USRE49825EActiveUtility
Piperidinyl nociceptin receptor compounds
Est. expiryDec 2, 2035(~9.4 yrs left)· nominal 20-yr term from priority
C07D 401/04C07D 401/14C07D 405/14C07D 471/04C07D 471/10
74
PatentIndex Score
0
Cited by
169
References
20
Claims
Abstract
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.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A compound of structural formula (I):
or salts, hydrates or solvates thereof wherein:
B is hydrogen;
R 1 and R 2 together with the carbon atoms to which they are attached form aryl, substituted aryl, heteroaryl or substituted heteroaryl;
X is hydrogen, —CH═NOR 4 , —C(O)NR 5 R 6 , alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl;
Y is hydrogen, —CH═NOR 7 , —C(O)NR 8 R 9 , alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl;
R 4 is hydrogen, alkyl or substituted alkyl;
R 5 is hydrogen, alkyl or substituted alkyl;
R 6 is hydrogen, alkyl, substituted alkyl or —OR 15 ;
R 7 is hydrogen, alkyl or substituted alkyl;
R 8 and R 9 are independently hydrogen, alkyl or substituted alkyl; and
L is C 4 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl, C 8 cycloalkyl, (C 3 -C 8 ) substituted cycloalkyl, cyclohexyl substituted with
(C 3 -C 8 ) cycloheteroalkyl, C 3 substituted cycloheteroalkyl, C 5 substituted cycloheteroalkyl, C 6 substituted cycloheteroalkyl, C 7 substituted cycloheteroalkyl, C 8 substituted cycloheteroalkyl,
2. The compound of claim 1 , wherein R 1 and R 2 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 C 4 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl or C 8 cycloalkyl.
4. The compound of claim 1 , wherein L is
or
n is 0, 1 or 2, K is —NR 31 — or —O— and R 31 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, or 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—, R 32 is alkyl, halo, —OR 33 , —NHR 34 , —CF 3 or —CN; n is an integer between 0 and 4; R 33 is hydrogen, alkyl, —(CO)NR 35 R 36 or —SO 2 NR 37 R 38 ; and R 34 , R 35 , R 36 , R 37 and R 38 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 1or 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 1or the pharmaceutical composition of claim 15 .
20. The compound of claim 1 selected from the group consisting of:Cited by (0)
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