Amino-pyrimidine skeletal muscle modulators

Patent metadata

Field	Value
Publication number	US-9730886-B2
Application number	US-201514594315-A
Country	US
Kind code	B2
Filing date	Jan 12, 2015
Priority date	Apr 23, 2010
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

Provided are compounds of Formula I:

or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X and m are as defined herein.

Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof.
Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from the group consisting of hydrogen, halogen, CN, C 1-6 alkyl, C 1-6 haloalkyl, C(O)OR a , C(O)NR b R c , OR a , and C 6-10 aryl;
R 2 is selected from the group consisting of C 6-10 aryl, and 5-10 membered heteroaryl, wherein each of the C 6-10 aryl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, (CH 2 ) n OR a , (CH 2 ) n OC(O)R a , (CH 2 ) n OC(O)OR a , (CH 2 ) n OC(O)NR b R c , (CH 2 ) n NR b R c , (CH 2 ) n NR d C(O)R a , (CH 2 ) n NR d C(O)OR a , (CH 2 ) n NR d C(O)NR b R c , (CH 2 ) n NR d C(O)C(O)NR b R c , (CH 2 ) n NR d C(S)R a , (CH 2 ) n NR d C(S)OR a , (CH 2 ) n NR d C(S)NR b R c , (CH 2 ) n NR d C(NR e )NR b R c , (CH 2 ) n NR d S(O)R a , (CH 2 ) n NR d SO 2 R a , (CH 2 ) n NR d SO 2 NR b R c , (CH 2 ) n C(O)R a , (CH 2 ) n C(O)OR a , (CH 2 ) n C(O)NR b R c , (CH 2 ) n C(S)R a , (CH 2 ) n C(S)OR a , (CH 2 ) n C(S)NR b R c , (CH 2 ) n C(NR e )NR b R c , (CH 2 ) n SR a , (CH 2 ) n S(O)R a , (CH 2 ) n SO 2 R a , (CH 2 ) n SO 2 NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, (CH 2 ) n C 3-8 cycloalkyl, (CH 2 ) n C 6-10 aryl and (CH 2 ) n 5-10 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, (CH 2 ) n C 3-8 cycloalkyl, (CH 2 ) n C 6-10 aryl and (CH 2 ) n 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R f substituents;
R 3 is selected from the group consisting of hydrogen, halogen, CN, C 1-6 alkyl, C 1-6 haloalkyl, C(O)OR a , C(O)NR b R c , OR a , and C 6-10 aryl;
R 4 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R a , C(O)OR a , C(O)NR b R c and SO 2 R a ;
R 5 is selected from the group consisting of halogen, C 1-6 alkyl and C 1-6 haloalkyl;
R 6 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl and C 1-6 haloalkyl;
R 7 is selected from the group consisting of C 6-10 aryl and 5-10 membered heteroaryl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR a , OC(O)R a , OC(O)OR a , OC(O)NR b R c , NR b R c , NR d C(O)R a , NR d C(O)OR a , NR d C(O)NR b R c , NR d C(O)C(O)NR b R c , NR d C(S)R a , NR d C(S)OR a , NR d C(S)NR b R c , NR d C(NR e )NR b R c , NR d S(O)R a , NR d SO 2 R a , NR d SO 2 NR b R c , C(O)R a , C(O)OR a , C(O)NR b R c , C(S)R a , C(S)OR a , C(S)NR b R c , C(NR e )NR b R c , SR a , S(O)R a , SO 2 R a , SO 2 NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R f substituents;
R 8 and R 9 , at each occurrence, are each independently selected from the group consisting of hydrogen, halogen and C 1-6 alkyl;
X is a bond;
or alternatively, X, R 2 and R 3 , together with the carbon atoms to which they are bound, form a 5-6 membered ring optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and optionally containing one or more double bonds, and optionally substituted with 1, 2, 3, 4 or 5 R f substituents;
R a , at each occurrence, is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R f substituents;
R b and R c , at each occurrence, are each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl, 5-10 membered heteroaryl, C(O)R g , C(O)OR g , C(O)NR i R j and SO 2 R g , wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R f substituents;
R d , at each occurrence, is independently selected from the group consisting of hydrogen and C 1-6 alkyl;
R e , at each occurrence, is independently selected from the group consisting of hydrogen, CN, OH, C 1-6 alkoxy, C 1-6 alkyl and C 1-6 haloalkyl;
R f , at each occurrence, is independently selected from the group consisting of halogen, CN, OR h , OC(O)R h , OC(O)OR h , OC(O)NR i R j , NR i R j , NR d C(O)R h , NR d C(O)OR h , NR d C(O)NR i R j , NR d C(O)C(O)NR i R j , NR d C(S)R h , NR d C(S)OR h , NR d C(S)NR i R j , NR d C(NR e )NR i R j , NR d S(O)R h , NR d SO 2 R h , NR d SO 2 NR i R j , C(O)R h , C(O)OR h , C(O)NR i R j , C(S)R h , C(S)OR h , C(S)NR i R j , C(NR e )NR i R j , SR h , S(O)R h , SO 2 R h , SO 2 NR i R j , C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R k substituents;
or two R f substituents bound to a single carbon atom, together with the carbon atom to which they are both bound, form a group selected from the group consisting of carbonyl, C 3-8 cycloalkyl and 3-8 membered heterocycloalkyl;
R g , at each occurrence, is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, phenyl, naphthyl, and C 7-11 aralkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, OH, C 1-6 alkoxy, C 1-6 alkyl and C 1-6 haloalkyl;
R h , at each occurrence, is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R k substituents;
R i and R j , at each occurrence, are each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C 6-10 aryl, C 7-11 aralkyl, 5-10 membered heteroaryl, C(O)R g , and C(O)OR g , wherein each of the C 1-6 alkyl, C 1-6 halo

Assignees

• Cytokinetics Inc

Inventors

• Yang Zhe
• Muci Alex R
• Warrington Jeffrey
• Bergnes Gustave
• Morgan Bradley P
• Chuang Chihyuan
• Romero Antonio
• Collibee Scott
• Qian Xiangping
• Lu Pu-Ping

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title