Claims
- 1. A compound of formula I
- 2. The compound of claim 1, wherein the compound is non-immunosuppressive.
- 3. The compound of claim 1, wherein said compound is selected from the group consisting of:
3,3-dimethyl-N-[2-(5-phenylpentanoyl)-tetrahydro-1H-1-pyrazolyl]-1,2-pentanedione; 3,3-dimethyl-[2-(3-phenylpropanoyl)tetrahydro-1H-1-pyrazolyl]-1,2-pentanedione; 3,3-dimethyl-1-[2-(5-(3-pyridyl)pent-4-ynoyl)-pyrazolidinyl]pentane-1,2-dione; 3,3-dimethyl-1-[2-(5-(cyano)pent-4-ynoyl)pyrazolidinyl]-pentane-1,2-dione; 3,3-dimethyl-1-[2-(4-phenylbutanoyl)pyrazolidinyl]-pentane-1,2-dione; 3,3-dimethyl-1-[2-(6-phenylhexanoyl)pyrazolidinyl]-pentane-1,2-dione; 3,3-dimethyl-1-[2-(5-(3-pyridyl)pentanoyl)-pyrazolidinyl]pentane-1,2-dione; 3-phenylpropyl 2-(3,3-dimethyl-2-oxopentanoyl)-pyrazolidinecarboxylate; 3-(3-pyridyl)propyl 2-(3,3-dimethyl-2-oxopentanoyl)pyrazolidinecarboxylate; 4-phenylbutyl 2-(3,3-dimethyl-2-oxopentanoyl)-pyrazolidinecarboxylate; 2-phenylethyl 2-(3,3-dimethyl-2-oxopentanoyl)-pyrazolidinecarboxylate; 3,3-dimethyl-1-[2-(6-phenylhexanoyl)perhydro-pyridazinyl]pentane-1,2-dione; 3,3-dimethyl-1-[2-(6-(3-pyridyl)hexanoyl)-perhydropyridazinyl]pentane-1,2-dione; 3-phenylpropyl 2-(3,3-dimethyl-2-oxopentanoyl)-perhydropyridazinecarboxylate; 4-phenylbutyl 2-(3,3 - dimethyl-2-oxopentanoyl)perhydropyridazinecarboxylate; 5-phenylpentyl 2-(3,3-dimethyl-2-oxopentanoyl)-perhydropyridazinecarboxylate; 4-(3-pyridyl)butyl 2-(3,3-dimethy-2-oxopentanoyl)-perhydropyridazinecarboxylate; 3,3-dimethyl-1-[2-({5-phenyl}pentanoyl)perhydropyridazinyl]pentane-1,2-dione; and pharmaceutically acceptable salts, esters and solvates thereof.
- 4. A pharmaceutical composition comprising:
(i) a therapeutically effective amount of a compound of formula I: 62or a pharmaceutically acceptable salt, ester or solvate thereof, wherein: n is 1-3; R1 is selected from the group consisting of —CR3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3,—PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N(R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, —CONR3CN, 63wherein said R1 group is either unsubstituted or additionally substituted with R3; R2 is selected from the group consisting of hydrogen, C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, aryl, heteroaryl, carbocycle, or heterocycle, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocycle, or heterocycle is unsubstituted on substituted with one or more substituents selected from R3; R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, carbonyl, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, or heterocycle group; and X is O or S; and (ii) a pharmaceutically acceptable carrier.
- 5. The pharmaceutical composition of claim 4, further comprising an additional neurotrophic factor.
- 6. The pharmaceutical composition of claim 5, wherein the additional neurotrophic factor is selected from the group consisting of neurotrophic growth factor, brain derived growth factor, glial derived growth factor, cilial neutrophic factor, insulin growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, platelet-derived growth factor, neurotropin-3, neurotropin-4 and neurotropin-5.
- 7. A method for effecting a neuronal activity in a mammal, comprising administering to the mammal an effective amount of a compound of formula I:
- 8. The method of claim 7, 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 a neurological disorder.
- 9. The method of claim 8, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, traumatic injury to the brain, physical damage to the spinal cord, stroke associated with brain damage, and a neurological disorder relating to neurodegeneration.
- 10. The method of claim 11, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
- 11. A compound of formula II:
- 12. The compound of claim 11, wherein the compound is non-immunosuppressive.
- 13. The compound of claim 11, which is selected from the group consisting of:
3-phenylpropyl 2-[benzylsulfonyl]pyrazolidine-carboxylate; 4-phenylbutyl 2-[benzylsulfonyl]perhydropyridazine-carboxylate; 1-(5-phenylpentanoyl)-2-(benzylsulfonyl)tetrahydro-1H-1-pyrazole; and pharmaceutically acceptable salts, esters and solvates thereof.
- 14. A pharmaceutical composition comprising:
(i) a therapeutically effective amount of a compound of formula II: 68or a pharmaceutically acceptable salt, ester or solvate thereof, wherein:
n is 1-3; R1 is selected from the group consisting of —CR3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3, —PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N(R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, —CONR3CN, 69wherein said R1 group is either unsubstituted or additionally substituted with R3; R2 is selected from the group consisting of hydrogen, C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, aryl, heteroaryl, carbocycle, or heterocycle, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocycle, or heterocycle is unsubstituted or substituted with one or more substituents selected from R3; and R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, carbonyl, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, or heterocycle group; and (ii) a pharmaceutically acceptable carrier.
- 15. The pharmaceutical composition of claim 14, further comprising an additional neurotrophic factor.
