Protein kinase D inhibitors

Patent metadata

Field	Value
Publication number	US-9840515-B2
Application number	US-201113992546-A
Country	US
Kind code	B2
Filing date	Dec 8, 2011
Priority date	Dec 9, 2010
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

Compounds according to Formula (I), are potent inhibitors of protein kinase D (pan-PKD) activity. PKD controls key signaling cascades in cells, affecting cell proliferation, gene transcription, and protein trafficking. Accordingly, pharmaceutically acceptable compositions of the inventive compounds are candidate therapeutics for pathological conditions conditioned by changes in PKD activity.

First claim

What is claimed is:

1. A compound according to Formula I,

wherein
R 1 , R 2 , R 3 , and R 4 are each independently selected from the group consisting of hydrogen, straight or branched chain (C 1 -C 6 )alkyl, (C 2 -C 6 )alkene, halogen, —OH, —OR′, —OC(O)CH 3 , (C 1 -C 6 )alkoxy, —N 3 , —NR′R″, isocyanate, isothiocyanate, straight or branched (C 1 -C 6 )haloalkyl and straight or branched (C 1 -C 6 )haloalkoxy;
R 5 is selected from the group consisting of hydrogen, a straight or branched chain (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-NH 2 , (C 1 -C 6 )alkoxy, and —C(O)—(C 1 -C 6 )alkyl;
each of X and X′ is a —C— or —N—;
Y is —S—;
Z is —S—; and
n is 1;
wherein R′, R″, R a , R b and R d are each independently selected from the group consisting of H, straight or branched (C 1 -C 6 )alkyl, (C 2 -C 6 )alkene, (C 2 -C 6 )alkenyloxy, halogen, —OH, —OC(O)CH 3 , —C(O)CH 3 , —C(O)CH 2 -halide, straight or branched (C 1 -C 6 )haloalkyl, and benzyl,
wherein R 1 is only present when X is C, and R 3 is only present when X′ is C,
or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof.

2. The compound according to claim 1 , wherein R 2 is —OH.

3. The compound according to claim 1 , wherein R 2 is (C 1 -C 6 )alkoxy.

4. The compound according to claim 3 , wherein R 2 is methoxy.

5. The compound according to claim 1 , wherein R 2 is an azide.

6. The compound according to claim 1 , wherein each of X and X′ is —N—.

7. The compound according to claim 1 , wherein each of X and X′ is —CH—.

8. The compound according to claim 1 , wherein R 2 is H.

9. The compound according to claim 1 that is selected from the following table:

10. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound according to claim 1 , or a pharmaceutically acceptable salt, tautomer, or prodrug thereof; and a pharmaceutically acceptable carrier.

11. A method for inhibiting PKD1 in a cell, comprising contacting the cell with at least one compound according to claim 1 .

Assignees

• Wipf Peter
• Wang Qiming Jane
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Wipf Peter
• Wang Qiming Jane

Classifications

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D491/147

  the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom · CPC title

• A61P35/00

  Antineoplastic agents · CPC title