crystallized by the addition of 50 ml of isopropyl ether. The crystals were filtered and washed with isopropyl ether and then with hexane. They were then dried under vacuum over phosphoric anhydride.
0.37 g of the expected product was obtained.
IR Spectrum: .differential. CO 1785 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactam 1680 cm.sup.-1 wide band: C.dbd.O of the acids of the molecule, of the amide at 7, of the thioester, of the CF.sub.3 CO.sub.2.sup.- ions.
NMR Spectrum at 250 MHz. 1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., NH.sub.3.sup.+)--3H at 7.30 ppm (S.e., NH.sub.3.sup.+)--1H at 6.78 ppm (S, H, thiazole)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.18 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.79 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.66 ppm (S, CH.sub.2 SO)--2H at 3.0 ppm (M, CH.sub.2 NH)--2H at 2.92 ppm (M, CH.sub.2 COS)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
EXAMPLE 3
Trifluoroacetate of 7 -[2-(2-amino 4-thiazoyl)2-(2-carboxy 2-propyl oxyimino)acetamido](3-amino propionyl)3-thiomethyl 3-cepheme 4-carboxylic 1.beta.-S-oxide acid; syn isomer, SR 41884
(a) 7-[2-(2-tritylamino 4-thiazolyl)2-tertiobutoxy 2-(carbonyl 2-propyl oxyimino)acetamido](3-tertiobutoxy carbonylamino)3-thiomethyl 3-cepheme 1.beta.-S-oxide carboxylate of 4-Tertiobutyl; syn isomer
To 0.46 g of 4-Tertiobutyl 1.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxy carboxylamino 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer in 10 ml of anhydrous acetone, were added 0.4 g of 3-tertiobutoxycarvonylamino thiopropionic acid, 0.6 g of potassium bicarbonate and 0.25 g of sodium iodide.
After 2 hours stirring at room temperature, the solvent was evaporated to dryness. The residue was taken up again in 100 ml of water and extracted with 50 ml of dichloromethane. The organic phase is separated and the aqueous phase reextracted with 50 ml of dichloromethane. The organic extracts were combined, dried over magnesium sulfate and evaporated to dryness.
The product obtained was chromatographed on a silica column by eluting with a dichloromethane-ethyl acetate mixture 90-10 (vol/vol).
An identical product (IR spectrum and NMR spectrum) to the product of Example 2(b) was obtained.
(b) SR 41 884
The deprotection was carried out as indicated in Example 2(c).
By operating as in Example 1, the compounds according to the invention were prepared in the form of trifluoroacetate, described in Table I below. ##STR10##
These compounds are identified by a reference number. For each among them the values of R.sub.1, R.sub.2, B and n and the NMR spectrum are given.
The acid B'--(CH.sub.2).sub.n --COOH which reacts on (IV) to give (V) is an aminoacid of the L series or of the D series or racemic; the corresponding indication appears in Table I, at column B.
The chromatographic eluant is also given which serves to isolate (V): the last intermediate product before deblocking the acid and amine functions of the molecule. This intermediate V is characterized by its infra-red spectrum, the wavelengths indicated in cm.sup.-1 correspond in order to the elongation vibration frequencies of the carbonyl at the 8 position of the beta lactam, the tertiobutylic esters and the ester at the 3 position, the amide at the 7 position and the carbamate protecting the amine. When 2 wavelengths only are indicated, the second corresponds to a wide band which covers the elongation vibration frequencies both of the esters, of the amide and of the protective carbamate of the amine.
The list of NMR spectra of the compounds mentioned in Table I is given following this table.
NMR SPECTRA: The spectra are recorded at 60 MHz, indicated by (a) or at 250 MHz, indicated by (b); when there exist two diastereo-isomers in a molecule, the split signals are indicated by *.
NMR no. 1-(b): 1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.18 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.64 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.61 ppm (M, CH.sub.2 CO.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 2-(b): 4H at 8.45 ppm (M, N.sup.+ H.sub.3, CONH)--3H at 7.35 ppm (S.e., N.sup.+ H.sub.3)--5H at 7.25 ppm (M, H aromatics--1H at 6.82 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.31 ppm (S.e., CHNH.sub.2)--1H at 3.50 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.30 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.10 ppm (M, CH.sub.2 C.sub.6 H.sub.5 )--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 3-(b): 5H at 8.45 ppm (S.e., N.sup.+ H.sub.2, OH, CONH)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--2H at 6.95 ppm (D, J=8 Hz, H meta OH)--1H at 6.78 ppm (S, H thiazol)--2H at 6.68 ppm (D, J=8 Hz, H ortho OH)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.74 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.19 ppm (M, CHNH.sub.2)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.34 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.93 ppm (M, CH.sub.2 --CH--NH.sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 4-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e. N.sup.+ H.sub.3)--3H at 7.60 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3).sub. 2 C)--3H at 1.34 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 5-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.60 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hzn H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 3.92 ppm (M, CHNH.sub.2 and CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 2.11 ppm (M, CH(CH.sub.3).sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C)--6H at 0.9 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 6-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.35 ppm (S.e., N.sup.+ H.sub.3)--4H at 7.40 ppm (S.e., CONH.sub.2, N.sup.+ H.sub.3)--1H at 6.92 ppm (S.e., CONH.sub.2)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.20 ppm (M, CH.sub.2 --CONH.sub.2)--2H at 1.95 ppm (M, CH.sub.2 --CH)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 7-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.16 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.81 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OH)--1H at 3.69 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OH)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 8-(a): 8H between 5.5 and 8.5 ppm (widened signal, NH.sub.2, CO.sub.2 H, TRA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.82 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.67 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J=17 Hz; CH.sub.2 SO)--1H at 3.62 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO.sub.2)--2H at 1.80 (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.43 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 9-(a): 8H between 5.5 and 8.7 ppm (wide signal, CO.sub.2 H, NH.sub.2, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.30 ppm (M, CH.sub.2 CO)--12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2).
NMR no. 10-(a): 8H between 5.5 and 8.0 ppm (wide signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1 H at 3.85 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.62 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.30 ppm (M, CH.sub. 2 CO.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--10H at 1.35 ppm (S.e., CH.sub.2 (CH.sub.2).sub.5 CH.sub.2).
NMR no. 11-(a): 2H at 8.40 ppm (M, CONH, CH.sub.3 CONH)--8H at 7.50 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--3H at 4.30 ppm (M, CH.sub.2 NHCOCH.sub.3, CHNH.sub.2)--1H at 4.00 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 S)--3H at 1.80 ppm (S, CH.sub.3 CONH)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 12-(a): 8H between 6.5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.5 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.67 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--12H at 1.45 ppm (S, (CH.sub.3).sub.2 C--CO.sub.2 H, (CH.sub.3).sub.2 CNH.sub.2).
NMR no. 13-(a): 8H between 6.5 and 9.5 ppm (wide signal, CO.sub.2 H, NH.sub.2, TFA)--1H 8.5 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--3H at 3.80 ppm (M, CHNH.sub.2 and CH.sub.2 SO)--3H at 1.50 ppm (M, CH.sub.2 --CH)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--6H at 0.85 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 14-(a): 8H between 7 and 9 ppm (wide signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H 6.08 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6) 1H at 4.49 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--3H at 3.90 ppm (M, CH.sub.2 SO and CHCH.sub.2) 1H at 1.80 ppm (M, CHCH.sub.3)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--2H at 1.30 ppm (M, CH.sub.2 CH.sub.3)--6H at 0.88 ppm (M, CH.sub.3 CH.sub.2 and CH.sub.3 CH).
NMR no. 15-(b):
1H at 8.5 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.10 ppm (M, CH--NH.sub.2)--1H at 3.97 ppm (M, CH--OH)--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.14 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 16-(b): 1H at 8.5 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 7.66 ppm (S, CONH.sub.2)--3H at 7.50 ppm (S.e., N.sup.30 H.sub.3)--1H at 7.22 ppm (S, CONH.sub.2)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.29 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.26 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.52 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.71 ppm (M, CH.sub.2 CONH.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 17-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.45 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.45 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.13 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 2.50 ppm (M, CH.sub.2 S)-- 5H at 2.0 ppm (M, CH.sub.3 S et CH.sub.2 --CH.sub.2 --S)--6H at 1.44 ppm S, (CH.sub.3).sub.2 C).
NMR no. 18-(b): 4H at 8.50 ppm (M, CONH, N.sup.+ H.sub.3)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.97 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2, --1H at 1.75 ppm (MCH.sub.2 CH)--11H at 1.40 ppm (S.e., (CH.sub.3).sub.2 C, (CH.sub.2).sub.3 CH.sub.2 NH.sub.2).
