The present invention provides novel piperidinyl-containing nociceptin receptor ligand compounds and pharmaceutical compositions useful in the treatment of neurological diseases and conditions where such ligands mediate the negative effects of the condition. Such neurological diseases and conditions
The present invention provides novel piperidinyl-containing nociceptin receptor ligand compounds and pharmaceutical compositions useful in the treatment of neurological diseases and conditions where such ligands mediate the negative effects of the condition. Such neurological diseases and conditions include acute and chronic pain, substance abuse/dependence, alcohol addiction, anxiety, depression, sleep disorders, gastrointestinal disorders, renal disorders, cardiovascular disorders and Parkinson's disease.
대표청구항▼
1. A compound of structural formula (I): or salts, hydrates or solvates thereof wherein: B is hydrogen;R1 and R2 together with the carbon atoms to which they are attached form aryl, substituted aryl, heteroaryl or substituted heteroaryl;X is hydrogen, —CH═NOR4, —C(O)NR5R6, alkyl, substituted alkyl,
1. A compound of structural formula (I): or salts, hydrates or solvates thereof wherein: B is hydrogen;R1 and R2 together with the carbon atoms to which they are attached form aryl, substituted aryl, heteroaryl or substituted heteroaryl;X is hydrogen, —CH═NOR4, —C(O)NR5R6, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl;Y is hydrogen, —CH═NOR7, —C(O)NR8R9, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl;R4 is hydrogen, alkyl or substituted alkyl;R5 is hydrogen, alkyl or substituted alkyl;R6 is hydrogen, alkyl, substituted alkyl or —OR15;R7 is hydrogen, alkyl or substituted alkyl;R8 and R9 are independently hydrogen, alkyl or substituted alkyl;L is C4 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, (C3-C8) substituted cycloalkyl, cyclohexyl substituted with (C3-C8 cycloheteroalkyl, C3 substituted cycloheteroalkyl, C5 substituted cycloheteroalkyl, C6 substituted cycloheteroalkyl, C7 substituted cycloheteroalkyl, C8 substituted cycloheteroalkyl, 2. The compound of claim 1, wherein R1 and R2 together with the carbon atoms to which they are attached form phenyl, substituted phenyl, pyridyl or substituted pyridyl. 3. The compound of claim 1, wherein L is C4 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl or C8 cycloalkyl. 4. The compound of claim 1, wherein L is or n is 0, 1 or 2, K is —NR31— or —O— and R31 is hydrogen, alkyl or substituted alkyl. 5. The compound of claim 1, wherein L is a substituted cyclohexyl group or cyclohexyl substituted with 6. The compound of claim 5, wherein L is wherein Z is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; and U is hydrogen, alkyl or absent. 7. The compound of claim 6, wherein Z is alkyl, substituted alkyl, heteroalkyl or substituted heteroalkyl. 8. The compound of claim 7, wherein Z is and U is hydrogen. 9. The compound of claim 5, wherein L is cyclohexyl substituted with 10. The compound of claim 1 of structural formula (II): wherein D is —CH— or —N—, R32 is alkyl, halo, —OR33, —NHR34, —CF3 or —CN; n is an integer between 0 and 4; R33 is hydrogen, alkyl, —(CO)NR35R36 or —SO2NR37R38; and R34, R35, R36, R37 and R38 are independently hydrogen or alkyl. 11. The compound of claim 1, having the structure: 12. The compound of claim 1, having the structure: 13. The compound of claim 1, having the structure: 14. The compound of claim 1 selected from the group consisting of: 15. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable vehicle. 16. A method of treating a nociceptin receptor mediated disorder in a patient comprising administering to the patient in need thereof a compound of claim 1 or the pharmaceutical composition of claim 15. 17. A method of modulating a nociceptin receptor comprising administering a compound of claim 15 or the pharmaceutical composition of claim 15. 18. A method of treating or preventing substance abuse and dependence in a patient comprising administering to the patient in need thereof a compound of claim 1 or the pharmaceutical composition of claim 15. 19. A method of modulating a nociceptin receptor to treat or prevent substance abuse and dependence in a patient comprising administering to the patient in need thereof a compound of claim 11 or the pharmaceutical composition of claim 15.
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