US 3,962,252 AGrant
10-Imidoylacridans
Issue Date:1976-06-08
•7 Claims
Abstract
Novel 10-imidoylphenoxazines and 10-imidoylacridans are prepared by reacting a phenoxazine or acridan having optional substituents selected from the group consisting of trifluoromethyl, halogen, dihalogen, alkyl or alkoxy with an imidoyl halide prepared in situ from amides and lactams. Illustrative embodiments are 10-(5-methyl-1-pyrrolin-2-yl)phenoxazine and 9,9-dimethyl-10-(5-methyl-1-pyrrolin-2-yl)acridan. The imidoylphenoxazine and imidoylacridan products are generally useful as smooth muscle relaxants.
Metadata
Assignee
- Mead Johnson & Company
Inventors
- Yao Hua Wu
- Walter G. Lobeck, Jr.
Application Information
Application Number:US 5614627
Filing Date:1975-03-24
Priority Date:1973-02-28
Art Unit:122
Classifications
IPC:
C07D21914C07D40104
Field of Search:
260279 R;240 G
Patent Drawings
This patent does not have any drawings.
Description
Example 1
Phosphorus oxychloride (3.8 g., 0.025 mole) is added in one portion to a mixture of phenoxazine (4.6 g., 0.025 mole) and 2-pyrrolidinone (2.1 g., 0.025 mole) in 50 ml. of 1,2-dichloroethane at 25.degree.C. After stirring the reaction mixture for 15 hr., the reaction mixture is quenched in a mixture of 30 ml. of 5N sodium hydroxide and 30 g. of crushed ice. The organic layer is separated, extracted with 100 ml. of 1.5N hydrochloric acid, made basic with sodium hydroxide and extracted with ether. After drying the ethereal extract over magnesium sulfate and concentrating, the residue thus obtained is crystallized from n-heptane to provide 4.2 g. of 10-(1-PYRROLIN-2-YL)PHENOXAZINE free base, m.p. 110.degree.-113.degree.C. The free base taken up in ethanol, acidified with ethanolic hydrogen chloride and diluted with ether provides a 37% yield of 10-(1-PYRROLIN-2-YL)PHENOXAXINE HYDROCHLORIDE as a monohydrate, m.p. 214.degree.-217.degree.C. (corr.).
Analysis. Calcd. for C.sub.16 H.sub.14 N.sub.2 O.sup.. HCl.sup.. H.sub.2 O (percent): C, 63,05; H, 5.62; N, 9.19; Cl, 11.64. Found (percent): C, 62.92; H, 5.66; N, 9.35; Cl, 11.34.
NMR delta (ppm) (DMSO-D.sub.6, TMS reference): 2.13m, 3.27t(7.2), 3,38s, 3.75t (7.0), 7.3m, 7.7m, 10.63bs.
Example 2
Reaction of phenoxazine with 5-methyl-2-pyrrolidinone according to the procedure of Example 1 affords the free base 10-(5-METHYL-1-PYRROLIN-2-YL)PHENOXAZINE, m.p. 135.degree.-137.degree.C., from n-heptane. Conversion of the free base to the hydrochloride salt provides 10-(5-METHYL-1-PYRROLIN-2-YL)PHENOXAZINE HYDROCHLORIDE, m.p. 229.5.degree.-236.0.degree.C. (dec.) (corr.), in a 57% overall yield.
Analysis. Calcd. for C.sub.17 H.sub.16 N.sub.2 O.sup.. HCl (percent): C, 67.88; H, 5.70; N, 9.32; Cl, 11.78. Found (percent): C, 67.79; H, 5.71; N, 9.39; Cl, 11.75.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.57d(6.3), 2.22m, 3,27m, 4.54m, 7.2m, 7.8m, 11.65bs.
