Granted Patent B2

US 12,486,267 · App. 18/042,036 · Granted Dec 2, 2025

Inventors: David S. Yoon (Ambler, PA); Alicia Regueiro-Ren (New Hope, PA); Andrew P. Degnan (Jamison, PA); Gang Wu (Princeton, NJ)

Assignee: Bristol-Myers Squibb Company

C07D471/04

Abstract

Claims (191)

1 . A compound of Formula (II):

or stereoisomer, tautomer, solvate or salt thereof, wherein:

X is N or CR 3 ;

one of Q 1 and Q 2 is A and the other of Q 1 and Q 2 is R 5 ;

G is phenyl substituted with —S(O) 2 CH 3 , —S(O) 2 (phenyl), —S(O) 2 NR x R x , or —S(O)(NH)NR x R x ;

A is cyclohexyl, piperidinyl, phenyl, pyridinyl, pyrimidinyl, 6-azabicyclo[3.2.1]octanyl, or azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 and zero to 1 R 4b ;

L is a bond, —CR x R x — or —C(O)(CR x R x ) 0-2 —;

R 3 is hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

R 4 is:

(i) —N(CH 3 ) 2 ;

(ii) pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, pyridinyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with zero to 2 R 4a ; or

each R 4a is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —(CH 2 ) 0-2 O(C 1-2 alkyl), C 3-6 cycloalkyl, —CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(C 3-6 cycloalkyl), —C(O)(phenyl), —C(O)CH 2 (C 3-6 cycloalkyl), —C(O)CH 2 (phenyl), —C(O)O(C 1-4 alkyl), oxetanyl, tetrahydrofuran, or tetrahydropyranyl;

R 4b is F, Cl, or —CH 3 ;

each R 4c is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(phenyl), —C(O)CH 2 (phenyl), —C(O)OCH 2 CH 3 , or C 3-6 cycloalkyl;

each R 5 is independently hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

each R x is independently hydrogen or —CH 3 ;

m is zero, 1, or 2;

n is zero, 1, or 2; and

q is 1 or 2.

2 . The compound according to claim 1 or stereoisomer, tautomer, solvate or salt thereof, wherein X is CR 3 .

3 . The compound according to claim 1 or stereoisomers, tautomer, solvates or salts thereof, wherein X is N.

4 . The compound according to claim 1 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is phenyl substituted —S(O) 2 CH 3 ;

A is cyclohexyl, piperidinyl, phenyl, or 6-azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 ;

L is a bond;

R 3 is hydrogen;

R 4 is piperidinyl, piperazinyl, azepanyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with R 4a ;

R 4a is —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —C(O)CH(CH 3 ) 2 , —C(O)(cyclopropyl), —CH 2 (cyclopropyl), —CH 2 (cyclobutyl), cyclopropyl, cyclobutyl, oxetanyl, or tetrahydropyranyl; and

each R 5 is hydrogen, F, or —CH 3 .

5 . The compound according to claim 1 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is

6 . The compound according to claim 1 or stereoisomer, tautomer, solvate or salt thereof, wherein said compound is:

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (7);

6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (8);

6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (9);

6-(1-(8-isopropyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (62-63);

7-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-5-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (66);

8-fluoro-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (67);

8-fluoro-6-(1-(8-isopropyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (68-69);

7-fluoro-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (70);

8-fluoro-6-(1-(1-isopropylazepan-4-yl)piperidin-4-yl)-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (71-72);

5-fluoro-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (73);

8-fluoro-7-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (74);

6-(1-(8-cyclobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (83-84);

6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (85-86);

6-(1-(8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (87-88);

6-(1-(8-(cyclobutylmethyl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (89-90);

6-(1′-cyclobutyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (91);

6-(1′-(cyclopropylmethyl)-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (92);

6-(1′-(cyclobutylmethyl)-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (93);

6-(4-(4-isobutylpiperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (99);

6-(4-(4-(cyclopropylmethyl) piperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (100);

6-(4-(4-(cyclobutylmethyl) piperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (101);

6-(4-(4-cyclobutylpiperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (102);

8-methyl-2-(4-(methylsulfonyl)phenyl)-6-(4-(4-(oxetan-3-yl) piperazin-1-yl) phenyl)imidazo[1,2-a]pyridine (103);

8-methyl-2-(4-(methylsulfonyl)phenyl)-6-(4-(4-(tetrahydro-2H-pyran-4-yl) piperazin-1-yl)phenyl)imidazo[1,2-a]pyridine (104);

6-(4-(4-(2-methoxyethyl) piperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (105);

