Calcium channel agonists

Patent metadata

Field	Value
Publication number	US-9796714-B2
Application number	US-201414892184-A
Country	US
Kind code	B2
Filing date	May 19, 2014
Priority date	May 20, 2013
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I:

wherein each bond depicted as “ ” is a single bond or a double bond as needed to satisfy valence requirements; Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 independently are nitrogen or carbon; R 1 and R 3 are alkyl; R 2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R 4 is alkyl or hydroxyalkyl.

First claim

We claim:

1. A compound having a structure according to formula I or a pharmaceutically acceptable salt thereof:

wherein each bond depicted as “------” is a single bond or a double bond as needed to satisfy valence requirements;
Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 independently are nitrogen or carbon;
R 1 and R 3 are alkyl;
R 2 is substituted or unsubstituted thiophenyl methyl; and
R 4 is alkyl or hydroxyalkyl.

2. The compound of claim 1 , wherein two of Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are nitrogen.

3. The compound of claim 1 , wherein Z 1 and Z 3 are nitrogen, and Z 2 , Z 4 , and Z 5 are carbon.

4. The compound of claim 1 , wherein R 3 is ethyl.

5. The compound of claim 1 , wherein R 4 is —CH 2 OH.

6. The compound of claim 1 , wherein R 1 is n-alkyl.

7. The compound of claim 1 , wherein R 1 is C 1 -C 3 alkyl.

8. The compound of claim 7 where R 1 is n-propyl.

9. The compound of claim 1 , wherein the structure is:

10. A pharmaceutical composition comprising:
at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof; and
at least one pharmaceutically acceptable additive.

11. The compound of claim 1 , wherein Z 3 and Z 4 are nitrogen, and Z 1 , Z 2 and Z 5 are carbon.

12. The compound of claim 1 , wherein R 2 is:

13. The compound of claim 2 , wherein R 2 is:

14. The compound of claim 3 , wherein R 2 is:

15. The compound of claim 1 , wherein R 1 is substituted alkyl.

16. The compound of claim 3 , wherein R 1 is substituted alkyl.

17. The compound of claim 14 , wherein R 1 is substituted alkyl.

18. The compound of claim 1 , wherein R 1 is cyclic alkyl.

19. The compound of claim 14 , wherein R 1 is cyclic alkyl.

20. The compound of claim 11 , wherein R 1 is substituted alkyl.

21. The compound of claim 1 , wherein Z 1 , Z 2 and Z 3 are nitrogen, and Z 4 and Z 5 are carbon.

22. The compound of claim 21 , wherein R 1 is substituted alkyl.

Assignees

• Wipf Peter
• Meriney Stephen D
• Liang Mary
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Wipf Peter
• Meriney Stephen D
• Liang Mary

Classifications

• C07D473/16 Primary

  two nitrogen atoms · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61P21/04

  for myasthenia gravis · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title