Example 3
Reaction of phenoxazine, 5,5-dimethyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-(5,5-DIMETHYL-1-PYRROLIN-2-YL)-PHENOXAZINE, m.p. 148.degree.-150.degree.C. Conversion of the free base to the hydrochloride salt affords 10-(5,5-DIMETHYL-1-PYRROLIN-2-YL)PHENOXAZINE HYDROCHLORIDE, m.p. 239.degree.-242.5.degree.C. (corr.), in a 48% overall yield.
Analysis. Calcd. for C.sub.16 H.sub.18 N.sub.2 O.sup.. HCl (percent): C, 68.67; H, 6.08; N, 8.90; Cl, 11.27. Found (percent): C, 68.50; H, 6.21; N, 8.75; Cl, 11.24.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.69s, 2.05t (7.5), 3.26t (7.5), 7.2m, 7.8m, 11.80bs.
Example 4
Reaction of 2-(trifluoromethyl)phenoxazine, 2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-(1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE as a distillable oil, b.p. 140.degree.-146.degree.C. at 0.1 mm Hg. Conversion of the free base to the hydrochloride salt affords 10-(1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE HYDROCHORIDE, m.p. 219.5.degree.-222.5.degree.C. (dec.)(corr.), in a 62% overall yield by triturating with warm benzene.
Analysis. Calcd. for C.sub.17 H.sub.13 F.sub.3 N.sub.2 O.sup.. HCl (percent): C, 57.55; H, 3.98; N, 7.90; Cl, 9.99. Found (percent): C, 57.60; H, 4.14; N, 7.63; Cl, 9.77.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 2.27m, 3.31t (7.4), 4.11t (7.0), 7.2m, 7.9m.
Example 5
Reaction of 2-(trifluoromethyl)phenoxazine, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-(5-METHYL-1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE as a distillable oil, b.p. 145.degree.-152.degree.C. at 0.03 mm Hg. Conversion of the free base to the hydrochloride salt affords 10-(5-METHYL-1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE HYDROCHLORIDE, m.p. 192.5.degree.-195.5.degree.C. (dec.)(corr.)., in a 45% overall yield.
Analysis. Calcd. for C.sub.18 H.sub.15 F.sub.3 N.sub.2 O.sup.. HCl (percent): C, 58.62; H, 4.37; N, 7.60; Cl, 9.61. Found (percent): C, 58.61; H, 4.42; N, 7.41; Cl, 9.31.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.57d (6.2), 1.97m, 3.26m, 4.54m, 7.3m, 8.0m.
Example 6
Reaction of 2-(trifluoromethyl)phenoxazine, 5,5-dimethyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-(5,5-DIMETHYL-1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE, m.p. 64.degree.-67.degree.C. Conversion of the free base to the hydrochloride salt affords 10-(5,5-DIMETHYL-1-PYRROLIN-2-YL)-2-(TRIFLUOROMETHYL)PHENOXAZINE HYDROCHLORIDE, m.p. 204.5.degree.-207.5.degree.C. (dec.) (corr.), in a 30% overall yield.
Analysis. Calcd. for C.sub.19 H.sub.17 F.sub.3 N.sub.2 O.sup.. HCl (percent): C, 59.61; H, 4.74; N, 7.32; Cl, 9.26. Found (percent): C, 59.37; H, 4.78; N, 7.12; Cl, 9.11.
NMR delta (ppm) (CDCl.sub.3, TMS reference): 1.70s, 2.10t (7.5), 3.27t (7.5), 7.4m, 12.00bs.
Example 7
Reaction of 2-chlorophenoxazine, 2-pyrrolidinone, and phosphorus oxychloride according to the procedure of Example 1 provides the free base 2-CHLORO-10-(1-PYRROLIN-2-YL)PHENOXAZINE as a distillable oil, b.p. 150.degree.-165.degree.C. at 0.1 mm Hg. Conversion of the free base to the hydrochloride salt affords 2-CHLORO-10-(1-PYRROLIN-2-YL)-PHENOXAZINE HYDROCHLORIDE, m.p. 209.5.degree.-213.5.degree.C. (corr.), in a 40% overall yield.