- 16. The pharmaceutical composition of claim 15, wherein the additional neurotrophic factor is selected from the group consisting of neurotrophic growth factor, brain derived growth factor, glial derived growth factor, cilial neutrophic factor, insulin growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, platelet-derived growth factor, neurotropin-3, neurotropin-4 and neurotropin-5.
- 17. A method for effecting a neuronal activity in a mammal, comprising administering to the mammal an effective amount of a compound of formula II:
- 18. The method of claim 17, 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 a neurological disorder.
- 19. The method of claim 18, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, traumatic injury to the brain, physical damage to the spinal cord, stroke associated with brain damage, and a neurological disorder relating to neurodegeneration.
- 20. The method of claim 19, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
- 21. A compound of formula III:
- 22. The compound of claim 21, wherein the compound is non-immunosuppressive.
- 23. The compound of claim 21, wherein said compound is 1-(S-phenylpentanoyl)-2-(N,N-dicyclohexylcarbamoyl)-tetrahydro-1H-1-pyrazole or a pharmaceutically acceptable salt, ester or solvate thereof.
- 24. A pharmaceutical composition comprising:
(i) a therapeutically effective amount of a compound of formula III: 74or a pharmaceutically acceptable salt, ester or solvate thereof, wherein: n is 1-3; R1 is selected from the group consisting of —CR3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3,—PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N (R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, —CONR3CN, 75wherein said R1 group is either unsubstituted or additionally substituted with R3; R and R2 are independently C1-C9 alkyl, C2-C9 alkenyl, aryl, heteroaryl, carbocycle, or heterocycle, wherein said alkyl, alkenyl, aryl, heteroaryl, carbocycle, or heterocycle is unsubstituted or substituted with one or more substituent(s) selected from R3; and R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, carbonyl, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, or heterocycle group; and (ii) a pharmaceutically acceptable carrier.
- 25. The pharmaceutical composition of claim 24, further comprising an additional neurotrophic factor.
- 26. The pharmaceutical composition of claim 25, wherein the additional neurotrophic factor is selected from the group consisting of neurotrophic growth factor, brain derived growth factor, glial derived growth factor, cilial neutrophic factor, insulin growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, platelet-derived growth factor, neurotropin-3, neurotropin-4 and neurotropin-5.
- 27. A method for effecting a neuronal activity in a mammal, comprising administering to the mammal an effective amount of a compound of formula III:
- 28. The method of claim 27, 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 a neurological disorder.
- 29. The method of claim 28, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, traumatic injury to the brain, physical damage to the spinal cord, stroke associated with brain damage, and a neurological disorder relating to neurodegeneration.
- 30. The method of claim 29, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
- 31. A compound of formula IV:
- 32. The compound of claim 31, wherein the compound is non-immunosuppressive.
- 33. The compound of claim 31, wherein said compound is selected from the group consisting of:
3-phenylpropyl 2-(N-cyclohexylcarbamoyl)pyrazolidine-carboxylate; 4-phenylbutyl 2-(N-cyclohexylcarbamoyl)perhydro-pyridazinecarboxylate; 1-(5-phenylpentanoyl)-2-(N-cyclohexylcarbamoyl)-tetrahydro-1H-1-pyrazole; and pharmaceutically acceptable salts, esters and solvates thereof.
- 34. A pharmaceutical composition comprising:
(i) a therapeutically effective amount of a compound of formula IV: 80or a pharmaceutically acceptable salt, ester or solvate thereof, wherein:
n is 1-3; R1 is selected from the group consisting of —CR3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3,—PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N(R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, —CONR3CN, 81wherein said R1 group is either unsubstituted or additionally substituted with R3; and R2 is C1-C9 alkyl, C2-C9 alkenyl, aryl, heteroaryl, carbocycle, or heterocycle, wherein said alkyl, alkenyl, aryl, heteroaryl, carbocycle, or heterocycle is substituted with one or more substituent(s) selected from R3; and R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, carbonyl, cyano, nitro, imino, sulfonyl, thiocarbonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, or heterocycle group; and (ii) a pharmaceutically acceptable carrier.
- 35. The pharmaceutical composition of claim 34, further comprising an additional neurotrophic factor.
- 36. The pharmaceutical composition of claim 35, wherein the additional neurotrophic factor is selected from the group consisting of neurotrophic growth factor, brain derived growth factor, glial derived growth factor, cilial neutrophic factor, insulin growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, platelet-derived growth factor, neurotropin-3, neurotropin-4 and neurotropin-5.
- 37. A method for effecting a neuronal activity in a mammal, comprising administering to the mammal an effective amount of a compound of formula IV:
- 38. The method of claim 37, 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 a neurological disorder.
- 39. The method of claim 38, wherein the neurological disorder is selected from the group consisting of peripheral neuropathy caused by physical injury or disease state, traumatic injury to the brain, physical damage to the spinal cord, stroke associated with brain damage, and a neurological disorder relating to neurodegeneration.
- 40. The method of claim 39, wherein the neurological disorder relating to neurodegeneration is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
- 41. A process for preparing a compound having the formula (I):
- 42. A process for preparing a compound having the formula (II):
- 43. A process for preparing a compound having the formula (IV):
Parent Case Info
[0001] This application is a Continuation-in-Part of U.S. patent application Ser. No. 09/551,618, filed Apr. 17, 2000, which claims the benefit of U.S. Provisional Application No. 60/164,950 filed Nov. 12, 1999.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60164950 |
Nov 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09551618 |
Apr 2000 |
US |
Child |
09835523 |
Apr 2001 |
US |