Heterocycle phenyl amide T-type calcium channel antagonists

1. A compound of the formula Id:

wherein:

A is selected from the group consisting of:

(1) benzimidazolyl,

(2) benzofuranyl,

(3) dihydroisoxazolyl,

(4) dihydropyrrolopyrrolyl,

(5) furopyridinyl,

(6) furopyrrolyl,

(7) imidazopyrazinyl,

(8) imidazopyridazinyl,

(9) imidazopyridinyl,

(10) imidazopyrimidinyl,

(11) indazolyl,

(12) indolizinyl;

(13) indolyl,

(14) isoindolyl,

(15) isoquinolinyl,

(16) naphthyrindinyl,

(17) oxotriazolopyridinyl,

(18) pyrazinyl,

(19) pyrazolopyrazinyl,

(20) pyrazolopyridazinyl,

(21) pyrazolopyrimidinyl,

(22) pyridazinyl,

(23) pyridinyl,

(24) pyridopyrazinyl,

(25) pyridopyridazinyl,

(26) pyridopyrimidinyl,

(27) pyrrolooxazolyl,

(28) pyrrolopyridinyl,

(29) pyrrolopyrimidinyl,

(30) quinazolinyl,

(31) quinolinyl,

(32) quinoxalinyl,

(33) tetrahydrofuranyl,

(34) thiazolyl,

(35) triazolopyrazinyl,

(36) triazolopyridazinyl,

(37) triazolopyridinyl, and

(38) triazolopyrimidinyl;

R 1a , R 1b and R 1c are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) phenyl or napthyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O-C 1-6 alkyl, C 3-6 cycloalkyl, —SH, —S-C 1-6 alkyl, —NO 2 ,—CO 2 H, or —CN,

(4) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O-C 1-6 alkyl, —SH, —S-C 1-6 alkyl, —NO 2 , —CO 2 H, or —CN,

(5) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or —O-C 1-6 alkyl,

(6) C 3-6 cycloalkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or —O-C 1-6 alkyl,

(7) C2 — 4alkenyl, which is unsubstituted or substituted with C 3-6 cycloalkyl or phenyl,

(8) —NR 10 R 11 , wherein R 10 and R 11 are independently selected from hydrogen and C 1-6 alkyl,

(9) isoxazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(10) imidazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(11) morpholinyl, which is unsubstituted or substituted with C 1-6 alkyl,

(12) oxazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(13) pyrazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(14) pyrrolidinyl, which is unsubstituted or substituted with halogen,

(15) tetrazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(16) thienyl, which is unsubstituted or substituted with C 1-6 alkyl,

(17) benzothienyl, which is unsubstituted or substituted with C 1-6 alkyl,

(18) triazolyl, which is unsubstituted or substituted with C 1-6 alkyl,

(19) —NO 2 ,and

(20) —CN,

or R 1a and R 1b taken together form a cyclopentyl, cyclohexyl, dihydrofuranyl or dihydropyranyl ring, which is unsubstituted or substituted with —CH 3 , (═CH 2 ). keto, or hydroxyl;

R 4 is selected from the group consisting of:

(1) CH 3 ,

(2) CH 2 OH,

(3) CH 2 OCH 3 ,

(4) CH 2 CH 3 ,

(5) CH═CH 2 ,

(6) CH 2 CH 2 OH,

(7) CH 2 CH═CH 2 ,

(8) CH 2 CH 2 F,

(9) CH 2 CF 2 ,

(10) CH 2 -phenyl,

(12) CH 2 -cyclopropyl,

(13) CH 2 -cyclobutyl,

(14) cyclopropyl,

(15) cyclobutyl,

(16) CH 2 CH 2 CH 3 , and

(17) —(C═O)—O—CH 3 ;

R 5a is independently selected from the group consisting of:

(1) hydrogen,

(2) fluoro,

(3) chloro,

(4) bromo,

(5) hydroxyl,

(6) —CH 3 ,

(7) —CH 2 OH,

(8) —CH 2 CH 3 ,

(9) —CH 2 ═CH 2 ,

(10) —CH 2 CH 2 CH 3 ,

(11) -cyclopropyl

(12) —OCH 3 ,

(13) —OCH 2 F,

(14) —OCH 2 -cyclopropyl,

(15) —OCH 2 -phenyl,

(16) —OCH 2 CH 3 ,

(17) —OCH 2 CF 3 ,

(18) —OCH 2 CH 2 CH 3 ,

(19) —OCH 2 (C═O)OCH 2 CH 3 , and

(20) —OCH 2 (C═O)NHCH 2 CH 3 ;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein R 4 is in the (R) orientation.