NMR no. 19-(b): 1H at 9 ppm (S, H.sub.2 imidazol)--3H at 8.6 ppm (S.e., N.sup.+ H at 8.5 ppm (D, J=9 Hz, CONH)--1H at 7.40 ppm (S, H.sub.4 imidazol)--3H 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.22 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.40 ppm (M, CHNH.sub.2)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.52 ppm (D, J= 17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 20-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.77 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.76 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.63 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3 ).sub.2 C)--3H at 1.36 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 21-(a): 8H between 6.5 and 9 ppm (widened signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.35 ppm (D, J=9 Hz, CONH)--1H at 6.80 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2) 2H at 2.35 ppm (M, CH.sub.2 CO)--10H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C+CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 22-(a): 8H between 6 and 9 ppm (wide signal, TFA, NH.sub.2, CO.sub.2 H)--1H at 8.42 ppm (D, J=9 Hz, CONH)--1H at 6.85 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H 4.68 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--8H at 1.75 ppm (M, H, cyclopentane)--6H at 1.45 ppm (S, (CH.sub.3).sub. 2 C).
NMR no. 23-(a): 8H between 7 and 10 ppm (wide signal, TFA, NH.sub.2, CO.sub.2 H)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.92 ppm (S, H thiazol)--1H 6.10 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.35 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.70 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--16H between 1 and 2.3 ppm (M, (CH.sub.3).sub.2 C and cyclohexane).
NMR no. 24-(a): 9H between 8 and 10 ppm (wide signal, NH.sub.2, OH, CO.sub.2 H, TFA)--1H at 8.55 ppm (D, J=9 Hz, CONH)--2H at 7.10 ppm (D, J=8 Hz, H meta OH)--1H at 6.90 ppm (S, H thiazol)--2H at 6.80 ppm (D, J=8 Hz, H ortho, OH)--1H at 6.10 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.80 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.30 ppm (M, CHNH.sub.2)--2H at 3.70 ppm (M, CH.sub.2 SO)--2H at 3.0 ppm (M, CH.sub.2 --C.sub.6 H.sub.4 OH--6H at 1.46 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 25-(a): 10H between 6.5 and 9.5 ppm (wide signal, NH.sub.2, CO.sub.9 H, TFA)--1H at 8.40 ppm (D, J=9 Hz CONH)--1H at 6.85 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.85 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.20 ppm (M, CHNH.sub.2)--2H 3.80 ppm (M, CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.20 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 26-(b): 3H at 8.60 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.44 ppm (D, J=9 Hz, CONH)--1H at 6.78 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--5H between 2.5 and 3.5 ppm (M, CH.sub.2 N et CHCO.sub.2)--4H between 1.5 and 2.0 ppm (M, CH.sub.2).sub.2 CH.sub.2 N)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 27-(b): 3H at 8.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.26 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHCO.sub.2)--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--4H at 1.60 ppm (M, (CH.sub.2).sub.2 CH.sub.2 NH.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 28-(b): 1H at 8.37 ppm (D, J=9 Hz, CONH)--3H at 7.90 (S.e., N.sup.+ H.sub.3)--3H at 7.20 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.50 ppm (M, CHNH.sub.2)--2H at 2.56 ppm (M, CH.sub.2 CHNH.sub. 2) 6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.16 ppm (D, J=6 Hz, CH.sub.3 --CH).
NMR no. 29-(b): 1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.95 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.20 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (M, H.sub.6)--1H at 4.62 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (M, CHCO.sub.2)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)-- 6H at 1.44 ppm (M, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 30-(b): 4H at 8.45 ppm (M, N.sup.+ H.sub.3, CONH)--8H at 7.35 ppm (M, N.sup.+ H.sub.3, H aromatic)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.05 ppm (2D, J=13 Hz, CH.sub.2 OCO)* 1H at 4.94 ppm (2D, J=4 Hz, H.sub.6)*--1H at 4.60 ppm (M, CHNH.sub.2)--1H at 3.66 ppm (2D, J=17 Hz, CH.sub.2 SO)*--1H at 3.40 ppm (2D, J=17 Hz, CH.sub.2 SO)*--2H at 3.0 ppm (M, CH.sub.2 CO.sub.2) 6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 31-(b): 1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.74 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.81 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.16 ppm (M, CHNH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO)-- 1H 1.77 ppm (M, CH.sub.2 CHNH.sub.2)--1H at 1.61 ppm (M, CH.sub.2 CHNH.sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C) 1H at 1.0 ppm (D, J=7 Hz, CH.sub.3 --CH).
NMR no. 32-(a): 7H between 7 and 9 ppm (NH, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.90 ppm (M, CH.sub.2 NH)--3H at 2.45 ppm (D, J= 6 Hz, CH.sub.3 NH)--2H at 2.4 ppm (M, CH.sub.2 CO)--2H at 1.70 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.42 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 33-(a): 7H between 7 and 9.5 ppm (NH.sub.2, NH, CO.sub.2 H, TFA)--1H at 8.46 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO) 1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NHCH.sub.3)--5H 2.45 ppm (M, CH.sub.3 NH and CH.sub.2 CO)--10H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 34-(a): 8H between 6 and 9 ppm (widened signal, NH.sub.2, TFA, OH, CO.sub.2 H)--1H at 8.47 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.15 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz--H.sub.7)--1H at 5.35 ppm (AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.85 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--4H at 3.95 ppm (M, CH.sub.2 SO and CHOHCHNH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (D, J=7 HZ, CH.sub.3 CHOH).
NMR no. 35-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.35 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--1H at 6.84 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.1 ppm (M, CH.sub.2 NH.sub.2, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 36-(a): 3H at 9.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.55 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.92 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.0 ppm (S.e., CH.sub.2 NH.sub.2)-- 6H at 1.45 ppm (S, (CH.sub.3).sub.2 C--ON)--6H at 1.17 ppm (S, (CH.sub.3).sub.2 CO.sub.2 CH.sub.2).
NMR no. 37-(b): 8H between 5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J=9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.9 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.54 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.6 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.25 ppm (T, J=12 Hz, CHCO.sub.2)--4 H at 1.84 ppm (M, CH.sub.2 CHCO)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.25 ppm (M, CHCH.sub.2 NH.sub.2 and CH.sub.2 CHCH.sub.2 NH.sub.2)--2H at 0.95 ppm (M, CH.sub.2 CHCH.sub.2 NH.sub.2).
NMR no. 38-(b): 1H at 8.37 ppm (D, J=9 Hz, CONH)--3H at7.90 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.59 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (S.e., CHNH.sub.2)--1H at 2.40 ppm (M, CHCO.sub.2)--1H at 2.10 ppm (M, CH.sub.2 CHNH.sub.2)--3H at 1.80 ppm (M, CH.sub.2 CHNH.sub.2)--6H 1.44 ppm (2S, (CH.sub.3).sub.2 C)--4H between 1 and 1.5 ppm (M, CH.sub.2 --CH.sub.2 --CH--CO.sub.2).
NMR no. 39-(b): 1H at 8.5 ppm (D, J=9 He, CONH)--6H between 7 and 8 ppm (wide signal, NH.sub.2, TFA)--1H at 6.81 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J=9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm D, J=17 Hz, CH.sub.2 SO)--2H at 2.77 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.52 ppm (M, CHCO.sub.2)--1H at 1.84 ppm (M, CH.sub.2 CH)--1H at 1.56 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.06 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 40-(a): 1H at 8.45 ppm (D, J=9 Hz, CONH)--8H at 7.30 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.80 ppm S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.20 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO) 1H at 4.90 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.90 ppm (D, J=4 Hz, H.sub.6)--3H at 3.80 ppm (M, CH.sub.2 SO, CHNH.sub.2)--1H at 2.00 ppm (M, CH(CH.sub.3).sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--6H at 0.95 ppm (2D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 41-(a): 2H at 8.50 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, 13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 NH)--5H at 2.50 ppm (M, CH.sub.3 NH, CH.sub.2 CO.sub.2)-- 6H at 1.42 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 42-(a): 7H at 9.4 ppm (S.e., N.sup.+ H.sub.3, N.sup.+ H.sub.2, CO.sub.2 H)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 6.85 ppm (S, H thiazol)--1H at 6.00 ppm (M, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--4H at 2.85 ppm (M, CH.sub.2 NHCH.sub.2)--2H at 2.40 ppm (M, ##STR156## 2H at 1.80 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH)--6H at1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2 NH).
NMR no. 43-(a): 2H at 8.50 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.00 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 pm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 5.10 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.50 ppm, B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.30 ppm (M, CHNH)--5H at 2.45 ppm (M, CH.sub.3 NH and ##STR157## 2H at 1.80 ppm (M, ##STR158## 6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 44-(a): 1H at 8.40 ppm (D, J=9 Hz, CONH)--7H at 7.80 ppm (S.e., N.sup.+ H.sub.3, N.sup.+ H.sub.2, CO.sub.2 H)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (M, H.sub.7)--1H at 5.00 ppm (M, H.sub.6)--1H at 5.00 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz), CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH)--5H at 2.40 ppm (M, CH.sub.3 NH, CH.sub.2 CO.sub.2)--12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2 NH).
