Quinolinyl glucagon receptor modulators

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein

R 1 is (C 1 -C 6 )alkyl which is optionally substituted with one to three fluoro, hydroxy or methoxy; (C 3 -C 7 )cycloalkyl which is optionally substituted with one to two fluoro or one to two (C 1 -C 3 )alkyl which are each optionally substituted with one to three fluoro and wherein one carbon of the (C 3 -C 7 )cycloalkyl can be replaced with an O; or (C 3 -C 7 )cycloalkyl-(C 1 -C 6 )alkyl wherein the (C 3 -C 7 )cycloalkyl group of said (C 3 -C 7 )cycloalkyl-(C 1 -C 6 )alkyl is optionally substituted with one to two (C 1 -C 3 )alkyl which are each optionally substituted with one to three fluoro;

R 2 is hydrogen or (C 1 -C 3 )alkyl;

R 3 is tetrazolyl, —CH 2 -tetrazolyl, —(CH 2 ) 2 SO 3 H, —(CH 2 ) 2 CO 2 H, —CH 2 CHFCO 2 H or —CH 2 CH(OH)CO 2 H;

One of A 1 , A 2 and A 3 is N and the remaining two of A 1 , A 2 and A 3 are CR 4 ;

R 4 at each occurrence is independently hydrogen, halo, cyano, (C 1 -C 3 )alkyl optionally substituted with one to three fluoro, (C 1 -C 3 )alkoxy optionally substituted with one to three fluoro, or (C 3 -C 5 )cycloalkyl;

B 1 , B 2 , B 3 and B 4 are each independently CR 5 ; and

R 5 at each occurrence is independently hydrogen, halo, cyano, (C 1 -C 3 )alkyl optionally substituted with one to three fluoro, or (C 1 -C 3 )alkoxy optionally substituted with one to three fluoro, or (C 3 -C 5 )cycloalkyl.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen and R 3 is —(CH 2 ) 2 CO 2 H.

3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is ethyl, propyl, isopropyl, isobutyl, t-butyl, pentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl each optionally substituted with 1 to 3 fluoro and wherein said cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl are each optionally substituted with 1 to 2 methyl.

4. The compound according to claim 3 , or a pharmaceutically acceptable salt thereof, wherein

A 1 and A 2 are each CR 4 and A 3 is N;

R 4 at each occurrence is independently hydrogen, fluoro, chloro, methyl or ethyl; and

R 5 at each occurrence is independently hydrogen, fluoro, chloro, methyl, trifluoromethyl or methoxy.

5. The compound according to claim 1 selected from the group consisting of

(+/−)-3-(4-(1-(3-methylquinolin-2-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-{4-[3-methyl-1-(quinolin-3-ylamino)-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[3-methyl-1-(quinolin-2-ylamino)-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[1-(8-methoxy-quinolin-2-ylamino)-3-methyl-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[3-methyl-1-(4-methyl-quinolin-2-ylamino)-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[3-methyl-1-(3-methyl-quinolin-2-ylamino)-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[1-(7-fluoro-4-methyl-quinolin-2-ylamino)-3-methyl-butyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[1-(8-chloro-quinolin-2-ylamino)-3-methyl-butyl]-benzoylamino}-propionic acid;

(+/−)3-(4-(3-methyl-1-(7-(trifluoromethyl)quinolin-2-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-(4-(3-methyl-1-(6-(trifluoromethyl)quinolin-2-ylamino)butyl)benzamido)propanoic acid;

(+\−)-3-(4-(3-methyl-1-(2-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid;

(+\−)-3-(4-(3-methyl-1-(4-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(6-fluoro-3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid;

(+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(7-fluoro-3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid;

(+/−)3-(4-((3,3-dimethylcyclobutyl)(6-fluoroquinolin-3-ylamino)methyl)benzamido)propanoic acid;

(+/−)-3-(4-((3,3-di methylcyclobutyl)(7-fluoroquinolin-3-ylamino)methyl)benzamido)propanoic acid;

(+/−)-3-(4-(4,4,4-trifluoro-1-(quinolin-3-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-(4-((6,7-difluoroquinolin-3-ylamino)(3,3-dimethylcyclobutyl)methyl)benzamido)propanoic acid;

(+/−)-3-(4-(3-methyl-1-(7-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-(4-(3-methyl-1-(8-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid;

(+/−)-3-(4-(3-methyl-1-(6-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid; and

(+/−)-3-(4-(3-methyl-1-(5-methylquinolin-3-ylamino)butyl)benzamido)propanoic acid;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 selected from the group consisting of

(+)-3-(4-(1-(3-methylquinolin-2-ylamino)butyl)benzamido)propanoic acid;

(−)-3-(4-(1-(3-methylquinolin-2-ylamino)butyl)benzamido)propanoic acid;

(+)-3-(4-(3-methyl-1-(3-methylquinolin-2-ylamino)butyl)benzamido)propanoic acid; and

(−)-3-(4-(3-methyl-1-(3-methylquinolin-2-ylamino)butyl)benzamido)propanoic acid;

or a pharmaceutically acceptable salt thereof.

7. (R)3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid or a pharmaceutically acceptable salt thereof.

8. (S)3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid or a pharmaceutically acceptable salt thereof.

9. (R)3-{4-[(3,3-dimethyl-cyclobutyl)-(6-fluoro-3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid or a pharmaceutically acceptable salt thereof.

10. (S)3-{4-[(3,3-dimethyl-cyclobutyl)-(6-fluoro-3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising (i) a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and (ii) a pharmaceutically acceptable excipient, diluent, or carrier.

12. A method for treating obesity in a human comprising administering to the human in need of such treatment a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

13. A method for treating or delaying the progression or onset of type 2 diabetes in a human comprising administering to the human in need of such treatment a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.