3. The compound of claim 1 wherein R 4 is CH 3 .

4. A compound which is selected from the group consisting of:

2-(4-quinazolin-8-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-[4-(3-methylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(1-methyl-1H-indo-2-yl)phenyl]-N-{(1R)-1 -[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-(4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-(4-pyrazin-2-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-[4-(3-cyclopropylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoro ethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(3,5-dimethyl-4,5-dihydro-isoxazol-5-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy) pyridin-2-yl]ethyl}acetamide;

2-[4-(tetrahydrofuran-3-yloxy)phenyl]-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl }ethyl)acetamide;

2-[4-(1,3-thiazol-2-yloxy)phenyl]-N-((1R)-1-{5 -[(2,2,2-trifluoroethyl)amino]pyridin-2-yl }ethyl)acetamide;

2-[4-(3-cyclopropyl-1H-indazole-1-yl)phenyl]-N-((1R)- 1-{5-[(2,2,2-trifluoroethyl) amino]pyridin-2-yl}ethyl)acetamide;

2-[4-(1H-indazol-4-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(1H-pyrrolo [2,3 -b]pyridin-4-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(2-cyclopropyl-1H-benzimidazol-1-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-[4-(1,3-thiazol-2-yloxy)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(1H-pyrrolo [2,3-b]pyridin-1-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(3-cyclopropyl-1H-indazol-1-yl)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(3-oxo [1,2,4]triazolo [4,3-a]pyridin-2(3H)-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy) pyridin-2-yl]ethyl}acetamide;

2-[4-(tetrahydrofuran-3-yloxy)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoro ethoxy)pyridin-2-yl ]ethyl}acetamide;

2-(4-pyrazolo [1,5-b]pyridazin-3-ylphenyl)-N-{(1R)-1 -[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(1H-indazol-1-yl)phenyl]-N-{(1R)-1-[5 -(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}-2-(4-{[4-(trifluoromethyl)pyridin-2-yl ]oxy}phenyl)acetamide;

2-[4-(pyridin-2-yloxy)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-[4-(3-cyclopropylpyrazin-2-yl)phenyl]-N-{(1R)-1 [5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2-[4-(4,5-dihydroisoxazol-5-yl)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

2- [4-(3,5-dimethyl-4,5-dihydroisoxazol-5-yl)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy) pyridin-2-yl]ethyl}acetamide;

2-(4-pyrazin-2-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-(4-isoquinolin-4-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-(4-quinazolin-5-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-(4-quinazolin-8-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-(4-quinazolin-4-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-(4-quinoxalin-5-ylphenyl)-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide;

2-[4-(1,5-naphthyridin-4-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide; and

2-[4-(1-methyl-1H-indo2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl ]ethyl}acetamide;

or a pharmaceutically acceptable salt thereof.

5. A compound which is 2-[4-(3-methylpyrazin-2-yl) phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 which is 2[4(3-methylpyrazin -2-yl)phenyl]-N-{(1R)-1[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide.

7. The compound of claim 5 which is 2-[4-(3-methylpyrazin -2-yl)phenyl]-N-{(1R)-1-[5(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide in the form of a pharmaceutically acceptable salt.

8. A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition which comprises an inert carrier and a compound of claim 4 or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition which comprises an inert carrier and a compound of claim 5 or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition which comprises an inert carrier and a compound of claim 6 or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition which comprises an inert carrier and a compound of claim 7 or a pharmaceutically acceptable salt thereof.