NMR no. 45-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.91 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 3.84 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.64 ppm (M, CHCO.sub.2)--2H at 1.95 ppm (M, CH.sub.2 CH.sub.2 NH)--2H at 1.66 ppm (M, CH.sub.2 CH.sub.2 NH).
NMR no. 46-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.64 ppm (M, CHCO.sub.2)--4H at 2.40 ppm (M, ##STR159## 6H between 1.5 and 2 ppm ##STR160## CH.sub.2 --CH.sub.2 NH).
NMR no. 47-(b): 1H at 8.79 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.97 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.56 ppm (S, CH.sub.2 ON)--1H at 4.08 ppm (M, CH.sub.2 NH.sub.2)--1H at 4.00 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO).
NMR no. 48-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.95 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz)--CH.sub.2 OCO)--1H at 4.10 ppm (S.e., CH.sub.2 NH.sub.2)--1H at 4.05 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--4H 2.40 ppm (M, ##STR161## 2H at 1.85 ppm (M, ##STR162##
NMR no. 49-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.53 ppm (S, CH.sub.2 ON)--1H 3.84 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.76 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO.sub.2)--2H at 1.72 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2).
NMR no. 50-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.25 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.77 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.78 ppm (M, CH.sub.2 NH.sub.2)--6H at 2.40 ppm (M, ##STR163## CH.sub.2 CO.sub.2)--4H at 1.85 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2, ##STR164##
NMR no. 51-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.60 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.87 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.57 ppm (S, CH.sub.2 ON)--1H at 3.81 ppm (A of AB, J=13 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=13 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.31 ppm (M, CH.sub.2 CO.sub.2)--4H at 1.50 ppm (M, CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 N).
NMR no. 52-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.74 ppm (M, CH.sub.2 NH.sub.2)--6H at 2.40 ppm (M, ##STR165## 2H at 1.85 ppm (M, ##STR166## 4H at 1.50 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 CO.sub.2).
NMR no. 53-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR167## 2H at 1.80 ppm (M, ##STR168## 3H at 1.36 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 54-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.87 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.19 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.64 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.92 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (M, CHCO.sub.2)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--4H at 2.40 ppm (M, ##STR169## 2H at 1.80 ppm (M, ##STR170## 3H at 1.08 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 55-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 5.20 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (S.e., H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (B of AB, J=17 Hz, CH.sub.2 SO) 2H at 2.93 ppm (M, CH.sub.2 NH.sub.2)--4H at 2.40 ppm (M, ##STR171## 2H at 1.90 ppm (M, ##STR172## 6H at 1.14 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 56-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.35 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.74 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.50 (M, CHCO.sub.2)--4H at 2.40 ppm (M, ##STR173## 3H at 1.90 ppm (M, ##STR174## and CH.sub.2 CH.sub.2 NH.sub.2)--1H at 1.55 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.08 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 57-(b): 1H at 8.80 ppm (D, H=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.28 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.61 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR175## 2H at 2.10 ppm (M, CH.sub.2 cyclopentane)--2H at 1.90 (M, ##STR176## 6H at 1.80 ppm (M, CH.sub.2 cyclopentane).
NMR no. 58-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 2.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.89 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--3H at 4.55 ppm (M, CH.sub.2 ON and CH.sub.2 OCO)--1H at 3.82 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.21 ppm (M, CHCO.sub.2)--4H at 1.80 ppm, (M, CH.sub.2 cyclohexane)--1H at 1.45 ppm (M, CHCH.sub.2 NH.sub.2)--2H at 1.25 ppm (M, CH.sub.2 cyclohexane)--2H at 0.90 ppm (M, CH.sub.2 cyclohexane).
NMR no. 59-(b): 1H at 8.67 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3,87 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--5H between 2.0 and 2.5 ppm, 6H between 1.6 and 2.0 ppm, 3H between 1.1 and 1 6 ppm, 2H at 0.90 ppm (M, ##STR177##
NMR no. 60-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH.sub.2 OCO+CHON)--1H at 3.86 ppm (2D, J=17 Hz, CH.sub.2 SO)*--1H at 3.56 ppm (2D, J=17 Hz, CH.sub.2 SO)*--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (T, J=7 Hz, CH.sub.2 CO.sub.2)--2H at 1.75 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.39 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 61-(b): 1H at 8.70 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.12 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (2D, H.sub.6)*--2H at 4.60 pm (M, HCON, and CH.sub.2 OCO)--1H at 3,86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.31 ppm (M, CH.sub.2 CO.sub.2)--4H at 1.50 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 62-(b): 2H at 8.60 ppm (M, CONH, N.sup.+ H.sub.3)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.14 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH--ON, and CH.sub.2 OCO)--1H at 3.88 ppm (2D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm and 2H at 2.95 ppm (M, ##STR178## 1H at 2.66 ppm (M, CHCO.sub.2)--2H at 1.95 ppm and 2H at 1.70 ppm (M, ##STR179## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 63-(b): 1H at 8.70 ppm (2D, J=9 Hz, CONH)*--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.95 ppm (D, J=Hz, H ortho CO.sub.2)--2H at 7.55 ppm (D, J=8 Hz, H meta CO.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3) 1H at 6.82 ppm (2S, H thiazol)*--1H at 5 95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (2D, H.sub.6)*--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.60 ppm (Q, J=7 Hz, CHON)--2H at 4.10 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 64-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--5H between 4 and 6 ppm (S.e., N.sup.+H.sub.3 CO.sub.2 H)--1H 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH.sub.2 OCO and CHON)--1H at 3.86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.61 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.21 ppm (M, CHCO.sub.2)--4H at 1.80 ppm (M, ##STR180## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH)--2H at 1.25 ppm and 2H at 0.90 ppm (M, ##STR181##
NMR no. 65-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.05 ppm (S, HAr 2')--1H at 7.94 ppm (D, J=7 Hz, HAr 6')--1H at 7.71 ppm (D, J=7 Hz, HAr 4')--1H at 7.55 ppm (T, J=7 Hz, H5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, CH.sub.3)--3H at 1.47 ppm (S, CH.sub.3).
NMR no. 66-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (2D superposed, J=13 Hz, CH.sub.2 OCO)--1H at 5.10 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (2D superposed, J=13 Hz, CH.sub.2 OCO)--4H at 3.90 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup..sym. H.sub.3)--3H at 2.80 ppm (M, CHCO.sub.2, CHCH.sub.2 N.sup..sym. H.sub.3, and H Eq in .alpha. du CO.sub.2)--1H at 2.00 ppm (M, H Ax in .alpha. of CO.sub.2)--6H at 1.50 ppm (2S (CH.sub.3).sub.2 C)--6H between 1.20 and 1.80 ppm (M, 3CH.sub.2 reminder of cyclohexane.
NMR no. 67-(b): 3H at 8.50 ppm (M, N.sup..sym. H.sub.2 and CONH)--2H at 7.50 ppm (Se., NH.sub.2 thiazol)--1H at 6.79 ppm (S, H thiazol)--1H at 5.99 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz H.sub.6)--1H at 4.66 ppm (D, J=13 Hz, OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.36 ppm (M, CHN.sup..sym. H.sub.2)--1H at 3.25 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--1H at 2.95 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--2H at 2.60 ppm (2D superposed CH.sub.2 CO.sub.2)--3H at 1.70 ppm (M, H piperidine)--6H at 1.48 ppm (2S(CH.sub.3).sub.2 C)--3H at 1.45 ppm (M, H piperidine).
NMR no. 68-(b): 1H at 8.60 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.45 ppm (Se., NH.sup..sym..sub.2 piperidine)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 7.50 ppm (Se., NH.sub.2 thiazol)--1H at 6.70 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5 10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6) 1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.57 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub. 2 .alpha.N.sup..sym. H.sub.2)--2H at 2.70 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--2H at 2.30 ppm (D, J=7 Hz, CH.sub.2 CO.sub.2)--1H at 2.05 ppm (M, CHCH.sub.2 CO.sub.2)--3H at 1.55 ppm (M, CH.sub.2 piperidine)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C)--1H at 1.20 ppm (M, CH.sub.2 piperidine).
NMR no. 69-(b): 1H at 10.9 ppm (Se., ArNHCO)--1H at 8.45 ppm (D, J=9 Hz, CONH)--4H at 8.15 ppm (2S, CH.sub.2 N.sup..sym. H.sub.3 and HAr 2')--1H at 7.81 ppm (D, J=7 Hz, HAr 6')--1H at 7.67 ppm (D, J=7 Hz, HAr 4')--1H at 7.50 ppm (T, J=7 Hz, HAr 5')--2H at 7.20 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (M, ##STR182## and CH.sub.2 SO)--6H 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 70-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.50 ppm (Se., CH.sub.2 --N.sup..sym. H.sub.3)--1H at 8.05 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=7 Hz, HAr 6')--1H at 7.34 ppm (D, J=7 Hz HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub. 3 and CH.sub.2 SO)--1H at 3.80 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.37 ppm (S, CH.sub.3 Ar)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 71-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--9H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.78 ppm (M, HAr 2', 6')--1H at 7.50 ppm (D, J=7 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H of 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H of 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 S0)--3H at 2.36 ppm (S, CH.sub.3 Ar)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 72-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 NHCH.sub.3)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.43 ppm (S, CH.sub.3 N)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 73-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.43 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.18 ppm (M, CH.sub.2 Ar)--1H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub. 2 SO)--2H at 2.90 ppm (M, CH.sub.3 CH.sub.2 NH)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.16 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2).
