US 4,762,841 AGrant

Substituted 9-Amino-Spiro(cycloalkyl(b)quinoline-2,1'cycloalkanes)

Issue Date:1988-08-09

•51 Claims

Abstract

There are disclosed compounds having the formula ##STR1## wherein m is 1 or 2; n is 1 or 2; p is 1-5; X is hydrogen, loweralkyl, cycloalkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, formyl, loweralkylcarbonyl, arylcarbonyl, --SH, loweralkylthio, --NHCOR.sub.2 or --NR.sub.3 R.sub.4 where R.sub.2 is hydrogen or loweralkyl, and R.sub.3 and R.sub.4 are independently hydrogen, loweralkyl or cycloalkyl; R is hydrogen, loweralkyl or loweralkylcarbonyl; and R.sub.1 is hydrogen, loweralkyl, loweralkylcarbonyl, aryl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, oxygen-bridged arylloweralkyl or oxygen-bridged diarylloweralkyl; stereo, optical and geometrical isomers thereof, and pharmaceutically acceptable acid addition salts thereof, which are useful for enhancing memory.

Metadata

Assignee

Hoechst-Roussel Pharmaceuticals Inc.

Inventor

Gregory M. Shutske

Application Information

Application Number:US 0318256

Filing Date:1987-03-30

Priority Date:1987-03-30

Art Unit:129

Classifications

IPC:

C07D22120A61K 31435

Field of Search:

54651415278

Patent Drawings

This patent does not have any drawings.

Claims

I claim:

1. A compound of the formula ##STR9## wherein m is 1 or 2; n is 1 or 2; p is 1-5; X is hydrogen, lowralkyl, cycloalkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, formyl, loweralkylcarbonyl, arylcarbonyl, --SH, loweralkylthio, --NHCOR.sub.2 or --NR.sub.3 R.sub.4 where R.sub.2 is hydrogen or loweralkyl, and R.sub.3 and R.sub.4 are independently hydrogen, loweralkyl or cycloalkyl; R is hydrogen, loweralkyl, or loweralkylcarbonyl; and R.sub.1 is hydrogen, loweralkyl, loweralkylcarbonyl, aryl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, aryloxyloweralkyl or di-aryloxy-loweralkyl; a stereo, optical, or geometrical isomer thereof, or a pharmaceutically acceptable acid addition salt thereof, the term aryl in each occurrence signifying a phenyl group optionally substituted with 1, 2 or 3 substituents each of which being independently loweralkyl, loweralkoxy, halogen, hydroxy, trifluoromethyl, phenoxy or benzyloxy, and the term cycloalkyl in each occurrence signifying a cycloalkyl of 3 to 7 carbon atoms.

2. The compound as defined in claim 1, where m is 1, n is 2 and p is 3.

3. The compound as defined in claim 2, where R is hydrogen and R.sub.1 is hydrogen or arylloweralkyl.

4. The compound as defined in claim 3, where X is hydrogen, loweralkyl or trifluoromethyl.

5. The compound as defined in claim 1, which is 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopropane].

6. The compound as defined in claim 1, which is 9-amino-6-chloro-3,4-dihydrospiro[acridine-2(1H),1'-cyclopane].

7. The compound as defined in claim 1, which is 9-benzylamino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopropane].

8. The compound as defined in claim 1, which is 1,2-dihydro-9-methylaminospiro[acridine-3(4H),1'-cyclopropane].

9. The compound as defined in claim 1, which is 9-anilino-1,2-dihydrospiro[acridine-3(4H),1'-cyclopropane].

10. The compound as defined in claim 1, which is 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

11. The compound as defined in claim 1, which is 9-amino-3,4-dihydro-7-methylspiro[acridine-2(1H),1'-cyclobutane].

12. The compound as defined in claim 1, which is 3,4-dihydro-9-propylaminospiro[acridine-2(1H),1'-cyclobutane].

13. The compound as defined in claim 1, which is 9-(4-chlorobenzylamino)-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

14. The compound as defined in claim 1, which is 9-anilino-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

15. The compound as defined in claim 1, which is 9-amino-1,2-dihydro-6-fluorospiro[acridine-3(4H),1'-cyclobutane].

16. The compound as defined in claim 1, which is 9-benzylamino-1,2-dihydrospiro[acridine-2(1H),1'-cyclobutane].

17. The compound as defined in claim 1, which is 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopentane].

18. The compound as defined in claim 1, which is 3,4-dihydro-9-ethylaminospiro[acridine-2(1H),1'-cyclopentane].

19. The compound as defined in claim 1, which is 3,4-dihydro-9-(4-fluorobenzylamino)spiro[acridine-2(1H),1'-cyclopentane].

