Treatment of substance abuse

• US 20070167438A1
• Filed: 01/12/2007
• Published: 07/19/2007
• Est. Priority Date: 01/13/2006
• Status: Abandoned Application

• Current Assignee: Wyeth LLC (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Rosenzweig-Lipson, Sharon
• Application Number:
  US11/653,027
• Publication Number:
  US 20070167438A1
• Time in Patent Office: Days
• US Class Current: 514/220
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

The present invention provides methods and compositions for use in the treatment, prevention, and/or alleviation of drug abuse and/or its symptoms. In particular, the invention demonstrates that compositions comprising compounds of formula I are useful in such treatment, prevention, and/or alleviation:
or a pharmaceutically acceptable salt thereof, wherein each of n, R¹, R², R³, R⁴, R⁵, and R⁶ are as defined herein.

Claims

1. A method for treating a patient suffering from, or susceptible to, one or more symptoms of substance abuse, dependence, or withdrawal comprising administering to said patient a compound of formula I:

2. The method according to claim 1, wherein R¹ and R² are each independently R, OR, halogen, cyano, or —

C_1-3 perfluoroalkyl.

3. The method according to claim 2, wherein R¹ and R² are each independently hydrogen, halogen, cyano, —

OR wherein R is hydrogen, C_1-3 alkyl, or trifluoromethyl.

4. The method according to claim 3, wherein each of R¹ and R² is hydrogen.

5. The method according to claim 1, wherein R³ and R⁴ are taken together to form a saturated or unsaturated 5-8 membered carbocyclic ring, wherein said ring is optionally substituted with 1-3 groups independently selected from halogen, —

R, or OR.

6. The method according to claim 5, wherein R³ and R⁴ are taken together to form a saturated or unsaturated 5-6 membered carbocyclic ring, wherein said ring is optionally substituted with 1-3 groups independently selected from halogen, —

R, or OR.

7. The method according to claim 6, wherein said compound is of formula II:

8. The method according to claim 1, wherein said compound is of formula I-a or I-b:

9. The method according to claim 1, wherein said compound is of formula I-c or I-d:

10. The method according to claim 1, wherein said compound is of formula III:

11. The method according to claim 1, wherein said compound is selected from:

4,5,6,7,9a,10,11,12,13,13a-decahydro-9H-[1,4]diazepino[6,7,1-de]phenanthridine;

2-bromo-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

2-bromo-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

2-chloro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

2-chloro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline hydrochloride;

2-phenyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

1-fluoro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

1-fluoro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

1-(trifluoromethyl)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

4,5,6,7,9,9a10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

(9aR,12aS)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

(9aS,12aR)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline;

(9aR,14aS)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

or

(9aS,14aR)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino[6,7,1-ij]quinoline;

or a pharmaceutically acceptable salt thereof.

12. A method for treating a patient suffering from, or susceptible to, one or more symptoms of substance abuse, dependence, or withdrawal comprising administering to the patient a composition comprising a compound according to claim 1, and one or more pharmaceutically acceptable carriers.

13. The method according to claim 12, wherein said substance is a recreational substance, a pharmacologic agent, or an illicit drug.

14. The method according to claim 13, wherein said substance is a pain reliever, a tranquilizer, a stimulant, a tobacco product, or a sedative.

15. The method according to claim 13, wherein said substance is Vicodin®

, Lortab®

, Lorcet®

, Percocet®

, Percodan®

, Tylox®

, Hydrocodone, OxyContin®

, methadone, Tramadol, marijuana, heroine, cocaine, ecstasy, LSD, PCP, or methamphetamine.