Analysis. Calcd. for C.sub.16 H.sub.13 ClN.sub.2 O.sup.. HCl (percent): C, 59.82; H, 4.39; N, 8.72; Cl, 22.09. Found (percent): C, 59.71; H, 4.44; N, 8.50; Cl, 21.97.
NMR delta (ppm)(DMSO-d.sub.6, TMS reference): 2.13m, 3.27t (7.5), 3.75t (7.0), 7.3m, 7.7m, 10.67bs.
Example 8
Reaction of 2-chlorophenoxazine, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 2-CHLORO-10-(5-METHYL-1-PYRROLIN-2-YL)-PHENOXAZINE as a distillable oil, b.p. 150.degree.-170.degree.C. at 0.1 mm Hg. Conversion of the free base to the hydrochloride salt affords 2-CHLORO-10-(5-METHYL-1-PYRROLIN-2-YL)PHENOXAZINE HYDROCHLORIDE, m.p. 213.5.degree.-215.5.degree.C., as a crystalline solid in a 34% overall yield by refluxing with benzene.
Analysis. Calcd. for C.sub.17 H.sub.15 ClN.sub.2 O.sup.. HCl (percent): C, 60.90; H, 4.81; N, 8.36; Cl, 21.16. Found (percent): C, 60.79; H, 5.01; N, 8.28; Cl, 20.78.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.58d (6.2), 2.23m, 3.34m, 4.58m, 7.2m, 7.8m, 12.03bs.
Example 9
Reaction of 2-chlorophenoxazine, 5,5-dimethyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides 2-CHLORO-10-(5,5-DIMETHYL-1-PYRROLIN-2-YL)-PHENOXAZINE, m.p. 118.degree.-120.degree.C., from ethanol.
Analysis. Calcd. for C.sub.18 H.sub.17 ClN.sub.2 O (percent): C, 69.11; H, 5.48; N, 8.96; Cl, 11.34. Found (percent): C, 68.89; H, 5.41; N, 8.85; Cl, 11.01.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.28s, 1.78t (7.5), 2.81t (7.5), 6.9m, 7.25m, 7.53dd (1.8, 0.5).
Example 10
Reaction of 4-chlorophenoxazine, 5-methyl 2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 4-CHLORO-10-(5-METHYL-1-PYRROLIN-2-YL)PHENOXAZINE, m.p. 120.degree.-122.degree.C., from ethanol. Conversion of the free base to the hydrochloride salt affords 4-CHLORO-10-(5-METHYL-1-PYRROLIN-2-YL)PHENOXAZINE HYDROCHLORIDE, m.p. 228.degree.-230.degree.C., (dec.) (corr.), by trituration with hot benzene.
Analysis. Calcd. for C.sub.17 H.sub.15 ClN.sub.2 O.sup.. HCl (percent): C, 60.90; H, 4.81; N, 8.36; Cl, 21.16. Found (percent): C, 60.85; H, 4.90; N, 8.22; Cl, 20.94.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.57d (6.4), 2.17m, 3.30m, 4.60m, 7.3m, 7.9m, 11.70bs.
Example 11
Reaction of 2-methoxyphenoxazine, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 2-METHOXY-10-(5-METHYL-1-PYRROLIN-2YL)PHENOXAZINE as an oil. Conversion of the free base to the hydrochloride salt affords 2METHOXY-10-(5-METHYL-1-PYRROLIN-2-YL)-PHENOXAZINE HYDROCHLORIDE, m.p. 223.5.degree.-224.5.degree.C. (dec.)(corr.), as the hemihydrate by trituration with acetone.
Analysis. Calcd. for C.sub.18 H.sub.18 N.sub.2 O.sub.2.sup.. HCl.sup..1/2 H.sub.2 O (percent): C, 63.62; H, 5.92; N, 8.25; Cl, 10.42. Found (percent): C, 63.96; H, 6.40; N, 7.99; Cl, 10.05.