NMR no. 74-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 NPr)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.20 ppm (M, NH--CH(CH.sub.3).sub.2)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C)--6H at 1.26 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 75-(b): 1H at 8,62 ppm (D, J=9 Hz, CONH)--3H at 8,10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7,68 ppm (D, J=7 Hz, HAr 6')--1H at 7,55 ppm (D, J=7 Hz, HAr 4')--1H at 7,34 ppm (T, J=7 Hz, HAr 5')--1H at 6,92 ppm (S, H thiazol)--1H at 6,00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5,37 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5,00 ppm (D, J=4 Hz, H.sub.6)--1H at 4,84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4,10 ppm (M, CH.sub.2 N.sup. .sym. H.sub.3 et CH.sub.2 SO)--1H at 3,75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2,40 ppm (S, CH.sub.3 Ar)--6H at 1,47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 76-(b): 1H at 8.62 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.31 ppm (D, J=7 Hz, HAr 4')--1H at 7.14 ppm (D, J=7 Hz, HAr 5')--1H at 6.90 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.27 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.92 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.64 ppm (D, J= 17 Hz, CH.sub.2 SO)--6H at 2.18 ppm (S, CH.sub.3 --Ar)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 77 (b): 1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, HAr)--1H at 6.90 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.92 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.65 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.31 ppm (S, CH.sub.3 Ar)--3H at 2.25 ppm (S, CH.sub. 3 Ar)--3H at 2.14 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 78-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.45 ppm (D, J=7 Hz, HAr 4')--2H at 6.92 ppm (M, H thiazol and HAr 5')--1H at 6 00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 3.95 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--3H at 3.78 ppm (S, OCH.sub.3)--3H at 3.73 ppm (S, OCH.sub.3 )--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 79-(b): 1H at 8.62 ppm (D, J=9 Hz, CONH)--5H at 8.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and HAr 2', 6')--1H at 7.20 ppm (D, J=7 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--3H at 3.88 ppm (S, OCH.sub.3)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.47 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 80-(B): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.50 ppm (M, HAr)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--3H at 3.86 ppm (S, CH.sub.3 O--Ar)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, (CH.sub. 3).sub.2 C)--3H at 1.47 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 81-(b): 1H at 8.82 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.13 ppm (Se., HAr 2')--1H at 7.95 ppm (D, J=7 Hz, HAr 6')--1H at 7.69 ppm (D, J=7 Hz, HAr 4')--1H at 7.55 ppm (T, J=7 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.48 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6) 1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR183## 2H at 1.90 ppm (M, ##STR184##
NMR no. 82-(b): 1H at 8.82 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.45 ppm (D, J=7 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR185## 3H at 2.34 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR186##
NMR no. 83-(b): 1H at 8.97 ppm (D, J=9 Hz, CONH)--2H at 8.79 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2)--2H at 8.00 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.58 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--4H at 2.40 ppm (M, ##STR187## 2H at 1.90 ppm (M, ##STR188##
NMR no. 84(b): 1H at 10.7 ppm (S, CONHAr)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.20 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--3H at 7.65 ppm (Se., CH.sub.2 N.sup.+ H.sup.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.05 ppm (Q, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.70 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 85-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--4H at 8.20 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and H thiazol in 3)--1H 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.38 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.98 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.82 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.49 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 86 (b): 1H at 10.75 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.07 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, HAr 2' 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3' 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--3H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 87-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., NH.sub.2.sup..sym. piperidine)--1H at 8.40 ppm (Se., NH.sub.2.sup..sym. piperidine)--2H at 7.40 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5 95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.68 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3 60 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.40 ppm (M, CHN.sup..sym. H.sub.2)--1H at 3.25 ppm (M, CH.sub.2 N.sup..sym. H.sub.2)--1H at 2.89 ppm (M, CH.sub.2 N.sup..sym. H.sub.2)--2H at 2.60 ppm (2D superposed, J=7 Hz, CH.sub.2 COO)--4H at 2.40 ppm (M, ##STR189## 5H at 1.85 ppm (M, 3H of the piperidine and ##STR190## 3H at 1.45 ppm (M, 3H piperidine).
NMR no. 88-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.45 ppm (Se., N.sup..sym. H.sub.2 piperidine)--2H at 7.25 ppm (Se., NH.sub.2 thiazol)--1H at 6.79 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.69 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.24 ppm (M, CH.sub.2 in .alpha. of N.sup..sym. H.sub.2 piperidine)--2H at 2.70 ppm (M, CH.sub.2 in .alpha. of N.sup..sym. H.sub.2 piperidine)--6H at 2.40 ppm (M, ##STR191## and CH.sub.2 COO)--6H between 1.5 and 2.2 ppm (M, ##STR192## CHCH.sub.2 CO.sub.2, 3H piperidine)--1H at 1.20 ppm (M, H piperidine).
NMR no. 89-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--2H at 8.30 ppm (2 Se., NH.sub.2.sup..sym. piperidine)--2H at 7.40 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.14 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.18 ppm (M, H.alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.81 ppm (M, H.alpha.N.sup..sym. H.sub.2 piperidine)--4H at 2.40 ppm (M, ##STR193## 2H at 2.28 ppm (D, J=7 Hz, CH.sub.2 CO--O)--5H at 1.90 ppm (M, ##STR194## CHCH.sub.2 COO, 2H.beta.N.sup..sym. H.sub.2 piperidine) 2H at 1.30 ppm (M, 2H.beta.N.sup..sym. H.sub.2 piperidine).
NMR no. 90-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., NH.sub.2.sup..sym. piperidine)--1H at 8.20 ppm (Se., NH.sub.2.sup..sym. piperidine)--2H at 7.30 ppm (Se., NH.sub.2 thiazol)--1H at 6.77 ppm (S, H thiazol)--1H 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.21 ppm (M, CH.sub.2 and .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.81 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.27 ppm (D, J=7 Hz, CH.sub.2 COO)--1H at 1.95 ppm (M, CHCH.sub.2 COO)--2H at 1.75 ppm (M, CH.sub.2 .beta.N.sup..sym. H.sub.2 piperidine)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--2H at 1.40 ppm (M, CH.sub.2 .beta.N.sup.+ H.sub.2 piperidine).
NMR no. 91-(b): 2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.96 ppm (D, J=8 Hz, Har 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.56 ppm (T, J=8 Hz, Har 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (M, CH.sub.3 N.sup..sym. H.sub.2 CH.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 92-(b): 2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.96 ppm (D, J=8 Hz, HAr 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.56 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.02 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.17 ppm (Se., Ar, CH.sub.2 N.sup..sym. H.sub.2 Et)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.3 CH.sub.2 N.sup..sym. H.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.15 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2 N.sup..sym. H.sub.2).
NMR no. 93(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 --i Pr)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.95 ppm (D, J=8 Hz, HAr 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.58 ppm (T, J=8 Hz, HAr 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J= 13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.2 i Pr)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.79 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.31 ppm (M, (CH.sub.3).sub.2 --CH)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--6H at 1.22 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CHN.sup..sym. H.sub.2).