7-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-5-methyl-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (106);

8-fluoro-6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (107);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (108);

6-(1′-(cyclopropylmethyl)-[1,4′-bipiperidin]-4-yl)-8-fluoro-2-(4-(methylsulfonyl) phenyl)imidazo[1,2-a]pyridine (109);

6-(1′-cyclobutyl-[1,4′-bipiperidin]-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (110);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-6-(1′-(oxetan-3-yl)-[1,4′-bipiperidin]-4-yl) imidazo[1,2-a]pyridine (111);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-6-(1′-(tetrahydro-2H-pyran-4-yl)-[1,4′-bipiperidin]-4-yl)imidazo[1,2-a]pyridine (112);

8-fluoro-6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (113-114);

6-(1-(8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (115-116);

6-(1-(8-cyclobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (117);

6-(1-(8-cyclobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (118);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-6-(1-(8-(oxetan-3-yl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)imidazo[1,2-a]pyridine (119-120);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-6-(1-(8-(tetrahydro-2H-pyran-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)imidazo[1,2-a]pyridine (121-122);

7-fluoro-6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (123);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-7-fluoro-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (124);

8-fluoro-6-(1-(1-isobutylazepan-4-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (125-126);

6-(1-(1-(cyclopropylmethyl) azepan-4-yl)piperidin-4-yl)-8-fluoro-2-(4-(methylsulfonyl)phenyl)imidazo[1,2-a]pyridine (127-128);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-6-(1-(1-(tetrahydro-2H-pyran-4-yl) azepan-4-yl)piperidin-4-yl)imidazo[1,2-a]pyridine (129-130);

5-fluoro-6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (131);

8-fluoro-7-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-2-(4-(methylsulfonyl)phenyl) imidazo[1,2-a]pyridine (132);

8-fluoro-2-(4-(methylsulfonyl)phenyl)-7-(1′-(tetrahydro-2H-pyran-4-yl)-[1,4′-bipiperidin]-4-yl)imidazo[1,2-a]pyridine (133);

6-(4-(4-isopropylpiperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (147);

6-(4-(8-isopropyl-3,8-diazabicyclo[3.2.1]octan-3-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (153);

6-(8-(1-cyclopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (159);

6-(8-(1-isopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (160);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (161);

6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (162);

6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (163); or

6-(4-(4-isopropylpiperazin-1-yl)phenyl)-2-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (167).

7 . A compound of Formula (III):

or stereoisomer tautomer, solvate or salt thereof, wherein:

X is N or CR 3 ;

one of Q 1 and Q 2 is A and the other of Q 1 and Q 2 is R 5 ;

G is phenyl substituted with 1 to 3 substituents independently selected from F, Cl, Br, C 1-2 alkoxy, C 1-2 fluoroalkoxy, C 3-4 cycloalkyl, —C(O)NR y R y , —S(O) 2 CH 3 , —S(O) 2 (phenyl), —S(O) 2 NR x R x , and —S(O) (NH) NR x R x ;

A is cyclohexyl, piperidinyl, phenyl, pyridinyl, pyrimidinyl, 6-azabicyclo[3.2.1]octanyl, or azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 and zero to 1 R 4b ;

L is a bond, —CR x R x — or —C(O)(CR x R x ) 0-2 —;

R 3 is hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

R 4 is:

(i) —N(CH 3 ) 2 ;

(ii) pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, pyridinyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with zero to 2 R 4a ; or

each R 4a is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —(CH 2 ) 0-2 O(C 1-2 alkyl), C 3-6 cycloalkyl, CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(C 3-6 cycloalkyl), —C(O)(phenyl), —C(O)CH 2 (C 3-6 cycloalkyl), —C(O)CH 2 (phenyl), —C(O)O(C 1-4 alkyl), oxetanyl, tetrahydrofuran, or tetrahydropyranyl;

R 4b is F, Cl, or —CH 3 ;

each R 4c is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(phenyl), —C(O)CH 2 (phenyl), —C(O)OCH 2 CH 3 , or C 3-6 cycloalkyl;

each R 5 is independently hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

each R x is independently hydrogen or —CH 3 ;

each R y is independently hydrogen or C 1-6 alkyl;

m is zero, 1, or 2;

n is zero, 1, or 2; and

q is 1 or 2.

8 . The compound according to claim 7 or stereoisomer, tautomer, solvate or salt, wherein X is CR 3 .

9 . The compound according to claim 7 or stereoisomer, tautomer, solvate or salt, wherein X is N.

