Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use

1. A compound represented by formula I:

or a pharmaceutically acceptable salt thereof wherein:

ring A represents a quinolinyl group;

each R 1 represents H or is selected from the group consisting of halo, CN, OH, NO 2 , CO 2 R a , NR a R b , S(O) p R a , C 1-10 alkyl, C 2-10 alkenyl or C 1-10 alkoxy, the alkyl and alkenyl portions of C 1-10 alkyl, C 2-10 alkenyl and C 1-10 alkoxy being optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substituted with 1 group selected from OH, oxo and C 1-6 alkoxy;

p represents 0, 1 or 2;

each R a and R b independently represents H or C 1-4 alkyl optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substituted with 1 group selected from OH, oxo and C 1-6 alkoxy;

R 2 represents C 1-6 alkyl, optionally substituted with 1-5 halo atoms up to perhalo, and

each R 3 represents H or is selected from the group consisting of halo, CN, C 1-10 alkyl, and C 1-10 alkoxy, the alkyl portions of C 1-10 alkyl and C 1-10 alkoxy being optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substituted with 1 group selected from NR a R b , and C 1-6 alkoxy;

or 3 R 3 groups are as described above and 1 R 3 represents a 5-6 membered heteroaryl ring containing 0-1 oxygen or sulfur atom and 1-4 nitrogen atoms, said heteroaryl group being optionally substituted with 1-2 halo, C 1-3 alkyl, or C 1-3 alkoxy groups, the alkyl and portions of C 1-3 alkyl, and C 1-3 alkoxy being optionally substituted with 1-3 halo atoms up to perhalo.

2. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 1 represents H or is selected from the group consisting of halo selected from fluoro and chloro, SCH 3 , CN, C 1-6 alkyl, C 2-4 alkenyl and C 1-6 alkoxy, the alkyl and alkenyl portions of SCH 3 , C 1-6 alkyl, C 2-4 alkenyl and C 1-6 alkoxy being optionally substituted with 1-3 fluoro atoms.

3. A compound in accordance with claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R 1 represents H or is selected from the group consisting of: fluoro, chloro, SCH 3 , CH 2 , OCH 3 , CF 3 , and OCF 3 .

4. A compound in accordance with claim 3 , or a pharmaceutically acceptable salt thereof, wherein each R 1 represents H or is selected from the group consisting or: 3-fluoro, 4-fluoro, 5-fluoro, 3-chloro, 4-chloro, 5-chloro, 4-methyl, 4-methoxy, 4-CF 3 and 4-OCF 3 .

5. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R represents a member selected from the group consisting of: CH 3 , ethyl n-prooyl, isopropyl, n-, s- and t-butyl, isobutyl, neopentyl, and allyl, all optionally substituted with 1-3 fluoro atoms.

6. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 2 represents a member selected from the group consisting of: ethyl, n-propyl and —CH 2 CH 2 CF 3 .

7. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein each R 3 represents H or is selected from the group consisting of halo, CN, C 1-10 alkyl or C 1-10 alkoxy, the alkyl portions of, C 1-10 alkyl and C 1-10 alkoxy being optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substituted with C 1-6 alkoxy.

8. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof, wherein three R groups represent H or halo, and one R 3 group represents a 5-6 membered heteroaryl ring containing 0-1 oxygen or sulfur atom and 1-4 nitrogen atoms, said heteroaryl group being optionally substituted with 1-2 halo, C 1-3 alkyl or C 1-3 alkoxy groups, the alkyl portions of, C 1-3 alkyl and C 1-3 alkoxy being optionally substituted with 1-3 halo atoms up to perhalo.

9. A compound in accordance with claim 7 or a pharmaceutically acceptable salt thereof wherein each R 3 represents H or is selected from the group consisting of fluoro, chloro; CN, C 1-10 alkyl and C 1-10 alkoxy, the alkyl portions of C 1-10 alkyl and C 1-10 alkoxy being optionally substituted with 1-3 fluoro atoms.

10. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein each R 3 represents H or is selected from the group consisting of: fluoro, chloro, methyl, ethyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, isobutyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy methoxyethoxy, dimethylaminoethoxy cyano, trifluoromethyl, trifluoromethoxy, difluoromethoxy.

11. A compound in accordance with claim 1 or a pharmaceutically acceptable sail thereof wherein one R 3 represents a 5-6 membered heteroaryl ring containing 0-1 oxygen or sulfur atom and 1-4 nitrogen atoms.

12. A, compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of; H, Me, Et, n-propyl and n-butyl.

13. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein:

ring A represents a quinolinyl group,

each R 1 represents H or is selected from the group consisting or halo selected from fluoro and chloro: SCH 3 ; CN, C 1-6 alkyl, C 2-4 alkenyl and C 1-6 alkoxy,

the alkyl and alkenyl portions of SCH 3 , C 1-6 alkyl, C 2-4 alkenyl and C 1-6 alkoxy being optionally substituted with 1-3 fluoro atoms,

R 2 represents a member selected from the group consisting of: CH 3 , ethyl, n-propyl, isopropyl, n-, s- and t-butyl, isobutyl neopentyl, and allyl, all optionally substituted with 1-3 fluoro atoms;

each R 3 represents H or is selected from the group consisting of halo, CN, C 1-10 alkyl or C 1-10 alkoxy, the alkyl portions of, C 1-10 alkyl, and C 1-10 alkoxy being optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substitued with C 1-6 alkoxy;

p represents 0, 1 or 2; and

each R a and R b independently represents H or C 1-4 alkyl optionally substituted with 1-5 halo atoms up to perhalo; and further optionally substituted with 1 group selected from OH, oxo and C 1-6 alkoxy.

14. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein 1 R 3 is selected from the group consisting of: pyrrolo, pyrazole, isoxazolo and dimethylisoxazolo.

15. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein the compound is individually selected from the following tables compounds:

TABLE 1-A

EXAMPLE 1

EXAMPLE 2

EXAMPLE 3

EXAMPLE 157

EXAMPLE 169

EXAMPLE 170

EXAMPLE 171

EXAMPLE 172

and

EXAMPLE 185

or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.

17. A method of treating type 2 diabetes mellitus in a mammalian patient in need of such treatment comprising administering to said patient a compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof in an amount that is effective to treat said type 2 diabetes mellitus.