Claims
- 1. A compound of formula I:
- 2. The compound of claim 1, wherein the mono- or bicyclic, carbo- or heterocyclic ring is selected from the group consisting of naphthyl, indolyl, furyl, thiazolyl, thienyl, pyridyl, and phenyl.
- 3. The compound of claim 1, wherein the compound has an affinity for FKBP-type immunophilins.
- 4. The compound of claim 3, wherein the FKBP-type immunophilins are FKBP12.
- 5. The compound of claim 1, wherein the compound inhibits rotamase enzyme activity.
- 6. The compound of claim 1, wherein the compound is selected from the group consisting of:
3-Phenylpropyl (2S)-1-(-cyclohexylcarbamoyl)-2-pyrrolidinecarbothiate (17); Phenethyl (2S)-N-(cyclohexylcarbamoyl)-2-pyrrolidinecarbothiate (18); 3-(2,3,5-Trimethylphenyl)propyl 1-(1-adamantylcarbamoyl)-2-pyrrolidinecarbothioate (19); 3-(2,3,5-Trimethylphenyl)propyl 1-(cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (20); 3-(3-Fluorophenyl)propyl (2S)-1-(Cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (21); 3-(2-Fluorophenyl)propyl (2S)-1-(1-adamantylcarbamoyl)-2-pyrrolidinecarbothioate (22); 3-(2-Fluorophenyl)propyl (2S)-1-(cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (23); 3-(4-Methylphenyl)propyl (2S)-1-(cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (24); 3-(4-Methylphenyl)propyl (2S)-1-(1-adamantylcarbamoyl)-2-pyrrolidinecarbothioate (25); 3-(4-Methylphenyl)propyl (2S)-1-(tert-butylcarbamoyl)-2-pyrrolidinecarbothioate (26); 3-(2-Chlorophenyl)propyl (2S)-1-cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (27); 3-(3,5-Dimethoxyphenyl)propyl (2S)-1-{[(1S)-1-(1-naphthyl)ethyl]-carbamoyl}-2-pyrrolidinecarbothioate (28); 3,3-Diphenylpropyl (2S)-1-[(1,1,3,3-tetramethylbutyl)carbamoyl]-2-pyrrolidinecarbothioate (29); 3-Cyclohexylpropyl (2S)-1-[(2,6-diisopropylphenyl)carbamoyl]-2-pyrrolidinecarbothioate (31); 3-Cyclohexylpropyl (2S)-1-(hexylcarbamoyl)-2-pyrrolidinecarbothioate (32); 3,3-Diphenylpropyl (2S)-1-[(2,4-dimethoxyphenyl)carbamoyl]-2-pyrrolidinecarbothioate (33); 3-(3,5-Dimethoxyphenyl)propyl (2S)-1-{[(1S,2R)-2-phenyl-cyclopropyl]carbamoyl]-2-pyrrolidinecarbothioate (34); 3-Phenylpropyl (2S)-1-[(2,4-Dimethoxyphenyl)carbamoyl]-2-pyrrolidinecarbothioate (35); 3-Phenylpropyl (2S)-1-(1-adamantylcarbamoyl)-2-pyrrolidinecarbothioate (36); 3-Phenylpropyl (2S)-1-(1-cyclohexylcarbamoyl)-2-pyrrolidinecarbothioate (37); 3-Phenylpropyl (2S)-1-[1-adamantylamino) (thioxo)-methyl]-2-pyrrolidinecarbothioate (38); 3-(3,4,5-Trimethoxyphenyl)propyl (2S)-1-(hexylcarbamoyl)-2-pyrrolidinecarbothioate (39); 3-(3,4,5-Trimethoxyphenyl)propyl (2S)-1-(benzylcarbamoyl)-2-pyrrolidinecarbothioate (40); 3-Phenylpropyl (2S)-1-(dimethylcarbamoyl)-2-pyrrolidinecarbothioate (41); 3-Phenylpropyl (2S)-1-(1-pyrrolidinylcarbonyl)-2-pyrrolidinecarbothioate (42); 3-Phenylpropyl (2S)-1-(morphilinocarbonyl)-2-pyrrolidinecarbothioate (43); 3-Phenylpropyl (2S)-1-(diisopropylcarbamoyl)-2-pyrrolidinecarbothioate (44); 3-Phenylpropyl (2S)-1-[methyl(phenyl)carbamoyl]-2-pyrrolidinecarbothioate (45); and 3-Phenylpropyl (2S)-1-(diphenylcarbamoyl)-2-pyrrolidinecarbothioate (46).
- 7. A pharmaceutical composition comprising a neurotrophically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
- 8. A method of effecting a neuronal activity in an animal, comprising:
administering to the animal a neurotrophically effective amount of the compound of claim 1.
