Human N-type calcium channel blockers

• US 20040204404A1
• Filed: 09/29/2003
• Published: 10/14/2004
• Est. Priority Date: 09/30/2002
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Zelle, Robert, Chaturvedi, Pravin
• Application Number:
  US10/674,803
• Publication Number:
  US 20040204404A1
• Time in Patent Office: Days
• US Class Current: 514/225.8
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

This invention features a method for modulating human N-type calcium channel α_1B+SFVG subunit activity. The method includes administering to a subject in need thereof an effective amount of a compound of formula (I), (II), or (III):

Claims

1. A method for modulating human N-type calcium channel α

_1B+SFVG subunit activity, comprising administering to a subject in need thereof an effective amount of a compound of formula (I), (II), or (III);

8. The method of claim 7 wherein the compound has formula (VII):

9. The method of claim 8 wherein Y is CH═

CHΦ

.

10. The method of claim 8 wherein Y is Cy.

11. The method of claim 8 wherein Y is Φ

₂CH.

12. The method of claim 8 wherein n is 0 or 1 and Y is Φ

.

20. A method of making a human N-type calcium channel α

_1B+SFVG modulating compound, the method comprising synthesizing a compound of formula (I), (II), or (III) in claim 1 and contacting the compound with a human N-type calcium channel α

_1B+SFVG subtype.

21. The method of claim 20, further comprising measuring the modulation of calcium channel activity.

22. The method of claim 21, wherein the contacting is conducted in vitro.

23. A storage medium comprising chemical structure information of a compound of formula (I), (II), or (III) in claim 1 and calcium channel actvity of a human N-type calcium channel α

_1B+SFVG when in contact with the compound.

24. A method of evaluating information comprising integrating the storage medium the storage medium of claim 23 with a computer system for evaluation or drug discovery or design.

2. A method for modulating human N-type calcium channel α

_1B+SFVG subunit activity, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (IV) or (V) or a pharmaceutically acceptable salt thereof;

3. The method of claim 2, wherein Ar represents one or two unsubstituted phenyl moieties.

4. The method of claim 2 wherein n² is 1 and X² represents a linker which spaces Ar from Z at a distance of about 3-20 Å

.

5. The method of claim 2 wherein Cy represents one or two unsubstituted cyclohexyl moieties or an unsubstituted cyclohexyl moiety and an unsubstituted phenyl moiety.

6. The method of claim 2 wherein X¹ represents a linker which spaces the Y^a and Y^b from N at a distance of about 3-20 Å

.

7. A method for modulating human N-type calcium channel α

_1B+SFVG subunit activity, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (VI) or a pharmaceutically acceptable salt thereof;

13. The method of claim 7, wherein the compound is:

14. The method of claim 7, wherein the compound is:

15. A method for modulating human N-type calcium channel α

_1B+SFVG subunit activity, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (VIII) or a pharmaceutically acceptable salt thereof;

16. The method of claim 15 wherein at least one of R¹, R² and R³ is a halo substituent.

17. The method of claim 15, wherein the compound has formula (IX):

18. The method of claim 15 wherein the compound has formula (X):

19. A method for modulating human N-type calcium channel α

_1B+SFVG subunit activity, the method comprising administering to a subject in need thereof an effective amount of a compound comprising;

a straight backbone carbon chain of C8-16C, optionally substituted with 1-15 alkyl groups (C1-C6);

said chain optionally functionalized at one terminus with halo, —

OR, SR, NR₂, —

OOCR, —

NROCR wherein R is alkyl (C1-C6), or phosphate or pyrophosphate, or functionalized wherein a terminal carbon is optionally in the form or —

COOR, —

CONR₂ or —

COR wherein R is alkyl (C1-C16); and

wherein said chain may optionally contain 1-4 π

-bonds or the epoxides thereof.