Substituted phenyl alkanoic acid compounds as GPR120 agonists and uses thereof

Patent metadata

Field	Value
Publication number	US-10273230-B2
Application number	US-201515328450-A
Country	US
Kind code	B2
Filing date	Jul 23, 2015
Priority date	Jul 25, 2014
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present invention relates to substituted phenyl alkanoic acid compounds designated as the compound of Formula (I) (as described herein) or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N-oxide, a S-oxide or a carboxylic acid isostere thereof; which are GPR120 agonists. The present invention also relates to a pharmaceutical composition of compound of Formula (I) for the treatment of diseases or disorder mediated by GPR120.

First claim

We claim:

1. A compound of Formula (I)

or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt, a prodrug, an N-oxide, a S-oxide or a carboxylic acid isostere thereof;
wherein:
Ring A is 5- to 12-membered carbocycle, 5- to 12-membered heterocyclyl; (C 6 -C 10 )aryl, or 5- to 12-membered heteroaryl; provided that when q is 1 or 2, and W is a bond, then (C 6 -C 10 )aryl excludes naphthyl;
Ring B is 5- to 12-membered carbocycle;
Ring C is (C 6 -C 10 )aryl;
W represents a bond, —(CR 5 R 6 ) p —, —O—, —S— or —NR 7 —;
X is —CR 5 R 6 —X 1 — or —X 1 —CR 5 R 6 —, wherein X 1 is O, S or NR 7
Y is —(C(R 4 ) 2 ) q —;
Q is —CO 2 M, —CONH 2 , —CONH[(C 1 -C 6 )alkyl], —CON[(C 1 -C 6 )alkyl] 2 , —CONHSO 2 (C 1 -C 6 )alkyl or a carboxylic acid isostere;
M is hydrogen, deuterium or (C 1 -C 6 )alkyl;
represents a single bond or a double bond;
R 1 at each occurrence is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy, (C 3 -C 10 )cycloalkyl, heterocyclyl, (C 6 -C 10 )aryl, heteroaryl, (C 6 -C 10 )aryloxy, cyano, oxo, —NR 7 R 8 , —C(O)NR 7 R 8 , —C(S)NR 7 R 8 , —S(O) t R 9 and —C(O)R 10 ;
R 2 at each occurrence is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy, (C 3 -C 10 )cycloalkyl, heterocyclyl, (C 6 -C 10 )aryl, heteroaryl, (C 6 -C 10 )aryloxy, cyano, oxo, —NR 7 R 8 , —C(O)NR 7 R 8 , —C(S)NR 7 R 8 , —S(O) t R 9 and —C(O)R 10 ;
R 3 at each occurrence is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy, (C 3 -C 10 )cycloalkyl, heterocyclyl, (C 6 -C 10 )aryl, heteroaryl, cyano, −NR 7 R 8 , —S(O) t R 9 and —C(O)R 10 ;
R 4 at each occurrence is independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl and halogen; or
two R 4 groups, together with the carbon atom to which they are attached can combine to form a (C 3 -C 10 )cycloalkyl or heterocyclyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, deuterium, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl and halogen; or
R 5 and R 6 together with the carbon atom to which they are attached can combine to form
i) 5- to 12-membered carbocycle or
ii) 5- to 12-membered heterocyclyl containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S;

R 7 and R 8 are independently selected from the group consisting of hydrogen, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, heterocyclyl, (C 6 -C 10 )aryl, heteroaryl, (C 6 -C 10 )aryloxy, —S(O) t R 9 ; or
R 7 and R 8 , together with the nitrogen atom to which they are attached combine to form heterocyclyl;
R 9 and R 10 are independently selected from the group consisting of hydrogen, hydroxy, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, heterocyclyl, (C 6 -C 10 )aryl, heteroaryl and —NR 7 R 8 ;
m is 0, 1, 2 or 3;
n is 0, 1, 2 or 3;
o is 0, 1 or 2;
p is 1 or 2;
q is 1, 2, 3 or 4;
t is 0, 1 or 2;
wherein:

(C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halogen, halo(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, heterocyclyl, heteroaryl, amino, cyano, nitro, —NH(C 1 -C 6 )alkyl, —N[(C 1 -C 6 )alkyl] 2 , —C(O)(C 1 -C 6 )alkyl, —C(O)O(C 1 -C 6 )alkyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 )alkyl, —C(O)N[(C 1 -C 6 )alkyl] 2 and —C(O)NHSO 2 (C 1 -C 6 )alkyl;
(C 3 -C 10 )cycloalkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halogen, halo(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, amino, cyano and nitro;
carbocycle is a 5- to 12-membered ring which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, hydroxy, halogen, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 6 -C 10 )aryl, (C 3 -C 10 )cycloalkyl, heteroaryl, heterocyclyl, amino, cyano, nitro, —C(O)O(C 1 -C 6 )alkyl, —C(O)NR 7 R 8 and —S(O) t R 9 ; wherein R 7 , R 8 , R 9 and t are as defined above;
heterocyclyl is a 5- to 12-membered ring which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halogen, halo(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, heterocyclyl, heteroaryl, amino, cyano, nitro, oxo, —NR 7 R 8 , —C(O)NR 7 R 8 , —S(O) t R 9 and —C(O)R 10 ; wherein R 7 , R 8 , R 9 , R 10 and t are as defined above;
(C 6 -C 10 )aryl is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halogen, halo(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, heterocyclyl, heteroaryl, amino, cyano, nitro, —C(O)O(C 1 -C 6 )alkyl, —C(O)NR 7 R 8 and —S(O) t R 9 ; wherein R 7 , R 8 , R 9 and t are as defined above;
heteroaryl is a 5- to 12-membered ring which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halogen, halo(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, heterocyclyl, heteroaryl, amino, cyano, nitro, —C(O)NR 7 R 8 and —S(O) t R 9 ; wherein R 7 , R 8 , R 9 and t are as defined above.

2. The compound according to claim 1 , wherein Ring A is 5- to 12-membered carbocycle which is unsubstituted or substituted with one or more groups of R 1 ; wherein R 1 is as defined above; or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt, a prodrug, an N-oxide, a S-oxide or a carboxylic acid isostere thereof.

3. The compound according to claim 1 , wherein Ring A is 5- to 12-membered heterocyclyl containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S, wherein said heterocyclyl is unsubstituted or substituted with one or more groups of R 1 , wherein R 1 is as defined above; or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt, a prodrug, an N-oxide, a S-oxide or a carboxylic acid isostere thereof.

4. The compound according to claim 1 , wherein Ring A is (C 6 -C 10 )aryl; which is unsubstituted or substituted with one or more groups of R 1 ; wherein R 1 is as defined above; or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt, a prodrug, an N-oxide, a S-oxide or a carboxylic acid isostere thereof.

5. The compound according to claim 1 , wherein Ring A is 5- to 12-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S, wherein said heteroaryl is unsubstituted or which is substituted with one or more groups of R 1 ; wherein R 1 is as defined above; or a tautomer, a stereoisomer, a geometrical isomer, a pharmaceutically acceptable salt,

Assignees

• Piramal Entpr Ltd

Inventors

• Kumar Sanjay
• Sharma Rajiv
• Deore Vijaykumar Bhagwan
• Yewalkar Nilambari Nilkanth

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07D213/30

  Oxygen atoms · CPC title

• C07D333/16

  by oxygen atoms · CPC title