- 9. The method of claim 8, wherein the neuronal activity is selected from the group consisting of stimulation of damaged neurons, promotion of neuronal regeneration, prevention of neurodegeneration and treatment of neurological disorder.
- 10. The method of claim 9, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, physical damage to the brain, physical damage to the spinal cord, stroke associated with brain damage, and neurological disorder relating to neurodegeneration.
- 11. The method of claim 10, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, and amyotrophic lateral sclerosis.
- 12. A compound of formula II:
- 13. The compound of claim 12, wherein Ar is selected from the group consisting of naphthyl, indolyl, furyl, thiazolyl, thienyl, pyridyl, and phenyl.
- 14. The compound of claim 12, wherein the compound has an affinity for FKBP-type immunophilins.
- 15. The compound of claim 14, wherein the FKBP-type immunophilins are FKBP12.
- 16. The compound of claim 12, wherein the compound inhibits rotamase enzyme activity.
- 17. A pharmaceutical composition comprising a neurotrophically effective amount of the compound of claim 12 and a pharmaceutically acceptable carrier.
- 18. A method of effecting a neuronal activity in an animal, comprising:
administering to the animal a neurotrophically effective amount of the compound of claim 12.
- 19. The method of claim 18, wherein the neuronal activity is selected from the group consisting of stimulation of damaged neurons, promotion of neuronal regeneration, prevention of neurodegeneration and treatment of neurological disorder.
- 20. The method of claim 19, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, physical damage to the brain, physical damage to the spinal cord, stroke associated with brain damage, and neurological disorder relating to neurodegeneration.
- 21. The method of claim 20, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, and amyotrophic lateral sclerosis.
- 22. A compound of formula III:
- 23. The compound of claim 22, wherein Ar is selected from the group consisting of naphthyl, indolyl, furyl, thiazolyl, thienyl, pyridyl, and phenyl.
- 24. The compound of claim 22, wherein the compound has an affinity for FKBP-type immunophilins.
- 25. The compound of claim 24, wherein the FKBP-type immunophilins are FKBP12.
- 26. The compound of claim 22, wherein the compound inhibits rotamase enzyme activity.
- 27. A pharmaceutical composition comprising a neurotrophically effective amount of the compound of claim 22 and a pharmaceutically acceptable carrier.
- 28. A method of effecting a neuronal activity in an animal, comprising:
administering to the animal a neurotrophically effective amount of the compound of claim 22.
- 29. The method of claim 28, wherein the neuronal activity is selected from the group consisting of stimulation of damaged neurons, promotion of neuronal regeneration, prevention of neurodegeneration and treatment of neurological disorder.
- 30. The method of claim 29, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, physical damage to the brain, physical damage to the spinal cord, stroke associated with brain damage, and neurological disorder relating to neurodegeneration.
- 31. The method of claim 30, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, and amyotrophic lateral sclerosis.
- 32. A compound of formula IV:
- 33. The compound of claim 32, wherein Ar is selected from the group consisting of naphthyl, indolyl, furyl, thiazolyl, thienyl, pyridyl, and phenyl.
- 34. The compound of claim 32, wherein the compound has an affinity for FKBP-type immunophilins.
- 35. The compound of claim 34, wherein the FKBP-type immunophilins are FKBP12.
- 36. The compound of claim 32, wherein the compound inhibits rotamase enzyme activity.
- 37. A pharmaceutical composition comprising a neurotrophically effective amount of the compound of claim 32 and a pharmaceutically acceptable carrier.
- 38. A method of effecting a neuronal activity in an animal, comprising:
administering to the animal a neurotrophically effective amount of the compound of claim 32.
- 39. The method of claim 38, wherein the neuronal activity is selected from the group consisting of stimulation of damaged neurons, promotion of neuronal regeneration, prevention of neurodegeneration and treatment of neurological disorder.
- 40. The method of claim 39, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, physical damage to the brain, physical damage to the spinal cord, stroke associated with brain damage, and neurological disorder relating to neurodegeneration.
- 41. The method of claim 40, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, and amyotrophic lateral sclerosis.
Parent Case Info
[0001] This application is a continuation-in-part application of U.S. patent application Serial No. 08/775,585 filed Dec. 31, 1996.
Divisions (2)
|
Number |
Date |
Country |
Parent |
09393650 |
Sep 1999 |
US |
Child |
09885178 |
Jun 2001 |
US |
Parent |
08997451 |
Dec 1997 |
US |
Child |
09393650 |
Sep 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08775585 |
Dec 1996 |
US |
Child |
08997451 |
Dec 1997 |
US |