NMR no. 94-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.66 ppm (D, J=8 Hz, HAr 6')--1H at 7.55 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.07 ppm (M, ArCH.sub.2 N.sup. .sym. H.sub.3 and CH.sub.2 SO)--1H at 3.67 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.40 ppm (S, CH.sub.3 Ar)--4H at 2.50 ppm (M, ##STR195## 2H at 1.90 ppm (M, ##STR196##
NMR no. 95-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.40 ppm (D, J=8 Hz, HAr 4')--1H at 7.20 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.95 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (ArCH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.63 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR197## 6H at 2.20 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR198##
NMR no. 96-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, HAr)--1H at 6.9 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.94 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.62 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.50 ppm (M, ##STR199## 3H at 2.32 ppm (S, CH.sub.3 Ar)--3H at 2.2 ppm (S, CH.sub.3 Ar)--3H at 2.16 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR200##
NMR no. 97-(b): 1H at 10.30 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.30 ppm (Se., HAr 2')--3H at 8.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.70 ppm (M, HAr 5', 6')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.85 ppm (M, CH.sub.2 N.sup. .sym. H.sub.3)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 98-(b): 1H at 9.90 ppm (S, ArNHCO)--1H at 8.66 ppm (D, J=9 Hz, CONH)--1H at 8.28 ppm (S, HAr 2')--5H at 7.70 ppm (M, HAr 5', 6' at CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.68 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.05 ppm (M, ##STR201## 2H at 2.75 ppm (T, J=7 Hz, ##STR202## 6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 99-(b): 1H at 10.5 ppm (S, ArNHCO)--1H at 8.56 ppm (D, J=9 Hz, CONH)--2H at 7.89 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.70 ppm (Se., (CH.sub.2).sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.06 ppm (M, ##STR203## 2H at 2.70 ppm (M, ##STR204## 6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 100-(b): 1H at 12.75 ppm (Se., thiazol NHCO)--1H at 8.90 ppm (D, J=9 Hz, CONH)--4H at 8.15 ppm (M, CH.sub.2 NH.sub.3 and H thiazol in 3)--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.86 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--4 H at 2.5 ppm (M, ##STR205## 2H at 1.90 ppm (M, ##STR206##
NMR no. 101-(b): 1H at 10.8 ppm (S, ArNHCO)--1H at 8.95 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.36 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)-- 3H at 3.80 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR207## 2H at 1.90 ppm (M, ##STR208##
NMR no. 102-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.0 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO) 1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.62 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (De., J=12 Hz, H.sub.2 Eq piperidine)--3H at 3.84 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--2H at 3.58 ppm (M, CH.sub.2 SO and H.sub.6 Eq piperidine)--1H at 3.05 ppm (Te., J= 12 Hz, H.sub.2 Ax piperidine)--1H at 2.81 ppm (Te., J=12 Hz, H.sub.6 Ax piperidine)--1H at 2.60 ppm (M, CHCO.sub.2)--2H at 1.84 ppm (M, H.sub.3 and H.sub.5 piperidine) 2H at 1.50 ppm (M, H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2D, (CH.sub.3).sub.2 C).
NMR no. 103-(b): 1H at 8.72 ppm (D J=9 Hz, CONH)--3H at 8.25 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.75 ppm (M, HAr)--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 104-(b): 2H at 8.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.77 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (M, HAr)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.25 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.58 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 105-(b): 1H at 10.70 ppm (S, ArNHCO)--2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.68 ppm (D, J=9 Hz, CONH)--1H at 8.16 ppm (S, HAr 2')--1H at 7.92 ppm (D, J=8 Hz, HAr 6')--1H at 7.66 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.02 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.90 ppm (M, CH.sub.2 N.sup..sym. HCH.sub.3)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.60 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 106-(b): 1H at 10.80 ppm (S, ArNHCO)--3H at 8.70 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3 et CONH)--2H at 7.92 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.69 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.95 ppm (M, CH.sub. 2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.62 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 107-(b): 1H at 9.95 ppm (S, ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.61 ppm (D, J=8 Hz, HAr 6')--1H at 7.52 ppm (D, J=8 Hz, HAr 4')--1H at 7.31 ppm (T, J=8 Hz, HAr 6')--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)-- 1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.81 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.28 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 108-(b): 1H at 9.75 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (Se., CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 6')--1H at 7.50 ppm (D, J=8 Hz, HAr 4')--1H at 7.25 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.39 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.02 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.69 ppm (T, J=7, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--3H at 2.29 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 109-(b): 1H at 12.7 ppm (Se., NHCO thiazol)--1H at 8.79 ppm (D, J=9 Hz, CONH)--1H at 8.08 ppm (S, H thiazol in 3)--3H at 7.75 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.37 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.68 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.06 ppm (M, CH.sub. 2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.77 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 110-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--5H at 7.96 ppm (M, HAr 2', 6' and CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.55 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 3.25 ppm (Se., NCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 111-(b): 1H at 10.5 ppm (Se., ArNHCO)--1H at 8.95 ppm (D, J=9 Hz, CONH)--2H at 7.89 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.71 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.96 ppm (S, H thiazo)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)-- 2H at 3.05 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.70 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR209## 2H at 1.90 ppm (M, ##STR210##
NMR no. 112-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.17 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.18 ppm (M, H.sub.2 e piperidine) 3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--2H at 3.58 ppm (M, CH.sub.2 SO et H.sub.6 e piperidine)--1H at 3.06 ppm (M, H.sub.2 a piperidine)--1H at 2.75 ppm (M, H.sub.6 a piperidine)--1H at 2.60 ppm (M, H.sub.4 piperidine)--4H at 2.40 ppm (M, ##STR211## 4H at 1.80 ppm et 2H 1.50 ppm ##STR212## et H.sub.3 et H.sub.5 piperidine).
NMR no. 113-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (Se., CHN.sup..sym. H.sub.3)--1H at 8.13 ppm (S, HAr 6')--1H at 8.00 ppm (D, J=8 Hz, HAr 2')--1H at 7.64 ppm (D, J=8 Hz, HAr 3')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1 H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 114-(b): 1H at 8.72 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 8.11 ppm (M, HAr 2', 6')--1H at 7.86 ppm (M, HAr 3')--1H at 6.99 ppm (S, H thiazol)--1H at 6.01 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.89 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.18 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 115-(b): 1H at 10.20 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.16 ppm (Se., HAr 2')--1H at 7.84 ppm (D, J=8 Hz, HAr 6')--3H at 7.66 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.81 ppm (M, CH.sub.2 --N.sup..sym. H.sub.3)--2H at 2.40 ppm (T, J=7 Hz, CH.sub.2 CO.sub.2)--2H at 1.82 ppm (M, CH.sub.2 CH.sub.2 CO.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 116-(b): 1H at 10.3 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--1H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.60 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.79 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.42 ppm (M, CH.sub.2 --CONHAr)--2H at 1.84 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 117-(b): 1H at 10.30 ppm (Se., ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, NHCO)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.72 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.60 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.90 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.36 ppm (M, CH.sub.2 CONHAr)--4H at 1.58 ppm (M, --COCH.sub.2 (CH.sub.2).sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 118-(b): 1H at 12.7 ppm (Se, NHCO thiazol)--1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se, CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.93 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.02 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.02 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.90 ppm (M, CH.sub.2 Gly)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (S, CH.sub.3 thiazol-- 6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 119-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (Se., CH--N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.00 ppm (2M, CHN.sup..sym. H.sub.3)--1H at 2.25 ppm (M, CHCO.sub.2)--4H at 1.80 ppm and 4H at 1.40 ppm (M, CH.sub.2 cyclohexane)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 120-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--2H at 7.80 ppm (Se., HAr 2', 6')--3H at 7.65 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.57 ppm (D, J=8 Hz HAr 4')--1H at 7.47 ppm (T, J=8 Hz, HAr 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 3.00 ppm (M, ##STR213## 6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (D, J=7 Hz, ##STR214##
NMR no. 121-(b): 1H at 10.0 ppm (Se., ArNHCO)--1H at 8.85 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.45 ppm (S, HAr 6')--1H at 7.30 ppm (S, HAr 4')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.43 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.80 ppm (M, CH.sub.2 Gly)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 2.25 ppm (2S, CH.sub.3 Ar)--6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 122-(b): 1H at 10.45 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., N.sup..sym. H.sub.2, piperidine)--1H at 8.20 ppm (Se., N.sup..sym. H.sub.2, piperidine)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1 H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.30 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.90 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--1H at 2.66 ppm (M, CHCONH)--4H at 1.80 ppm (M, CH.sub.2 in .beta.N.sup..sym. H.sub.2 piperisine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 123-(b): 1H at 10.25 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., N.sup..sym. H.sub.2, piperidine)--1H at 8.25 ppm (Se, N.sup..sym. H.sub.2, piperidine)--1H at 8.19 ppm (Se, HAr 2')--1H at 7.86 ppm (D, J=8 Hz, HAr 6')--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.42 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.30 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 Piperidine)--2H at 2.90 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--1H at 2.66 ppm (M, CHCONH)--4H at 1.80 ppm (M, CH.sub.2 in .beta.N.sup..sym. H.sub.2 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 124-(b): 1H at 10.75 ppm (Se., ArNHCO)--1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CHN.sup..sym. H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.00 ppm (M, H.alpha.Ala and CH.sub.2 SO)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.42 ppm (D, J=7 Hz, CH.sub.3 Ala).
NMR no. 125-(b): 1H at 10.80 ppm (Se., ArNHCO)--1H at 9.00 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH--N.sup..sym. H.sub.3)--2H at 7.85 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.75 ppm (D, J=8 Hz, HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.00 ppm (M, H.alpha.Ala and CH.sub.2 SO)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR215## 2H at 1.80 ppm (M, ##STR216## 3H at 1.43 ppm (D, J=7 Hz, CH.sub.3 Ala).
NMR no. 126-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., N.sup..sym. H.sub.3 Ala)--3H at 7.90 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (M, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.50 ppm (D, CH.sub.2 OCO)--1H at 3.15 ppm (M, H.sub.2 a piperidine)--1H at 2.80 ppm (M, H.sub.6 a piperidine)--1H at 2.60 ppm (M, --CHCO.sub.2 piperidine)--2H at 1.80 ppm et 2H at 1.50 ppm (2M, H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (2D, CH.sub.3 CH).