NMR delta (ppm)(D.sub.2 O, HDO reference): 1.18d, (6.1), 2.18m, 2.77m, 3.81s, 3.95m, 7.1m.
Example 12
Reaction of phenoxazine, 2-piperidone, and phosphorus oxychloride according to the procedure of Example 1 provides 10-(3,4,5,6-TETRAHYDRO-2-PYRIDYL)PHENOXAZINE HYDROCHLORIDE, m.p. 218.5.degree.-221.degree.C. (corr.), in a 27% overall yield from absolute ethanol.
Analysis. Calcd. for C.sub.17 H.sub.16 N.sub.2 O.sup.. HCl (percent): C, 67.88; H, 5.70; N, 9.30; Cl, 11.78. Found (percent): C, 67.51; H, 5.68; N, 9.19; Cl, 11.69.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.87m, 2.84m, 3.83m, 7.2m, 7.7m, 10.77bs.
Example 13
Reaction of acridan, 2pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-[2-(1-PYRROLINYL)]ACRIDAN, m.p. 130.degree.-132.degree.C., from n-heptane. Conversion of the free base of the hydrochloride salt affords 10-[2-(1-PYRROLINYL)]ACRIDAN HYDROCHLORIDE as the hemihydrate, m.p. 251.degree.-252.degree.C. (dec.)(corr.), from ethanol-ether in a 42% overall yield.
Analysis. Calcd. for C.sub.17 H.sub.16 N.sub.2.sup.. HCl.sup..1/2 H.sub.2 O (percent): C, 69.50; H, 6.18; N, 9.53; Cl, 12.07. Found (percent): C, 69.74; H, 6.29; N, 9.50; Cl, 12.17.
NMR delta (ppm)(D.sub.2 O, HDO reference): 2.25m, 3.05m, 3.57s, 3.86t (7.0), 7.4m.
Example 14
Reaction of acridan, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-[2-(5-METHYL-1-PYRROLINYL)]ACRIDAN, m.p. 107.degree.-109.degree.C. Conversion of the free base to the hydrochloride salt affords 10-[2-(5-METHYL-1-PYRROLINYL)]ACRIDAN HYDROCHLORIDE, m.p. 203.5.degree.-206.degree.C. (dec.) (corr.), by trituration with hot benzene in a 33% overall yield.
Analysis. Calcd. for C.sub.18 H.sub.18 N.sub.2.sup.. HCl (percent): C, 72.35; H, 6.41; N, 9.38; Cl, 11.86. Found (percent): C, 72.38; H, 6.46; N, 9.37; Cl, 11.67.
NMR delta (ppm)(D.sub.2 O, HDO reference): 1.26d (6.3), 2.01m, 2.93m, 3.68s, 4.14m, 7.3m.
Example 15
Reaction of acridan, 5,5-dimethyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-[2-(5,5-DIMETHYL-1-PYRROLINYL)]-ACRIDAN, m.p. 84.degree.-86.degree.C. Conversion of the free base to the hydrochloride salt affords 10-[2-(5,5-DIMETHYL-1-PYRROLINYL)]ACRIDAN HYDROCHLORIDE, m.p. 266.5.degree.-267.degree.C. (dec.) (corr.), by triturating first with acetone and then crystallizing from ethanol-ether in a 31% overall yield.
Analysis. Calcd. for C.sub.19 H.sub.20 N.sub.2.sup.. HCl (percent): C, 72.94; H, 6.77; N, 8.96; Cl, 11.33. Found (percent): C, 73.14; H, 6.64; N, 8.81; Cl, 11.31.
NMR delta (ppm)(D.sub.2 O, HDO reference): 1.39s, 2.01t (7.5), 3.07m, 3.72s, 7.4m.
