4-Azaindole compounds

Patent metadata

Field	Value
Publication number	US-10730877-B2
Application number	US-201916695303-A
Country	US
Kind code	B2
Filing date	Nov 26, 2019
Priority date	Dec 18, 2017
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

Disclosed are compounds of Formula (I)

N-oxides, or salts thereof, wherein G, A, R 1 , R 5 , and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

First claim

What is claimed is:

1. A compound of Formula (I)

N-oxide, or a salt thereof, wherein:
G is:

A is —CR x R 12 R 13 , wherein R 12 and R 13 together with the carbon atom to which they are attached form a cyclic group selected from piperidinyl substituted with zero to 3 R 12a ;
R 1 is H, C 1-3 alkyl, C 1-2 fluoroalkyl, C 1-2 hydroxyalkyl, or C 1-3 hydroxy-fluoroalkyl;
each R 2 is independently F, Cl, —CN, —OH, C 1-2 alkyl, C 1-2 fluoroalkyl, C 1-2 cyanoalkyl, or C 1-2 hydroxyalkyl;
R 2a is C 1-2 alkyl, C 1-2 fluoroalkyl, or C 1-2 hydroxyalkyl;
each R 2b is independently H, F, Cl, —CN, or C 1-2 alkyl;
each R 5 is independently F, —CN, C 1-2 alkyl, C 1-2 fluoroalkyl, or —OCH 3 ;
each R 12a is independently F, Cl, C 1-4 alkyl, C 1-2 fluoroalkyl, C 1-4 cyanoalkyl, C 1-6 hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-3 alkyl), —(CH 2 ) 1-2 C(O)NR x R x , —(CH 2 ) 1-2 S(O) 2 (C 1-2 alkyl), —(CH 2 ) 1-2 NR x R x , C 1-3 alkoxy, —NR y R y , —NR x C(O)CH 3 , —NR x S(O) 2 (C 1-2 alkyl), —C(O)(C 1-5 alkyl), —C(O)(CR x R x ) 1-2 NR y R y , R 12b , —CR x R x R 12b , —C(O)R 12b , —NR x R 12b , —NR x CR x R x R 12b , or —OR 12b ; or two R 12a and the carbon atom to which they are attached form C═O;
R 12b is azetidinyl, C 3-6 cycloalkyl, imidazolyl, morpholinyl, oxetanyl, phenyl, piperazinyl, piperazinonyl, piperidinyl, pyridinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, or triazolyl, each substituted with zero to 4 substituents independently selected from F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, C 1-2 hydroxyalkyl, C 1-2 aminoalkyl, C 1-2 alkoxy, —NR x R x , and —C(O)NR x R x ;
each R x is independently H or —CH 3 ;
each R y is independently H or C 1-6 alkyl;
n is zero, 1 or 2; and
p is zero, 1, 2, or 3.

2. The compound according to claim 1 , or N-oxide or a salt thereof, wherein:
A is —CR x R 12 R 13 , wherein R 12 and R 13 together with the carbon atom to which they are attached form a cyclic group selected from piperidinyl substituted with zero to 2 R 12a ;
R 1 is H, C 1-3 alkyl, —CHF 2 , —CF 3 , or —CH 2 OH;
each R 2 is independently F, Cl, —CN, —CH 3 , —CF 3 , or —CH 2 OH;
R 2a is C 1-2 alkyl, —CHF 2 , —CF 3 , or —CH 2 OH;
each R 2b is independently H, F, Cl, —CN, or —CH 3 ;
each R 5 is independently F, —CN, —CH 3 , —CHF 2 , —CF 3 , or —OCH 3 ;
each R 12a is independently C 1-4 alkyl, C 1-2 fluoroalkyl, C 1-2 cyanoalkyl, C 1-3 hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-2 alkyl), —(CH 2 ) 1-2 C(O)NR x R x , —(CH 2 ) 1-2 S(O) 2 (C 1-2 alkyl), —(CH 2 ) 1-2 NR x R x , C 1-3 alkoxy, —NR y R y , —NR x C(O)CH 3 , —C(O)(C 1-3 alkyl), —C(O)(CR x R x ) 1-2 NR x R x , R 12b , or —CR x R x R 12b ;
R 12b is azetidinyl, C 3-6 cycloalkyl, morpholinyl, oxetanyl, piperazinyl, piperidinyl, pyridinyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 3 substituents independently selected from F, Cl, C 1-4 alkyl, —CHF 2 , —CF 3 , —CH 2 OH, —OCH 3 , —NH 2 , and —C(O)NR x R x .