NMR no. 127-(b): 1H at 8.43 ppm (D, J=9 Hz, CONH)--6H at 7.50 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.20 ppm (M, H.sub.2 e piperidine)--1H at 3.90 ppm (D, J=17 Hz CH.sub.2 SO)--1H at 3.64 ppm (M, H.sub.6 e piperidine)--1H at 3.57 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.07 ppm (M, H.sub.2 a piperidine)--2H at 2.96 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 2.75 ppm (M, H.sub.6 a piperidine)--3H at 2.65 ppm (M, CHCO.sub.2 and CH.sub.2 CON)--2H at 1.80 ppm et 2H at 1.50 ppm (H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 128-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--6H at 7.70 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.98 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.18 ppm (H.sub.2 e piperidine)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (M, H.sub.6 e piperidine)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.00 ppm (M, H.sub.2 a piperidine)-- 4H at 2.65 ppm (M, CH.sub.2 N.sup..sym. H.sub.3, H.sub.6 a et H.sub.4 piperidine)--2H at 2.40 ppm (T, CH.sub.2 CON)--4H at 1.70 ppm (M, CHCH.sub.2 CH.sub.2 N.sup..sym. H.sub.3, H.sub.3 and H.sub.5 piperidine)--2H at 1.50 ppm (M, H.sub.3 and H.sub.5 piperidine)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 129-(b): 1H at 8.50 ppm (Se., N.sup..sym. H.sub.2 piperidinium)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 8.25 ppm (Se., N.sup..sym. H.sub.2 piperidinium)--3H at 7.40 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (M, H.sub.2 e piperidine)--2H at 3.90 ppm (M, H.sub.6 e piperidine and CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.25 ppm (M, H.sub.2 e and H.sub.6 e piperidinium)--1H at 3.15 ppm (M, H.sub. 2 a piperidine)--3H at 2.85 ppm (M, H.sub.6 a piperidine and H.sub.2 a and H.sub.6 a piperidinium)--2H at 2.70 ppm (M, H.sub.4 piperidine and H.sub.4 piperidinium)--6H at 1.75 ppm and 2H at 1.50 ppm (2M, H.sub.3 and H.sub.5 piperidinium H.sub.3 and H.sub.5 piperidine)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 130-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--2H at 7.45 ppm (M, HAr 3', 5') 1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.45 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 131-(b): 1H at 8.85 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--2H at 7.45 ppm (M, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.73 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (S, CH.sub.3 Ar)--4H at 2.40 ppm (M, ##STR217## 2H at 1.80 ppm (M, ##STR218##
NMR no. 132-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.55 ppm (S, HAr)--1H at 7.45 ppm (S, HAr)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.83 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 3.70 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.40 ppm (S, CH.sub.3 Ar)-- 3H at 2.34 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 133-(b): 1H at 12.5 ppm (Se., ArNHCO)--1H at 8.78 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (Se., ##STR219## 1H at 8.20 ppm (S, H thiazol in 3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (M, ##STR220## 1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.40 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 134-(b): 1H at 8.85 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (S, H thiazol in 3)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 3.20 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 135-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--1H at 8.57 ppm (S, H thiazol in 3)--3H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.45 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 136-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S, H thiazol in 3)--1H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.45 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR221## 2H at 1.86 ppm (M, ##STR222##
NMR no. 137-(b): 1H at 8.90 ppm (T, J=8 Hz, ##STR223## 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.88 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.40 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.40 ppm (D, J=8 Hz, ArCH.sub.2 NH)--1H at 4.06 ppm 1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 S.fwdarw.O)--2H at 3.57 ppm (M, OCCH.sub.2 N.sup..sym. H.sub.3)--2H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
By operating as in Example 2 of Example 3, the compounds according to the invention are obtained, in the form of trifluoroacetates described in Table II below. ##STR224##
These compounds are identified by a reference number and for each of them are given the values of R.sub.1, R.sub.2, n and B and the NMR spectrum.
The chromatography eluant is also given which serves to isolate (V): the last intermediate product before deblocking of the acid and amine functions of the molecule. This intermediate V is characterized by its infra-red spectrum, the wavelengths indicated in cm.sup.-1 correspond in order to the elongation vibration frequencies of the carbonyl at the 8 position of the beta lactam, the tertiobutylic esters and the thioester at the 3 position, the amide at the 7 position and the protective carbonate of the amine. When 2 wavelengths only are indicated the second corresponds to a wide band which covers the elongation vibration frequencies both of the esters, the amide and the protective carbonate of the amine and the thioester.
It happens for certain products that the vibration frequency of the thioester is at the same wavelength as that of the tertiobutylic esters. This is indicated in the table by +COS opposite the corresponding vibration frequency.
NMR Spectra: The spectra are recorded at 60 MHz, indicated by (a) or at 250 MHz, indicated by (b); when two stereoisomers exist in the molecule, the split signals are indicated by *.
NMR no. 1-(a): 8H between 6 and 9 ppm (wide signal, CH.sub.2, TFA, CO.sub.2 H)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.86 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--4H at 2.75 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 COS)--2H at 1.77 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 2-(a): 8H between 6.5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.88 ppm (S, H thiazol)--1H at 6.0 ppm (D D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J=13 Hz, CH.sub.2 SCO)--3H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 SCO)--4H at 2.65 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 COS)--10H 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 3-(a): 8H between 6.5 et 8.7 ppm (wide signal (NH.sub.2, CO.sub.2 H, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J.sub.1 =4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J=13 Hz, CH.sub.2 SO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--4H at 2.80 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 CO) 12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2).
NMR no. 4-(a): 7H between 6.5 et 9.5 ppm (Wide signal, NH.sub.2, NH, CO.sub.2 H, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--5H at 3.0 ppm (M, CH.sub.2 N and CHCOS)--4H at 1.90 ppm (M, CH.sub.2 CH.sub.2 N)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 5-(b): 5H between 7 and 9 ppm (wide signal, NH.sub.2, TFA, NH)--1H at 8.34 ppm (2D, J=9 Hz, CONH)*--1H at 6.8 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (2D, J=13 Hz, CH.sub.2 SCO)*--1H at 3.76 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.66 ppm (S, CH.sub.2 SO)--1H at 3.4 ppm, 1H at 3.16 ppm and 2H at 2.95 ppm (M, CH.sub.2 N)--1H at 2.80 ppm (M, CHCOS)--4H between 1.5 and 2.1 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 N)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 6-(a): 3H at 8.50 ppm (S.e., CONH, N.sup.+ H.sub.2)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.85 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--1H at 3.80 ppm B of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--2H at 3.70 ppm (S.e., CH.sub.2 SO)--7H at 2.50 ppm (M, CH.sub.3 NH, CH.sub.2 NH, ##STR292## 2H at 1.80 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 7-(a): 1H at 8.35 ppm (D, J=9 Hz, CONH)--8H between 6.5 and 10 ppm (CO.sub.2 H, NH.sub.2, TFA)--1H at 6.82 ppm (S, H thiazol)--1H at 6,00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.66 ppm (M, CH.sub.2 SO and B of AB, CH.sub.2 SCO)--4H at 2.65 ppm (M, CH.sub.2 CO and CH.sub.2 NH.sub.2)--6H at 1.42 ppm (S, (CH.sub.3).sub.2 C)--10H at 1.25 ppm (S.e., (CH.sub.2).sub.5 CH.sub.2 NH.sub.2).
NMR no. 8-(b): 1H at 8.34 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.14 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.69 ppm (D, J=13 Hz, CH.sub.2 SO)--2H at 3.63 ppm (S, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.45 ppm (M, CHCOS)--4H at 1.84 ppm (M, CH.sub.2 CHCOS)--6H at 1.44 ppm (2 S, (CH.sub.3).sub.2 C)--2H at 1.40 ppm and 2H at 1.0 ppm (M, CH.sub.2 CHCH.sub.2 NH.sub.2). NMR no. 9-(b): 1H at 8.36 ppm (D, J=9 Hz, NHCO)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.40 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--6H at 1.42 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 10-(a): 1H at 8.30 ppm (D, J=9 Hz, CONH)--8H between 6.5 and 9 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 4.90 ppm (D, J=4 Hz H.sub.6)--1H at 4.25 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--1H at 3.90 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--2H at 3.65 ppm (S.e., CH.sub.2 SO)--10H between 1 and 2.3 ppm (M, ##STR293## 6H at 1.43 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 11-(b): 1H at 8.79 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm and 1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.84 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.90 ppm (D, J=4 hz, H.sub.6)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 4.15 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.54 ppm (S, CH.sub.2 SO)--2H at 3.20 ppm and 3H at 2.90 ppm (M, CH.sub.2 NH and CHCOS)--2 H at 1.95 ppm et 2H at 1.65 ppm (M, CH.sub.2 CH.sub.2 NH).
