Bicyclic GPR119 modulators

Patent metadata

Field	Value
Publication number	US-9000175-B2
Application number	US-201113989611-A
Country	US
Kind code	B2
Filing date	Nov 24, 2011
Priority date	Nov 26, 2010
Publication date	Apr 7, 2015
Grant date	Apr 7, 2015

Abstract

The present invention relates to compounds of Formula (I) that are useful for treating, preventing and/or managing the diseases, disorders, syndromes or conditions associated with the modulation of GPR119 receptor activity. The invention also relates to the process for preparation of the compounds, pharmaceutical compositions thereof. The invention further relates to methods of treating, preventing and/or managing diseases, disorders syndromes or conditions associated with the modulation of GPR119 receptor by using either alone or in combinations of Formula (I).

First claim

The invention claimed is:

1. A compound of Formula (II):

or pharmaceutically acceptable salt thereof;
wherein,
is a double bond;
R 2 is selected from the group consisting of hydrogen, alkyl, and halo;
R 3 is selected from the group consisting of —S(O) p R a , —C(O)OR a , —(CH 2 ) q C(O)NR a R b , —(CH 2 ) q N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)NR a R b , —S(O) 2 NR a R b , —N(R a )S(O) 2 R b , —CN, alkoxy, hydroxyalkyl, heterocyclyl and heteroaryl;
R a and R b are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxy, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, aryl, heteroaryl, arylalkyl, and heterocyclyl; or R a and R b may join together with the nitrogen atom to which they are attached to form a heterocyclic ring;
Z is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, haloalkyl, hydroxyalkyl, —(CH 2 ) q C(O)OR a , —(CH 2 ) q C(O)R a , —C(O)(CH 2 ) q NR a R b , —(CH 2 ) q C(O)NR a R b , —S(O) 2 R a , —S(O) 2 NR a R b , —C(O)CR,R d R e and —(CH 2 ) q CR c R d R e ;
R c R d and R e are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heterocyclyl; or R c and R d may join together with the carbon atom to which they are attached to form a 3 to 7 membered carbocyclic or heterocyclic ring;
R 5 , R 6 , R 7 , R 8 are hydrogen; or
any two of R 5 , R 6 , R 7 , R 8 and Z may join together to form a cycloalkyl or heterocyclyl ring;
X is selected from the group consisting of —(CR 10 R 11 ) q O(CR 10 R 11 ) t —, —(CR 10 R 11 ) q S(O) p (CR 10 R 11 ) t — and —(CR 10 R 11 ) q NR 9 (CR 10 R 11 ) t —;
R 9 is hydrogen or alkyl;
R 10 and R 11 are hydrogen;
‘m’, ‘n’ and ‘p’ are each independently selected from 0, 1 or 2;
‘q’ is an integer ranging from 0 to 4, both inclusive;
‘t’ is an integer ranging from 0 to 4, both inclusive; and
wherein, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, heterocyclic ring, alkoxy, hydroxyalkyl, haloalkyl, arylalkyl, heterocyclylalkyl, heteroarylalkyl and carbocyclic ring wherever they occur may optionally be substituted with one or more substituents independently selected from hydroxy, halo, cyano, nitro, oxo (═O), thio (═S), alkyl, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heteroaryl, heterocyclic ring, heterocyclylalkyl, heteroarylalkyl, —C(O)OR x , —C(O)R x , —C(S)R x , —C(O)NR x R y , —NR x C(O)NR y R z , —N(R x )S(O)R y , —N(R x )S(O) 2 R y , —NR x R y , —NR x C(O)R y , —NR x C(S)R y , —NR x C(S)NR y R z , —S(O)NR x R y , —S(O) 2 NR x R y , —OR x , —OC(O)R x , —OC(O)NR x R y , —R x C(O)OR y , —R x C(O)NR y R z , —R x C(O)R y , —SR X , —S(O)R x , and —S(O) 2 R x ; wherein each occurrence of R x , R y and R z are independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic ring, heterocyclylalkyl ring and heteroarylalkyl.