3. The compound according to claim 1 , or N-oxide or a salt thereof, wherein:
A is —CR x R 12 R 13 , wherein R 12 and R 13 together with the carbon atom to which they are attached form a cyclic group selected from piperidinyl substituted with zero to 1 R 12a ;
R 1 is —CH 3 or —CH(CH 3 ) 2 ;
each R 2 is independently —CH 3 or —OCH 3 ;
R 2a is —CH 3 ;
each R 2b is independently H, Cl, or —CH 3 ;
R 5 is independently F or —CH 3 ;
R 12a is —CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 CN, —CH 2 C(CH 3 ) 2 OH, —CH 2 C(O)NHR x R x , —C(O)CH 2 N(CH 3 ) 2 , —CH 2 CH 2 S(O) 2 CH 3 , oxetanyl, tetrahydropyranyl, or isobutylpiperidinyl;
m is zero or 1; and
p is zero, 1, or 2.

4. The compound according to claim 1 , or N-oxide or a salt thereof, having the structure

5. The compound according to claim 4 , or N-oxide or a salt thereof, wherein:
G is:

6. The compound according to claim 1 , or N-oxide or a salt thereof, having the structure

7. The compound according to claim 1 , or N-oxide or a salt thereof, having the structure

8. The compound according to claim 1 , or N-oxide or a salt thereof, wherein:
G is:

9. The compound according to claim 1 , or N-oxide or a salt thereof, wherein:
G is:

10. The compound according to claim 1 , or N-oxide or a salt thereof, wherein:
G is:

11. The compound according to claim 1 , or N-oxide or a salt thereof, wherein said compound is:
2-(3,4-dimethoxyphenyl)-5-(1′-isobutyl-[,4′-bipiperidin]-4-yl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (5);
6-(6-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (11);
2-(2,6-dimethylpyridin-4-yl)-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (512);
5-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1-methylpyridin-2(1H)-one (513);
6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-2,4-dimethylpyridazin-3 (2H)-one (514);
5-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one (515);
6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (516, 518);
6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyltetrazolo[1,5-a]pyridine (517);
5-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3,4-trimethylpyridin-2(1H)-one (519);
6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine (520);
6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (521);
2-(2,6-dimethylpyridin-4-yl)-3-isopropyl-6-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (522);
6-(3-isopropyl-6-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (523);
6-(6-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (524);
6-(3-isopropyl-6-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (525);
2-(3,4-dimethoxyphenyl)-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (526);
5-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one (527);
5-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)-1,3-dimethylpyridin-2(1H)-one (528);
2-(4-(2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (529);
2-(4-(2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (

Assignees

• Bristol Myers Squibb Co

Inventors

• Dyckman Alaric J
• Dodd Dharmpal S
• Mussari Christopher P
• Sherwood Trevor C
• Whiteley Brian K
• Gilmore John L
• Kumar Sreekantha Ratna
• Pasunoori Laxman
• Srinivas Pitani Veera Venkata
• Duraisamy Srinivasan Kunchithapatham
• Hegde Subramanya
• Anumula Rushith Kumar

Classifications

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D495/10

  Spiro-condensed systems · CPC title

• C07D491/107

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D471/08

  Bridged systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title