NMR no. 12-(b): 2H at 8.60 ppm (M, CONH, N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.81 ppm (2S, H thiazol)*--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (2D superposed, H.sub.6)*--1H at 4.60 ppm (Q, J=7 Hz, CHON)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.65 ppm (S, CH.sub.2 SO)--2H at 3.25 ppm and 3H at 2.95 ppm (M, CHCOS and ##STR294## 2H at 1.95 ppm et 2H at 1.70 ppm (M, ##STR295## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 13-(b): 2H at 8.70 ppm (M, CONH and N.sup.+ H.sub.2)--1H at 8.40 ppm (M, N.sup.+ H.sub.2)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.70 ppm (S, CH.sub.2 SO)--2H at 3.25 ppm (M, CH.sub.2 NH)--3H at 2.90 ppm (M, CH.sub.2 NH and CHCOS)--4H at 2.40 ppm (M, ##STR296## 6H at 1.80 ppm (M, ##STR297##
NMR no. 14-(b): 1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, H ortho CO)--2H at 7.56 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.88 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 4.37 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.13 ppm (M, CH.sub.2 NH.sub.2)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO).
NMR no. 15-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, H ortho CO)--2H at 7.56 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, superposed, H.sub.6)*--1H at 4.60 ppm (Q, J=7 Hz, CHON)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.13 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (S, CH.sub.2 SO)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 16-(b): 1H at 8.61 ppm (D, J=9 Hz, CONH)--5H at 8.40 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--2H at 7.95 ppm (D, J=8 Hz, H ortho CO)--2H at 7.61 ppm (D, j+8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (S.e., CH.sub.2 NH.sub.2)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--4H at 2.35 ppm (M, ##STR298## 2H at 1.85 ppm (M, ##STR299##
NMR no. 17-(b): 1H at 8.62 ppm (D, J=9 Hz, CO NH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.00 ppm (Se., HAr 2')--1H at 7.90 ppm (D, J=8 Hz, HAr 6')--1H at 7.72 ppm (D, J=8 Hz, HAr 4')--1H at 7.55 ppm (T, J=8 Hz, HAr 5')--1H at 6.93 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz H.sub.6)--1H at 4.43 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 18-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.00 ppm (Se., HAr 2')--1H at 7,90 ppm (D, J=8 Hz, HAr 6')--1H at 7.72 ppm (D, J=8 Hz, HAr 4')--1H at 7.55 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.44 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.77 ppm (Se., CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR300## 2H at 1.90 ppm (M, ##STR301## NMR no. 19-(b): 2H at 8.80 ppm (Se., N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2',6')--2H at 7.60 ppm (D, J=8 Hz, Ar 3', 5')--1H at 6.94 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.16 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (T, J=7 Hz CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 20-(b): 1H at 8.84 ppm (D, J=9 Hz, CONH)--2H at 8.80 ppm (Se., N.sup..sym. H.sub.2 --CH.sub.3)--2H at 7.95 ppm (D, J=8 Hz, HAr, 2', 6')--2H at 7.60 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.16 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--4H at 2.40 ppm (M, ##STR302## 2H at 1.90 ppm (M, ##STR303##
NMR no. 21-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (M, HAr 4', 6')--1H at 7.37 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.96 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.39 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.07 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.78 ppm (S, CH.sub.2 SO)--3H at 2.26 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 22-(b): 1H at 8.89 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (M, HAr 4', 6')--1H at 7.37 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.79 ppm (S, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR304## 3H at 2.25 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR305##
NMR no. 23-(b): 1H at 8.64 ppm (D, J=9 Hz, CONH)--3H at 8.14 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.95 ppm (S, HAr 2')--1H at 7.60 ppm (D, J=8 Hz, HAr 6')--1H at 7.39 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.37 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.08 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub. 2 SCO)--2H at 3.74 ppm (Se., CH.sub.2 SO)--3H at 2.37 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 24-(b): 1H at 8.80 ppm (2D, J=9 Hz CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.94 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--1H at 7.39 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (2S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (M, CH.sub.3 CHON)--1H at 4.37 ppm (2D, J=13 Hz, CH.sub.2 SCO)--2H at 4.08 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.73 ppm (Se., CH.sub.2 SO)--3H at 2.36 ppm (S, ArCH.sub.3)--3H at 1.42 ppm (D, J=7 Hz, CH.sub.3 CHON).
NMR no. 25-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.17 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.50 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.06 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--3H at 2.46 ppm (S, ArCH.sub.3)--6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 26-(b): 1H at 8.80 ppm (2D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.46 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (2S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (M, CH.sub.3 CH--ON)--1H at 4.40 ppm (2D, J=13 Hz, CH.sub.2 SCO)--2H at 4.06 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.76 ppm (Se., CH.sub.2 SO)--3H at 2.40 ppm (S, ArCH.sub.3)--3H at 1.44 pm (D, J=7 Hz, CH.sub.3 CHON).
NMR no. 27-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.18 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.78 ppm (D, J=13 Hz, CH.sub.2 SO)--2H at 3.69 ppm (Se., CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 --C--O)--6H at 1.22 ppm (S, (CH.sub.3).sub.2 CCOS).
NMR no. 28-(b): 1H at 10.80 ppm (S, ArNHCO)--1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.89 ppm (D, J=8 Hz HAr 2', 6')--2H at 7.74 ppm (D, J=8 Hz HAr 3', 5')--1H at 6.96 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.88 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup. .sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 29-(b): 1H at 10.83 ppm (S, ArNHCO)--1H at 8.89 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.71 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.87 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup. .sym. H.sub.3)--4H at 2.40 ppm (M, ##STR306## 2H at 1.90 ppm (M, ##STR307##
NMR no. 30(b): 1H at 8.50 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.20 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.36 ppm (D, J=9 Hz, CONH)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.72 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.14 ppm (S, CH.sub.2 SO)--2H at 3.17 ppm 2H at 2.80 ppm (M, 6H .sub.2 in .alpha. N.sup..sym. H.sub.2)--2H at 2.55 ppm (D, J= 7 Hz CH.sub.2 COS)--1H at 2.00 ppm (M, CHCH.sub.2 COS)--2H at 1.75 ppm and 2H 1.30 ppm (M, CH.sub.2 in .beta. N.sup..sym. H.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 31-(b): 1H at 8.34 ppm (D, J=9 Hz, CONH)--3H at 7.92 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.30 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.26 ppm (DE, J=12 Hz, H.sub.2 Eq piperidine)--1H at 4.15 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.84 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.72 ppm (D, J=13 Hz, CH.sub.2 SCO)--3H at 3.60 ppm (M, CH.sub.2 SO+H.sub.6 Eq piperidine)--1H at 3.05 ppm (TE, J=12 Hz, H.sub.2 Ax piperidine)--1H at 2.87 ppm (TE, CHCOS)--H at 2.74 ppm (TE, J=12 Hz, H.sub.6 Ax piperidine)--2H at 1.86 ppm (M, H en 3 in 5 piperidine)--2H at 1.45 ppm (M, H en 3 and 5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 32-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.30 ppm (Se., --N.sup..sym. H.sub.3 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.26 ppm (De., J=12 Hz, H.sub.2 Eq piperidine)--1H at 4.16 (D, J=13 Hz, CH.sub.2 SCO)--2 H at 3.82 ppm (M, CH.sub.2 Gly)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SO)--3H at 3.63 ppm (Se., CH.sub.2 SOH.sub.6 Eq piperidine)--1H at 3.05 ppm (Te., J=13 Hz, H.sub.2 Ax piperidine)--1H at 2.87 ppm (Te., J=12 Hz, ##STR308## 1H at 2.75 ppm (Te., J=12 Hz, H.sub.6 Ax piperidine)--4H at 2.44 ppm (M, ##STR309## 4H at 1.90 ppm (M, ##STR310## and H.sub.3 Eq and H.sub.5 Eq piperidine)--2H at 1.50 ppm (M, H.sub.3 Ax and H.sub.5 Ax piperidine).