Example 16
Reaction of acridan, 2-piperidone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 10-(3,4,5,6-TETRAHYDRO-2-PYRIDYL)ACRIDAN as a distillablle oil, b.p. 145.degree.-150.degree.C. at 0.15 mm Hg. Conversion of the free base to the hydrochloride salt affords 10-(3,4,5,5-TETRAHYDRO-2-PYRIDYL)ACRIDAN HYDROCHLORIDE as the hemihydrate, m.p. 190.5.degree.-192.5.degree.C. (corr.) by trituration with hot benzene in a 19% overall yield.
Analysis. Calcd. for C.sub.18 H.sub.18 N.sub.2.sup.. HCl.sup..1/2 H.sub.2 O (percent): C, 70.23; H, 6.55; N, 9.10; Cl, 11.52. Found (percent): C, 70.12; H, 6.15; N, 9.16; Cl, 11.56.
NMR delta (ppm)(D.sub.2 O, HDO reference(: 1.73m, 2.72m, 3.38m, 3.71s, 7.3m.
Example 17
Reaction of acridan, isopropylformamide and phosphorus oxychloride accoridng to the procedure of Example 1 provides the free base 10-[(ISOPROPYLIMINO)METHYL]ACRIDAN, m.p. 149.5.degree.-150.5.degree.C. (corr.), from n-hexane.
Analysis, Calcd. for C.sub.17 H.sub.18 N.sub.2 (percent): C, 81.56; H, 7.25; N, 11.19. Found (percent): C, 81.86; H, 7.23; N, 11.18.
NMR delta (ppm)(CDCl.sub.3, TMS reference): 1.23d, (6.3), 3.48s-7(6.3), 3.82s, 7.2m, 7.8m, 8.30s.
Example 18
Reaction of 9,9-dimethylacridan, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 9,9-DIMETHYL-10-(5-METHYL-1-PYRROLIN-2-YL)ACRIDAN as a distillable oil, b.p. 160.degree.-180.degree.C. at 0.15 mm Hg. in 11% yield. Conversion of the free base to the hydrochloride salt affords 9,9-DIMETHYL-10-(5-METHYL-1-PYRROLIN-2-YL)ACRIDAN HYDROCHLORIDE, m.p. 232.5.degree.-234.5.degree.C. (dec.) (corr.), by trituration with hot benzene.
Analysis. Calcd. for C.sub.20 H.sub.22 N.sub.2.sup.. HCl (percent): C, 73.49; H, 7.09; N, 8.57; Cl, 10.85. Found (percent): C, 73.39; H, 7.04; N, 8.74; Cl, 10.63.
NMR delta (ppm)(DMSO-d.sub.6, TMS reference): 1.35d (6.4), 1.59s, 1.75m, 3.32m, 4.36m, 7.6m, 10.63bs.
Example 19
Reaction of the enumerated phenoxazines and carboxamides in the presence of phosphorus oxychloride according to the procedure of Example 1 provides the following amidine products of Formula I:
a. 3-chloro-10-(5-methyl-1-pyrrolin-2-yl)phenoxazine from 3-chlorophenoxazine and 5-methyl-2-pyrrolidione;
b. 2,3-dichloro-10-(5-methyl-1-pyrrolin-2-yl)phenoxazine from 2,3dichlorophenoxazine and 5-methyl-2
-pyrrolidione;
c. 3,4-dichloro-10-(5-methyl-1-pyrrolin-2-yl)phenoxazine from 3,4-dichlorophenoxazine and 5-methyl-2-pyrrolidinone;
d. 4-methoxy-10-(1-pyrrolin-2-yl)phenoxazine from 4-methoxyphenoxazine and 2-pyrrolidinone;
e. 4-isopropoxy-10-(1-pyrrolin-2-yl)phenoxazine from 4-isopropoxyphenoxazine and 2-pyrrolidinone;
f. 2-methyl-10-(1-pyrrolin-2-yl)phenoxazine from 2-methylphenoxazine and 2-pyrrolidinone;
g. 4-methyl-10-(1-pyrrolin-2-yl)phenoxazine from 4-methylphenoxazine and 2-pyrrolidinone;
h. 4-n-butyl-10-(1-pyrrolin-2-yl)phenoxazine from 4-n-butylphenoxazine and 2-pyrrolidinone;
i. 2-bromo-10-(1-pyrrolin-2-yl)phenoxazine from 2-bromophenoxazine and 2-pyrrolidinone;
j. 10-(4-methyl-1-pyrrolin-2-yl)phenoxazine from phenoxazine and 4-methyl-2-pyrrolidinone;
