Somatostatin modulators and uses thereof

Patent metadata

Field	Value
Publication number	US-2017002001-A1
Application number	US-201615186086-A
Country	US
Kind code	A1
Filing date	Jun 17, 2016
Priority date	Jul 1, 2015
Publication date	Jan 5, 2017
Grant date	—

Abstract

Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

First claim

What is claimed is:

1 . A compound that has the structure of Formula (A), or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, diastereomeric mixture, individual enantiomers or prodrug thereof:

wherein:
A 1 and A 2 are independently N or CR A , provided that A 1 and A 2 are not N at the same time;
each R A is independently hydrogen, unsubstituted or substituted C 1 -C 4 alkyl, unsubstituted or substituted C 1 -C 4 fluoroalkyl, unsubstituted or substituted C 1 -C 4 alkoxy, unsubstituted or substituted C 1 -C 4 fluoroalkoxy, —CN, —OH, —CO 2 R 17 , —C(═O)NR 17 R 18 , —NR 17 R 18 , —NR 17 C(═O)NHR 18 , —NR 17 C(═O)(C 1 -C 4 alkyl), —C(═NOR 17 )R 18 , —SR 17 , —S(═O)(C 1 -C 4 alkyl), —SO 2 (C 1 -C 4 alkyl), or —SO 2 NR 17 R 18 ;

B 1 and B 2 are independently N or CR B , provided that B 1 and B 2 are not N at the same time;
each R B is independently hydrogen, unsubstituted or substituted C 1 -C 4 alkyl, unsubstituted or substituted C 1 -C 4 fluoroalkyl, unsubstituted or substituted C 1 -C 4 alkoxy, unsubstituted or substituted C 1 -C 4 fluoroalkoxy, —CN, —OH, —CO 2 R 17 , —C(═O)NR 17 R 18 , —NR 17 R 18 , —NR 17 C(═O)NHR 18 , —NR 17 C(═O)(C 1 -C 4 alkyl), —C(═NOR 17 )R 18 , —SR 17 , —S(═O)(C 1 -C 4 alkyl), —SO 2 (C 1 -C 4 alkyl), or —SO 2 NR 17 R 18 ;

R 1 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bicyclic heterocycle, —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic carbocycle or unsubstituted or substituted bicyclic carbocycle), or —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic heterocycle or unsubstituted or substituted bicyclic heterocycle), wherein if R 1 is substituted then R 1 is substituted with 1-2 R 13 and 0-2 R 14 ;
R 2 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bicyclic heterocycle, —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic carbocycle or unsubstituted or substituted bicyclic carbocycle), or —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic heterocycle or unsubstituted or substituted bicyclic heterocycle), wherein if R 2 is substituted then R 2 is substituted with 1-2 R 15 and 0-2 R 16 ;
R 3 and R 4 are independently hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, or unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein any substituted group of R 3 and R 4 is substituted with 1-4 R 12 ;
or R 3 and R 4 are taken together with the nitrogen atom with to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R 12 ;
R 5 , R 6 , R 7 , R 8 , R 10 , and R 11 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, and unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bicyclic heterocycle, —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic carbocycle or unsubstituted or substituted bicyclic carbocycle), or —(C 1 -C 4 alkylene)-(unsubstituted or substituted monocyclic heterocycle or unsubstituted or substituted bicyclic heterocycle), wherein if R 5 , R 6 , R 7 , R 8 , R 10 , and R 11 is substituted then R 5 , R 6 , R 7 , R 8 , R 10 , and R 11 is substituted with 1-2 R 15 and 0-2 R 16 ;
X is NR 9 , O, or CR 9 R 19 ;
R 9 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted benzyl, wherein if R 9 is substituted then R 9 is substituted with 1-4 R 12 ;
R 19 is hydrogen, or unsubstituted or substituted C 1 -C 6 alkyl, wherein if R 19 is substituted then R 19 is substituted with 1-4 R 12 ;
or R 4 and any one of R 5 , R 7 , R 9 , or R 11 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R 12 ;
or R 5 and R 6 are taken together with the carbon atom with to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered carbocyclic ring, wherein if the carbocyclic ring is substituted then the carbocyclic ring is substituted with 1-4 R 12 ;
or R 5 and any one of R 7 , R 9 , or R 11 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R 12 ;
or R 7 and one of R 9 or R 11 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R 12 ;
or R 9 and R 11 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R 12 ;
each R 12 is independently halogen, heterocycle, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 aminoalkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 fluoroalkoxy, —CN, —OR 17 , —CO 2 R 17 , —C 1 -C 4 alkylCO 2 R 17 , —C(═O)NR 17 R 18 , —NR 17 R 18 , —NR 17 C(═O)NHR 18 , —NR 17 C(═O)R 18 , —C(═NOR 17 )R 18 , —SR 17 , —S(═O)(C 1 -C 4 alkyl), —SO 2 (C 1 -C 4 alkyl), or —SO 2 NR 17 R 18 ;
each of R 13 and R 14 is independently hydrogen, halogen, unsubstituted or substituted C 1 -C 4 alkyl, unsubstituted or substituted C 1 -C 4 alkoxy, unsubstituted or substituted C 1 -C 4 fluoroalkyl, unsubstituted or substituted C 1 -C 4 fluoroalkoxy, unsubstituted or substituted heterocycle, —CN, —OH, —CO 2 R 17 , —C(═O)NR 17 R 18 , —NR 17 R 18 , —NR 17 C(═O)R 18 , —NR 17 C(═O)NHR 18 , —C(═NOR 17 )R 18 , —S(═O)(C 1 -C 4 alkyl), —SO 2 (C 1 -C 4 alkyl), or —SO 2 NR 17 R 18 , wherein if any group of R 13 and R 14 is substituted then the substituted group of R 13 and R 14 is substituted with 1-4R 12 ;
each of R 15 and R 16 is independently hydrogen, halogen, unsubstituted or substituted C 1 -C 4 alkyl, unsubstituted or substituted C 1 -C 4 alkoxy, unsubstituted or substituted C 1 -C 4 fluoroalkyl, unsubstituted or substituted C 1 -C 4 fluoroalkoxy, unsubstituted or substituted heterocycle, —CN, —OH, —CO 2 R 17 , —C(═O)NR 17 R 18 , —NR 17 R 18 , —NR 17 C(═O)R 18 , —NR 17 C(═O)NHR 18 , —C(═NOR 17 )R 18 , —SR 17 , —S(═O)(C 1 -C 4 alkyl), —SO 2 (C 1 -C 4 alkyl), or —SO 2 NR 17 R 18 , wherein if any group of R 15 and

Assignees

• Crinetics Pharmaceuticals Inc

Inventors

• Zhu Yunfei
• Zhao Jian
• Chen Zhiyong

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title