NMR no. 33-(b): 1H at 10.70 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.30 ppm (S, HAr 2')--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 H, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)-- 1 H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.75 ppm (M, CH.sub.2 SO and CH.sub.2 Gly)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 34-(b): 1H at 10.65 ppm (Se., ArNHCO)--1H at 8.80 ppm (D, J=9 Hz, NHCO)--1H at 8.25 ppm (Se., HAr 2')--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--1H at 7.58 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--1 H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.75 ppm (M, CH.sub.2 SO and CH.sub.2 Gly)--4H at 2.40 ppm (M, ##STR311## 2H at 1.90 ppm (M, ##STR312##
NMR no. 35-(b): 1H at 8.40 ppm (D, J=9 Hz, CONH)--6H at 7.60 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.30 ppm (M, H.sub.2 e piperidine)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.60 ppm (S, CH.sub.2 SO)--1H at 3.55 ppm (M, H.sub.6 e piperidine)--4H at 2.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et H.sub.2 a and H.sub.6 a piperidine)--3H at 2.60 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3 H.sub.4 piperidine)--2H at 1.80 ppm et 2H at 1.50 ppm (2M, H.sub.3 at H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 36-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--2H at 7.43 ppm (M, HAr 3', 5')--1H at 6.98 ppm (Se., H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.34 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.77 ppm (Se., CH.sub.2 SO--1H at 2.34 ppm (S, CH.sub.3 Ar)--6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 37-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.72 ppm (D, J=8 Hz, HAr 6')--2H at 7.40 ppm (M, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz, H.sub.6)--1H at 4.34 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.78 ppm (Se., CH.sub.2 SO)--2H at 2.34 ppm (S, CH.sub.3 Ar)--4H at 2.30 ppm (M, ##STR313## 2H at 1.80 ppm (M, ##STR314##
NMR no. 38-(b): 1H at 8.60 ppm (D, J=9 Hz, CONH)--7H at 7.70 ppm (M, HAr et CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.38 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 3.00 ppm (M, CHCH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.19 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 39-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--7H at 7.80 ppm (M, HAr et N.sup..sym. H.sub.3 CH.sub.2)--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.93 ppm (D, J=13 Hz CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 3.00 ppm (M, CHCH.sub.2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR315## 2H at 1.85 ppm (M, ##STR316## 3H at 1.25 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 40-(b): 1H at 12.6 ppm (Se., ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.00 ppm (S, H thiazol in 3)--3H at 7.75 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.78 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.50 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.80 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 41-(b): 1H at 12.8 ppm (Se., NHCOCH.sub.2)--1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.25 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.16 ppm (S, H thiazol in 3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.96 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO) 3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 42-(b): 1H at 10.6 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (M, HAr 2', 6')--5H at 7.60 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.72 ppm (M, CH.sub.2 CH.sub.2 N.sup.+ H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 43-(b): 1H at 10.5 ppm (S, ArNHCO)--1H at 8.85 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm et 2H at 7.75 ppm (M, HAr)--3H at 7.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.45 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.86 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.02 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.72 ppm (M, CH.sub.2 CH.sub. 2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR317## 2H at 1.85 ppm (M, ##STR318##
NMR no. 44-(b): 1H at 10.9 ppm (S, ArNHCO)--2H at 8.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3 at CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (M, CH.sub.3 N.sup..sym. H.sub.2 --CH.sub.2) 6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 45-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.55 ppm (D, H thiazol in 3)--3H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.95 ppm (D of D J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--2H at 4.46 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.30 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.73 ppm (Se., CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 46-(b): 1H at 8.87 ppm (T, J=8 Hz, NHCH.sub.2 Ar)--1H at 8.64 ppm (D, J=9 Hz, NHCO)--3H at 8.00 ppm (Se., H.sub.3 N.sup..sym. CH.sub.2)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.42 ppm (D, J=8 Hz, HAr3', 5')--1H at 6.94 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D of D, J=4 Hz, H.sub.6)--3H at 4.40 ppm (M, ArCH.sub.2 NH et CH.sub.2 SCO)--1H at 3.88 ppm D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm) (Se., CH.sub. 2 S.fwdarw.O)--2H at 3.58 ppm (M, OCCH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
The products of the invention have been studied as regards their pharmacological properties and, more especially, bacteriostatic action. This has been determined in vitro by the dilution method, and the study was on Gram negative strains.
Results, expressed in minimum inhibiting concentrations (MIC-- .mu.g/ml), are collected in the following table (Table III).
The results presented in Table III show good activity on Gram negative bacteria of the products according to the invention.
To evaluate the stability of these products towards beta-lactamases, their MIC was determined on isogenic strains producing and not producing beta-lactamases.
The results are expressed in .mu.g/ml in Table IV.
According to the results of table IV, the products according to the invention have an equal or comparable activity on strains producing or not producing beta-lactamases, which shows the good stability towards beta-lactamases.
The therapeutic effectiveness of the products was determined on the septicemic model of the mouse. the septicemia was initiated by the intraperitoneal innoculation of 0.5 ml of a suitable dilution of a suspension of the Escherichia coli SOL 90 strain. The products were administered in solution in a phosphate buffer pH 7.0 in a volume of 0.2 ml sub-cutaneously to batches of 10 mice, 1 to 5 hours after innoculation of the microorganism. After 4 days of observation in the course of which the mortality was noted, the 50% effective doses (DE 50) were calculated by the Muench and Reed method.
The results obtained are shown in Table V.
According to the results of table V, the products, according to the invention, show good IN VIVO therapeutic activity.
In addition, according to tests carried out up till now on animals, the toxicity of the products according to the invention has appeared to be sufficiently low to enable their use in therapeutics.
The products of the invention can hence be employed as antibiotics in human or veterinarian medicine. They have a wide spectrum on Gram negative organisms and can be used in all germ sensitive bacterial infections.
The products can be administered by the general route (parenteral, oral or topically).
The pharmaceutical compositions are produced from the compounds (I) in soluble forms obtained by salification of one of the acid functions of the molecule or of one of the amine functions of the B chain.
The pharmaceutical compositions can be solid or liquid and be presented, for example, in the form of injectable preparations, tablets, gelules, granules, pommades, creams, gels or suppositories. The posology can vary within wide proportions, in particular according to the type and seriousness of the infection to be treated and according to the mode of administration. Mostly, in the adult, by the injectable route, it is comprised between 0.250 g and 4 g per day.
By way of example of pharmaceutical composition, there may be prepared injectable solutions of the sodium salt of SR 41 973:
To a solution of 3 g of dihydrochloride of SR 41 973 in 25 ml of water, is added drop by drop a saturated solution of sodium bicarbonate. When the pH is 3, the solution is filtered. The pH is then adjusted to 3.6 by the addition of some drops of saturated solution of sodium bicarbonate. The solution is cooled to +4.degree. C. and the SR 41 973 starts to crystallize. 75 ml of acetone are added slowly drop by drop. After 1/2 hour of stirring at +4.degree. C., the crystals are filtered and washed twice with a mixture (1-1) of water and acetone and finally washed twice with 20 ml of acetone. The product is dried in the dessicator over P.sub.2 O.sub.5. 1.9 g of the compound SR 41 973 is obtained.
1.25 g of the SR 41 973 so obtained is suspended in 15 ml of water at +4.degree. C. A solution of 0.168 g of sodium bicarbonate in 3 ml of water is added drop by drop. The clear solution thus obtained is frozen and freeze-dried, after sterile filtration, to obtain the sodium salt of 41 973 ready for injection.
Claims
We claim:
1. Cephalosporin compounds of the formula: ##STR319## in which: the COOA group at the 4 position is an acid radical, or an alkali or alkaline-earth metal salt or an amino acid or amine salt, or an ester radical easily hydrolyzable or metabolically labile and pharmaceutically acceptable, X denotes an oxygen atom or a sulfur atom, n is zero or 1, R.sub.1 and R.sub.2 each denote, independently, hydrogen or a lower alkyl group, or R.sub.1 and R.sub.2 taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl nucleus, B is the residue of a primary or secondary amine selected from the group consisting of Z--NH--R where Z is a straight or branched chain alkylene group having from 2 to 7 carbon atoms, optionally interrupted by a sulfur atom and optionally substituted by a hydroxyl, thiol, methylthio, amino acetamido, carbamoyl, phenyl, hydroxyphenyl or imidazoyl group, a cyclopentylidene or cyclohexylidene group, R represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms, Z'--Alk--NH--R where Z' represents a 1,2-phenylene or 1,3-phenylene or 1,4-phenylene group optionally substituted by a halogen atom or by 1 or 2 methoxy groups or by 1, 2 or 3 methyl groups or Z' represents a 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene group, Alk represents a straight or branched alkyl group having from 1 to 3 carbon atoms, ##STR320## where Z' is as defined above, Y denotes an alkyl (CH.sub.2).sub.m group in which m=0, 1, 2, 3 or 4, or a branched alkyl group having 2 or 3 carbon atoms or Y with NH--R" constitutes a ring ##STR321## R' and R", identical or different, having the same meaning as that given for R above, Z"--NH--R where Z" is a 1,3-cyclohexylene or 1,4-cyclohexylene group and R is as previously defined, ##STR322## where R.sub.3 represents a hydrogen atom or a methyl group, n=0 or 1 and Alk and R are as previously defined, a 2-piperidyl, 3-piperidyl or 4-piperidyl group optionally substituted on the nitrogen atom by a --CO--Alk--NH.sub.2 or a ##STR323## group where Alk is as previously defined, and the salts of said compounds with pharmaceutically acceptable acids.
2. Compounds according to claim 1, which are in one of the syn and anti forms.
3. Pharmaceutical composition with bacteria-static action containing, as active ingredient, a compound according to claim 1 in combination with a pharmaceutically acceptable vehicle.
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