20. The compound as defined in claim 1, which is 9-amino-1,2-dihydro-7-methoxyspiro[acridine-3(4H),1'-cyclopentane].

21. The compound as defined in claim 1, which is 1,2-dihydro-9-methylaminospiro[acridine-3(4H),1'-cyclopentane].

22. The compound as defined in claim 1, which is 9-anilino-1,2-dihydrospiro[acridine-3(4H),1'-cyclopentane].

23. The compound as defined in claim 1, which is 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclohexane].

24. The compound as defined in claim 1, which is 3,4-dihydro-9-propylaminospiro[acridine-2(1H),1'-cyclohexane].

25. The compound as defined in claim 1, which is 3,4-dihydro-9-(4-methylbenzylamino)spiro[acridine-2(1H),1'-cyclohexane].

26. The compound as defined in claim 1, which is 9-(4-chloroanilino)-3,4-dihydrospiro[acridine-2(1H),1'-cyclohexane].

27. The compound as defined in claim 1, which is 9-amino-1,2-dihydro-6-trifluoromethylspiro[acridine-3(4H),1'-cyclohexane].

28. The compound as defined in claim 1, which is 9-benzylamino-1,2-dihydrospiro[acridine-3(4H),1'-cyclohexane].

29. The compound as defined in claim 1, which is 9-amino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclopentane].

30. The compound as defined in claim 1, which is 9-amino-6-chloro-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclopentane ].

31. The compound as defined in claim 1, which is 1,2-dihydro-9-propylaminospiro[cyclopenta[b]quinoline-2,1'-cyclopentane].

32. The compound as defined in claim 1, which is 9-anilino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclopentane].

33. The compound as defined in claim 1, which is 9-amino-1,3-dihydro-7-methoxyspiro[cyclopenta[b]quinoline-2,1'-cyclohexane ].

34. The compound as defined in claim 1, which is 9-benzylamino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclohexane].

35. The compound as defined in claim 1, which is 11-amino-6,7,8,10-tetrahydrospiro[cyclohepta[b]quinoline-9,1'-cyclohexane] .

36. The compound as defined in claim 1, which is 11-amino-6,7,9,10-tetrahydrospiro[cyclohepta[b]quinoline-8,1'-cyclohexane] .

37. The compound as defined in claim 1, which is 11-amino-6,8,9,10-tetrahydrospiro[cyclohepta[b]quinoline-7,1'-cyclohexane] .

38. A pharmaceutical composition for increasing the cholinergic function in a mammal which comprises an effective amount of a compound as defined in claim 1 and a carrier therefor.

39. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopropane].

40. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

41. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

42. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclohexane].

43. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclopentane].

44. The pharmaceutical composition as defined in claim 38 which comprises 9-amino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclohexane].

45. A method of increasing the cholinergic function in a mammal which comprises administering to the mammal an effective cholinergic function increasing amount of a compound as defined in claim 1.

46. The method as defined in claim 45, which comprises the administration of 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopropane].

47. The method as defined in claim 45, which comprises the administration of 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclobutane].

48. The method as defined in claim 45, which comprises the administration of 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclopentane].

49. The method as defined in claim 45, which comprises the administration of 9-amino-3,4-dihydrospiro[acridine-2(1H),1'-cyclohexane].

50. The method as defined in claim 45, which comprises the administration of 9-amino-1,3-dihydrosphiro[cyclopenta[b]quinoline-2,1'-cyclopentane].

51. The method as defined in claim 45, which comprises the administration of 9-amino-1,3-dihydrospiro[cyclopenta[b]quinoline-2,1'-cyclophexane].

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Abstract

Claims