2. The compound of claim 1 , having the Formula (V):

or pharmaceutically acceptable salt thereof;
wherein,
is a double bond;
X is selected from the group consisting of —(CR 10 R 11 ) q O(CR 10 R 11 ) t —, —(CR 10 R 11 ) q S(O) p (CR 10 R 11 ) t — and —(CR 10 R 11 ) q NR 9 (CR 10 R 11 ) t —;
Z is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, haloalkyl, hydroxyalkyl, —(CH 2 ) q C(O)OR a , —(CH 2 ) q C(O)R a , —C(O)(CH 2 ) q NR a R b , —(CH 2 ) q C(O)NR a R b , —S(O) 2 R a , —S(O) 2 NR a R b , —C(O)CR c R d R e and —(CH 2 ) q CR c R d R e ;
R 2 ,is selected from the group consisting of hydrogen, alkyl, and halo;
R 3 is selected from the group consisting of —S(O) p R a , —C(O)OR a , —(CH 2 ) q C(O)NR a R b , —(CH 2 ) q N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)NR a R b , —S(O) 2 NR a R b , —N(R a )S(O) 2 R b , —CN, alkoxy, hydroxyalkyl, heterocyclyl and heteroaryl;
R a and R b are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxy, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, aryl, heteroaryl, arylalkyl, and heterocyclyl; or R a and R b may join together with the nitrogen atom to which they are attached to form a heterocyclic ring;
R c , R d and R e are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heterocyclyl; or R c and R d may join together with the carbon atom to which they are attached to form a 3 to 7 membered carbocyclic or heterocyclic ring;
R 9 is hydrogen or alkyl;
R 10 and R 11 are hydrogen;
‘p’ is each independently selected from 0, 1 or 2;
‘q’ is each an integer ranging from 0 to 4, both inclusive; and
‘t’ is each an integer ranging from 0 to 4, both inclusive.

3. The compound of claim 1 , wherein:
R 3 is hydroxyalkyl, —C(O)OR a , —S(O) 2 R a , —C(O)NR a R b , —N(R a )C(O)R b , —CH 2 N(R a )C(O)R b , —N(R a )C(O)OR b , —N(R a )C(O)NR a R b , —S(O) 2 NR a R b , —N(R a )S(O) 2 R b , heterocyclyl; and
R a and R b are each independently a hydrogen, alkyl, haloalkyl, cycloalkyl, hydroxyalkyl, aryl, heteroaryl or heterocyclyl; or R a and R b may join together with the nitrogen atom to which they are attached to form a heterocyclic ring.

4. The compound of claim 1 , wherein R 3 is substituted or unsubstituted heteroaryl or heterocyclyl.

5. The compound of claim 4 , wherein heteroaryl is oxazole, oxadiazole, triazole or tetrazole.

6. The compound of claim 4 , wherein heterocyclyl is pyrrolidine, pyrrolidine-2-one or oxazolidin-2-one.

7. The compound of claim 3 , wherein X is —(CR 10 R 11 ) q O(CR 10 R 11 ) t — or —CR 10 R 11 ) q NR 9 (CR 10 R 11 ) t —; ‘q’ is 0 or 1; ‘t’ is 0 or 1; and each of R 10 and R 11 are hydrogen.

8. The compound of claim 1 , wherein Z is alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, hydroxyalkyl, —C(O)OR a , —C(O)R a , —C(O)CR c R d R e , —(CH 2 ) 0-2 CR c R d R e , —S(O) 2 R a or —S(O) 2 NR a R b wherein R a , R b , R c , R d and R e are each independently a hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heterocyclyl; or R a and R b may join together with the nitrogen atom to which they are attached to form a heterocyclic ring; or R c and R d may join together with the carbon atom to which they are attached to form a 3 to 7 membered carbocyclic or heterocyclic ring; ‘m’ is 0 or 1; and ‘n’ is 0 or 1.

9. The compound of claim 1 , wherein:
R 2 is hydrogen or halogen;
R 3 is —S(O) 2 R a , —C(O)NR a R b , —N(R a )C(O)R b , —N(R a )C(O)OR b , heterocyclyl, or heteroaryl, wherein R a and R b are each independently a hydrogen or alkyl;
X is —O, or —NH—;
Z is alkyl, haloalkyl, heteroaryl, heterocyclyl, —C(O)Oalkyl, —C(O)CR c R d R e , or —(CH 2 ) 0-2 CR c R d R e ; R 5 , R 6 , R 7 and R 8 are hydrogen; ‘m’ is 1; and ‘n’ is 1.

10. The compound of claim 1 , which is selected from:
tert-Butyl-4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidine-1-carboxylate;
1-(5-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)oxy)pyridin-2-yl)-5-(methylsulfonyl)-1H-indole;
3-Isopropyl-5-(4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)ox

Assignees

• Thotapally Rajesh
• Kachi Onkar Gangaram
• Rodge Atish Harishchandra
• Pathak Ashok Bhau
• Kardile Bhavana Shrirang
• Sindkhedkar Milind Dattatraya
• Palle Venkata P
• Kamboj Rajender Kumar
• Lupin Ltd

Inventors

• Thotapally Rajesh
• Kachi Onkar Gangaram
• Rodge Atish Harishchandra
• Pathak Ashok Bhau
• Kardile Bhavana Shrirang
• Sindkhedkar Milind Dattatraya
• Palle Venkata P
• Kamboj Rajender Kumar

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title