k. 10-(5,5-di-n-butyl-1-pyrrolin-2-yl)phenoxazine from phenoxazine and 5,5-di-n-butyl-2-pyrrolidinone;
l. 10-[(methylimino)methyl]phenoxazine from phenoxazine and N-methylformamide;
m. 10-[(cyclopropylimino)methyl]phenoxazine from phenoxazine and N-cyclopropylformamide;
n. 10-[(cyclopentylimino)methyl]phenoxazine from phenoxazine and N-cyclopentylformamide;
o. 10-[(cyclohexylimino)methyl]phenoxazine from phenoxazine and N-cyclohexylformamide;
p. 10-[1-(1-cyclohexylimino)ethyl]phenoxazine from phenoxazine and N-cyclohexylacetamide;
q. 10-[1-(methylimino)ethyl]phenoxazine from phenoxazine and N-methylacetamide;
r. 4-chloro-10-[1-(methylimino)-2-methylpropyl]phenoxazine from 4-chlorophenoxazine and N-methyl-2-methylpropionamide;
s. 10-[1-(methylimino)-n-pentyl]phenoxazine from phenoxazine and n-methylvaleramide;
t. 10-(6-methyl-3,4,5-trihydro-2-pyridyl)phenoxazine from phenoxazine and 6-methyl-2-piperidone;
u. 10-(6,6-dimethyl-3,4,5-trihydro-2-pyridyl)phenoxazine from phenoxazine and 6,6-dimethyl-2-piperidone;
v. 10-[7-(3,4,5,6-tetrahydro-2H-azepinyl)]-2-(trifluoromethyl)-phenoxazine from 2-(trifluoromethyl)phenoxazine and 2-oxohexamethyleneimine.
Example 20
Reaction of the enumerated acridan and carboxamide in the presence of phosphorus oxychloride according to the procedure of Example 1 provides the following amidine products of Formula I:
a. 2-methoxy-10-(1-pyrrolin-2-yl)acridan from 2-methoxyacridan and 2-pyrrolidinone;
b. 4-methoxy-10-[(methylimino)methyl]acridan from 4-methoxyacridan and N-methylformamide;
c. 2-chloro-10-[1-(methylimino)ethyl]acridan from 2-chloroacridan and N-methylacetamide;
d. 4-chloro-10-[(cyclopropylimino)methyl]acridan from 4-chloroacridan and N-cyclopropylacetamide;
e. 10-[(cyclohexylimino)methyl]-2-(trifluoromethyl)acridan from 2-(trifluoromethyl)acridan and N-cyclohexylformamide;
f. 10-[(isopropylimino)methyl]-4-(trifluoromethyl)acridan from 4-(trifluoromethyl)acridan and N-isopropylformamide;
g. 2-chloro-9,9-dimethyl-10-(5,5-dimethyl-1-pyrrolin-2-yl)-acridan from 2-chloro-9,9-dimethylacridan and 5,5-dimethyl-2-pyrrolidinone;
h. 9,9-dimethyl-10-(4-methyl-1-pyrrolin-2-yl)-2-(trifluoromethyl)acridan from 9,9-dimethyl- 2(trifluoromethyl)acridan and 4-methyl-2-pyrrolidinone;
i. 9,9-dimethyl-4-methoxy-10-(3,4,5,6-tetrahydro-2-pyridyl)-acridan from 9,9-dimethyl-4-methoxyacridan and 2-piperidone;
j. 2-methyl-10-(6-methyl-3,4,5-trihydro-2-pyridyl)acridan from 2-methylacridan and 6-methyl-2-piperidone;
k. 4-methyl-10-(6,6-dimethyl-3,4,5-trihydro-2-pyridyl)acridan from 4-methylacridan and 6,6-dimethyl-2-piperidone;
l. 4-n-butyl-10-[7-(3,4,5,6-tetrahydro-2H-azepinyl)]acridan from 4-n-butylacridan and 2-oxohexamethyleneimine;
m. 9-methyl-10-(1-pyrrolin-2-yl)-2-(trifluoromethyl)acridan from 9-methyl-2-(trifluoromethyl)acridan and 2-pyrrolidinone;
n. 9-ethyl-9-methyl-10-(1-pyrrolin-2-yl)acridan from 9-ethyl-9-methylacridan and 2-pyrrolidinone;
o. 9,9-di-n-butyl-10-(1-pyrrolin-2-yl)acridan from 9,9-di-n-butylacridan and 2-pyrrolidinone.