10 . The compound according to claim 7 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is phenyl substituted with 1 to 2 substituents independently selected from F, —OCH 3 , and —S(O) 2 CH 3 ;

A is cyclohexyl, piperidinyl, phenyl, or 6-azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 ;

L is a bond;

R 3 is hydrogen;

R 4 is piperidinyl, piperazinyl, azepanyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with R 4a ;

R 4a is —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —C(O)CH(CH 3 ) 2 , —C(O)(cyclopropyl), CH 2 (cyclopropyl), CH 2 (cyclobutyl), cyclopropyl, cyclobutyl, oxetanyl, or tetrahydropyranyl; and

each R 5 is hydrogen, F, or —CH 3 .

11 . The compound according to claim 7 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is

12 . The compound according to claim 7 or stereoisomer, tautomer, solvate or salt thereof, wherein said compound is:

2-(3,4-dimethoxyphenyl)-6-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (31-33);

2-(3,4-dimethoxyphenyl)-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (34-36);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (37-38);

1-(4-(2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yl)-[1,4′-bipiperidin]-1′-yl)-2-methylpropan-1-one (39-41);

cyclopropyl(4-(2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yl)-[1,4′-bipiperidin]-1′-yl) methanone (42-44);

−(3,4-dimethoxyphenyl)-6-(1-(2-isopropyl-2-azaspiro[3.3] heptan-6-yl)piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (45-47);

6-(1-(2-cyclobutyl-2-azaspiro[3.3] heptan-6-yl)piperidin-4-yl)-2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (48-50);

6-(1-(2-(cyclopropylmethyl)-2-azaspiro[3.3] heptan-6-yl)piperidin-4-yl)-2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (51);

2-(3,4-dimethoxyphenyl)-6-(1-(2-isobutyl-2-azaspiro[3.3] heptan-6-yl)piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (52-54);

6-(1′-(cyclopropylmethyl)-[1,4′-bipiperidin]-4-yl)-2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (55-57);

2-(3,4-dimethoxyphenyl)-7-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (58);

2-(3,4-dimethoxyphenyl)-7-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (59);

(6R)-2-(3,4-dimethoxyphenyl)-6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl) piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (75-76);

(6S)-2-(3,4-dimethoxyphenyl)-6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl) piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (77-78);

(6R)-6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (79-80);

(6S)-6-(1-(8-isobutyl-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (81-82);

(6R)-2-(3,4-dimethoxyphenyl)-6-(1-(8-isopropyl-8-azabicyclo[3.2.1]octan-3-yl) piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (134-135);

(6S)-2-(3,4-dimethoxyphenyl)-6-(1-(8-isopropyl-8-azabicyclo[3.2.1]octan-3-yl) piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (136-137);

(6R)-6-(1-(8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (138-139);

(6S)-6-(1-(8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octan-3-yl)piperidin-4-yl)-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (140-141);

2-(3,4-dimethoxyphenyl)-6-(4-(4-isopropylpiperazin-1-yl) cyclohexyl)-8-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (143);

2-(3,4-dimethoxyphenyl)-6-(4-(4-isopropylpiperazin-1-yl)phenyl)-8-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (144);

6-(8-(1-cyclopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(3,4-dimethoxyphenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (145);

2-(3,4-dimethoxyphenyl)-6-(8-(1-isopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (148);

6-(4-(4-isopropylpiperazin-1-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (150);

2-(3,4-dimethoxyphenyl)-6-(4-(8-isopropyl-3,8-diazabicyclo[3.2.1]octan-3-yl) phenyl)-8-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (152); or

6-(4-(8-isopropyl-3,8-diazabicyclo[3.2.1]octan-3-yl)phenyl)-8-methyl-2-(4-(methylsulfonyl)phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (154).

13 . A compound of Formula (IIb):

or stereoisomer, tautomer, solvate or salt thereof, wherein:

one of Q 1 and Q 2 is A and the other of Q 1 and Q 2 is R 5 ;

G is phenyl substituted with 1 to 3 substituents independently selected from F, Cl, Br, C 1-2 alkoxy, C 1-2 fluoroalkoxy, C 3-4 cycloalkyl, or —C(O)NR y R y ;

A is cyclohexyl, piperidinyl, phenyl, pyridinyl, pyrimidinyl, 6-azabicyclo[3.2.1]octanyl, or azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 and zero to 1 R 4b ;

L is a bond, —CR x R x — or —C(O)(CR x R x ) 0-2 —;

R 3 is hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

R 4 is:

