Alpha-hydroxy amides as bradykinin antagonists or inverse agonists

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof

wherein

Y is N;

R 1 is

R 2a is selected from (1) a group selected from R a , (2) (CH 2 ) n NR b C(O)R a , (3) (CH 2 ) n NR b SO 2 R d , (4) (CH 2 ) n NR b CO 2 R a , (5) (CH 2 ) k CO 2 R a , and (6) (CH 2 ) k C(O)NR b R c ,

R 2b is OH or a group selected from R 2a ; or

R 2a and R 2b together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted with 1 to 4 groups independently selected from halogen, OR a , C 1-4 alkyl and C 1-4 haloalkyl;

R 3a and R 3b are independently selected from hydrogen, C 1-4 alkyl, and C 1-4 haloalkyl;

R 6 is optionally substituted 1,2,4-oxadiazolyl, and wherein said substituent is 1 to 3 groups independently selected from C 1-4 alkyl optionally substituted with 1 to 5 halogen atoms, OR a or OC(O)R a ;

R 7 is selected from hydrogen and halogen;

R 8 and R 9 are independently selected from (1) hydrogen, (2) C 1-8 alkyl optionally substituted with 1-5 groups independently selected from halogen, nitro, cyano, COR a , CO 2 R a , C(O)NR b R c , OR a , OC(O)R a , SR a , SO 2 R d , S(O)R d , NR b R c , NR b C(O)R a , NR b SO 2 R d , and NR b CO 2 R a , (3) C 3-8 cycloalkyl, (4) C 2-8 alkenyl optionally substituted with CO 2 R a , (5) halogen, (6) cyano, (7) nitro, (8) NR b R c , (9) NR b C(O)R a , (10) NR b CO 2 R a , (11) NR b C(O)NR b R c , (12) NR b C(O)NR b CO 2 R a , (13) NR b SO 2 R d , (14) CO 2 R a , (15) COR a , (16) C(O)NR b R c , (17) C(O)NHOR a , (18) C(═NOR a )R a , (19) C(═NOR a )NR b R c , (20) OR a , (21) OC(O)R a , (22) S(O) v R d , (23) SO 2 NR b R c , and (24) phenyl optionally substituted with 1 to 3 groups independently selected from halogen, nitro, cyano, OR a , SR a , C 1-4 alkyl and C 1-4 haloalkyl, and (25) OSO 2 R d ;

R a is selected from (1) hydrogen, (2) C 1-7 alkyl optionally substituted with 1 to 5 halogen atoms, OH, SH, O—C 1-4 alkyl, or S—C 1-4 alkyl, (3) (CH 2 ) k -phenyl optionally substituted with 1 to 3 groups independently selected from halogen, cyano, nitro, OH, C 1-4 alkyloxy, C 3-6 cycloalkyl, C 1-4 alkyl and C 1-4 haloalkyl, and (4) C 3-6 cycloalkyl;

R b and R c are independently selected from (1) hydrogen, (2) C 1-4 alkyl optionally substituted with 1 to 5 groups independently selected from halogen, amino, CO 2 R a , OR a , mono-C 1-4 alkylamino, and di-C 1-4 alkylamino, (3) (CH 2 ) k -phenyl optionally substituted with 1 to 3 groups selected from halogen, cyano, nitro, OR a , CO 2 R a , C 3-6 cycloalkyl, C 1-4 alkyl and C 1-4 haloalkyl, and (4) C 3-6 cycloalkyl;

R d is selected from (1) C 1-4 alkyl, (2) C 1-4 haloalkyl, (3) C 1-4 alkyloxy, and (4) (CH 2 ) k -phenyl optionally substituted with 1 to 3 groups selected from halogen, cyano, nitro, OR a , CO 2 R a , C 3-6 cycloalkyl, C 1-4 alkyl and C 1-4 haloalkyl;

R e is selected from hydrogen, C 1-4 alkyl, C 1-4 haloalkyl, C(O)H and C(O)C 1-4 alkyl;

n is 1, 2, or 3;

k is 0, 1, 2, 3, or 4; and

v is 0, 1, or 2.

2. A compound of claim 1 wherein R 2a , R 2b and the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted with 1 to 4 groups independently selected from halogen, OR a , C 1-4 alkyl and C 1-4 haloalkyl.

3. A compound of claim 1 wherein R 8 is hydrogen or 3-halo, and R 9 is hydrogen or 5-halo.

4. A compound of claim 1 having the formula (Ia) or a pharmaceutically acceptable salt thereof:

wherein m is 1 to 5; Y is N; one of R 3a and R 3b is hydrogen and the other is hydrogen or methyl; R 7 is hydrogen or fluorine; R 6 is 1,2,4-oxadiazolyl; and R 8 and R 9 are independently hydrogen or halogen.

5. A compound of claim 1 having the formula Ib or a pharmaceutically acceptable salt thereof:

where R 3a , R 3b , R 6 , R 7 , R 8 and R 9 are as defined in claim 1 , and R 2a′ and R 2b′ are independently selected from (1) hydrogen, (2) C 1-7 alkyl optionally substituted with 1 to 5 halogen atoms, SH, OH, S—C 1-4 alkyl or OC 1-4 alkyl, (3) (CH 2 ) k -phenyl optionally substituted with 1 to 3 groups independently selected from halogen, cyano, nitro, OH, C 1-4 alkyloxy, C 3-6 cycloalkyl, C 1-4 alkyl and C 1-4 haloalkyl, and (4) C 3-6 cycloalkyl.

6. A compound of claim 5 wherein R 2a′ and R 2b′ are independently C 1-7 alkyl optionally substituted with 1 to 5 halogen atoms.

7. A compound of claim 6 wherein one of R 3a and R 3b is hydrogen and the other is hydrogen or methyl; R 7 is hydrogen, chlorine or fluorine; and R 8 and R 9 are independently hydrogen or halogen.

8. A compound of claim 1 having the formula Ic or a pharmaceutically acceptable salt thereof:

wherein Y is N; R 7 is H, chlorine or fluorine; R 3a is H or methyl; R 6 is 1,2,4-isoxazolyl optionally substituted with a C 1-4 alkyl group; and R 8 and R 9 are independently hydrogen or halogen.

9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

10. A compound of claim 1 being (2R)—N-((1R)-1-{5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide or a pharmaceutically acceptable salt thereof.