While specific embodiments are disclosed in the foregoing specification, it will be appreciated that other modifications may be made without departing from the spirit and scope of the appended claims.
Claims
What is claimed is:
1. A compound selected from the group consisting of 10-imidoylacridans having the formula ##SPC3## and a non-toxic pharmaceutically acceptable acid addition salt thereof wherein X represents a divalent methylene radical of the formula --C(Z.sub.1 Z.sub.2)-- wherein Z.sub.1 and Z.sub.2 are independently selected from hydrogen or straight chain lower alkyl of from 1 to 4 carbon atoms inclusive; Y represents hydrogen, trifluoromethyl, halogen, dihalogen, lower alkyl of 1 to 4 carbon atoms inclusive, lower alkoxy of 1 to 4 carbon atoms inclusive; and is selected from the group consisting of ##EQU3## wherein R.sub.1 is lower alkyl of 1 to 4 carbon atoms inclusive or cycloalkyl of 3 to 6 carbon atoms inclusive; R.sub.2 is hydrogen or lower alkyl of 1 to 4 carbon atoms inclusive; R.sub.3 and R.sub.4 are independent members selected from the group consisting of hydrogen or lower alkyl of 1 to 4 carbon atoms inclusive; n is an integer of 3 to 5.
2. A compound according to claim 1 being a member selected from the group consisting of 10-[2-(1-pyrrolinyl)]acridan or a pharmaceutically acceptable acid addition salt thereof.
3. A compound according to claim 1 being a member selected from the group consisting of 10-[2-(5-methyl-1-pyrrolinyl)]acridan or a pharmaceutically acceptable acid addition salt thereof.
4. A compound according to claim 1 being a member selected from the group consisting of 10-[2-(5,5-dimethyl-1-pyrrolinyl)]acridan or a pharmaceutically acceptable acid addition salt thereof.
5. A compound according to claim 1 being a member selected from the group consisting of 10-(3,4,5,6-tetrahydro-2-pyridyl)acridan or a pharmaceutically acceptable acid addition salt thereof.
6. A compound according to claim 1 being a member selected from the group consisting of 10-[(isopropylimino)methyl]acridan or a pharmaceutically acceptable acid addition salt thereof.
7. A compound according to claim 1 being a member selected from the group consisting of 9,9-dimethyl-10-(5-methyl-1-pyrrolin-2-yl)-acridan or a pharmaceutically acceptable acid addition salt thereof.
Patent Citations (2)
| Patent | Date | Inventor | Cited By |
|---|---|---|---|
| US3498986 | 1970-03-01 | Meisels et al. | |
| US3770727 | 1973-11-01 | Brack |
Non-Patent Literature (1)
- Moskoukina et al, Chemical Abstracts, vol. 73, 14,649n (1970).