(i) —N(CH 3 ) 2 ;

(ii) pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, pyridinyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with zero to 2 R 4a ; or

each R 4a is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —(CH 2 ) 0-2 O(C 1-2 alkyl), C 3-6 cycloalkyl, —CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(C 3-6 cycloalkyl), —C(O)(phenyl), —C(O)CH 2 (C 3-6 cycloalkyl), —C(O)CH 2 (phenyl), —C(O)O(C 1-4 alkyl), oxetanyl, tetrahydrofuran, or tetrahydropyranyl;

R 4b is F, Cl, or —CH 3 ;

each R 4c is independently C 1-6 alkyl, C 1-3 fluoroalkyl, —CH 2 (C 3-6 cycloalkyl), —C(O)(C 1-4 alkyl), —C(O)(phenyl), —C(O)CH 2 (phenyl), —C(O)OCH 2 CH 3 , or C 3-6 cycloalkyl;

each R 5 is independently hydrogen, F, Cl, C 1-3 alkyl, C 1-2 fluoroalkyl, or C 3-4 cycloalkyl;

each R x is independently hydrogen or —CH 3 ;

m is zero, 1, or 2;

n is zero, 1, or 2; and

q is 1 or 2.

14 . The compound according to claim 13 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is phenyl substituted with 1 to 2 substituents independently selected from F or —OCH 3 ;

A is cyclohexyl, piperidinyl, phenyl, or 6-azabicyclo[3.2.1]octanyl, each substituted with -L-R 4 ;

L is a bond;

R 3 is hydrogen;

R 4 is piperidinyl, piperazinyl, azepanyl, azaspiro[3.3]heptanyl, azabicyclo[3.2.1]octanyl, or diazabicyclo[3.2.1]octanyl, each substituted with R 4a ;

R 4a is —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —C(O)CH(CH 3 ) 2 , —C(O)(cyclopropyl), CH 2 (cyclopropyl), CH 2 (cyclobutyl), cyclopropyl, cyclobutyl, oxetanyl, or tetrahydropyranyl; and

each R 5 is hydrogen, F, or —CH 3 .

15 . The compound according to claim 14 or stereoisomer, tautomer, solvate or salt thereof, wherein:

G is

16 . The compound according to claim 14 or stereoisomer, tautomer, solvate or salt thereof, wherein said compound is:

2-(3,4-dimethoxyphenyl)-7-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-[1,2,4]triazolo[1,5-a] pyridine (60);

2-(3,4-dimethoxyphenyl)-7-(1′-isobutyl-[1,4′-bipiperidin]-4-yl)-[1,2,4]triazolo[1,5-a] pyridine (61);

2-(3,4-dimethoxyphenyl)-6-(4-(4-isopropylpiperazin-1-yl)phenyl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (142);

6-(8-(1-cyclopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(3,4-dimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (146);

2-(3,4-dimethoxyphenyl)-6-(8-(1-isopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-y1)-[1,2,4]triazolo[1,5-a]pyridine (149);

2-(3,4-dimethoxyphenyl)-6-(4-(8-isopropyl-3,8-diazabicyclo[3.2.1]octan-3-yl)phenyl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (151);

6-(8-(1-cyclopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(3,4-dimethoxyphenyl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (155);

2-(3,4-dimethoxyphenyl)-6-(8-(1-isopropylpiperidin-4-yl)-8-azabicyclo[3.2.1]octan-3-y1)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (156);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-2-(3,4-dimethoxyphenyl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (157);

2-(3,4-dimethoxyphenyl)-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (158);

6-(1′-cyclopropyl-[1,4′-bipiperidin]-4-yl)-2-(3,4-dimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (164);

2-(3,4-dimethoxyphenyl)-6-(1′-isopropyl-[1,4′-bipiperidin]-4-yl)-[1,2,4]triazolo[1,5-a] pyridine (165); or

2-(3,4-dimethoxyphenyl)-6-(4-(8-isopropyl-8-azabicyclo[3.2.1]octan-3-yl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (166).

17 . A pharmaceutical composition comprising a compound according to claim 1 or stereoisomer, tautomer, solvate or salt thereof; and a pharmaceutically acceptable carrier.

18 . A pharmaceutical composition comprising a compound according to claim 7 or stereoisomer, tautomer, solvate or salt thereof; and a pharmaceutically acceptable carrier.

19 . A pharmaceutical composition comprising a compound according to claim 13 or stereoisomer, tautomer, solvate or salt thereof; and a pharmaceutically acceptable carrier.

Continuity (2)

References Cited (54)