Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators
View Patent ↗A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.
1. A compound having structural Formula I:
or a pharmaceutically acceptable salt thereof wherein:
C* is indicates a potential chiral carbon atom;
R 1 is
(1) hydrogen
(2) (C 1-6 )alkyl,
(3) halo(C 1-6 )alkyl,
(4) (C 1-6 )alkyl-O—,
(5) halo(C 1-6 )alkyl-O—,
(6) (C 3-7 )cycloalkyl-(C 1-3 )alkyl-O—,
(7) —(C 1-3 )alkyl-(C 3-7 )cycloalkyl, or
(8) —(C 1-3 )alkyl-phenyl, wherein phenyl is unsubstituted or substituted by 1 to 3 halo;
R 2 is
(1) (C 1-3 )alkyl, or
(2) (C 3-7 )cycloalkyl;
R 3 is
(1) phenyl unsubstituted or substituted by 1 to 3 R 7 , or
(2) five- or six-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O and S, wherein heteroaryl is unsubstituted or substituted by 1 to 3 R 7
(3) —C(O)NH—(C 3-6 )cycloalkyl,
(4) (C 1-6 )alkyl, or
(5) —CO 2 -(C 1-6 )alkyl;
R 4 is
(1) hydrogen,
(2) (C 1-6 )alkyl,
(3) halo(C 1-6 )alkyl,
(4) (C 1-6 )alkoxy,
(5) halo(C 1-3 )alkoxy,
(6) (C 3-7 )cycloalkyl, or
(7) cyano;
R 5 is
(1) hydrogen,
(2) (C 1-6 )alkyl,
(3) halo(C 1-6 )alkyl,
(4) halo,
(5) amino,
(6) (C 1-3 )alkyl-aryl,
(7) (C 1-3 )alkyl-(C 3-6 )cycloalkyl, or
(8) cyano;
R 6 is
(1) hydrogen,
(2) hydroxy,
(3) (C 1-6 )alkyl,
(4) (C 1-6 )alkoxy,
(5) (C 1-3 )alkyl-O—(C 1-3 )alkoxy-
(6) (C 3-6 )cycloalkyl,
(7) cyano,
(8) phenyl, or
(9) —C(O)NH 2 ; and
each R 7 is independently
(1) (C 1-3 )alkoxy,
(2) halo(C 1-3 )alkoxy,
(3) halo,
(4) —CO 2 -(C 1-6 )alkyl, or
(5) C(O)NH 2 .
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein: R 3 is an phenyl unsubstituted or substituted by 1 to 3 R 7 or a six-membered heteroaryl containing 1 or 2 N heteroatoms, wherein heteroaryl is unsubstituted or substituted by 1 to 3 R 7 .
3. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein: R 3 is
4. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 is —C(O)NH—(C 3-6 )cycloalkyl.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein: R 3 is (C 1-6 )alkyl.
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein: R 6 is hydrogen, hydroxy, methyl, ethyl, cyano, cyclopropyl, phenyl, methoxy, 2-methoxyethoxy, or —C(O)NH 2 .
7. The compound of claim 6 or a pharmaceutically acceptable salt thereof wherein R 6 is hydrogen or hydroxy.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein: R 1 is (C 1-6 )alkyl, halo(C 1-6 )alkyl, —(C 1-3 )alkyl-phenyl, or —(C 1-3 )alkyl-(C 3-7 )cycloalkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein: R 1 is (C 1-6 )alkyl-O—, halo(C 1-6 )alkyl-O—, or (C 3-7 )cycloalkyl-(C 1-3 )alkyl-O—.
10. The compound of claim 8 , or a pharmaceutically acceptable salt thereof wherein: R 2 is methyl or cyclopropyl.
11. The compound of claim 1 , which is:
5-(4-Fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-c]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(4-fluorobenzyl)imidazo[1,2-c]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(4-fluorobenzyl)imidazo[1,2-c]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-cyclopropyl-4-hydroxy-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-c]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(4-fluorophenyl)-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(4-fluorophenyl)-4-hydroxy-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-propylimidazo[1,2-c]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-propylimidazo[1,2-c]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-2-(8-(4-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-cyclopropyl-5-(3,4-difluorophenyl)-4-hydroxy-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(3,4-difluorophenyl)-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chloro-3-fluorophenyl)-5-cyclopropyl-4-hydroxy-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chlorophenyl)-5-cyclopropyl-4-hydroxy-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-5-cyclopropyl-4-hydroxy-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chloro-2-fluorophenyl)-5-cyclopropyl-4-hydroxy-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-2-fluorophenyl)-5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(4-fluorophenyl)-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-Chloropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(3,4-difluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-5-methyl-2-(8-propylimidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-methyl-2-(8-propylimidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-2-(8-isobutylimidazo[1,2-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-2-(8-(4-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-cyclopropyl-5-(3,4-difluorophenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(3,4-difluorophenyl)-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chloro-2-fluorophenyl)-5-cyclopropyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-2-fluorophenyl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chloro-3-fluorophenyl)-5-cyclopropyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-chlorophenyl)-5-cyclopropyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-cyclopropyl-5-(4-(trifluoromethoxy)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5-(4-(trifluoromethoxy)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(5-fluoropyridin-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(5-fluoropyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-5-cyclopropyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chloro-3-fluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-methyl-2-(8-propylimidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-chloropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-cyclopropyl-5-(4-fluorophenyl)-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-fluorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(cyclobutylmethyl)imidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
N,5-dicyclopropyl-2-(8-(4-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,
N-cyclopropyl-2-(8-(2-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,
N,5-dicyclopropyl-2-(8-(2-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide,
4-Cyclopropyl-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-4-cyclopropyl-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
4-cyclopropyl-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-chlorophenyl)-4-cyclopropyl-5-methyl-2-(8-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
4-cyclopropyl-5-(4-fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
4-ethyl-5-(4-fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-fluorophenyl)-4,5-dimethyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-Butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-Butylimidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(4-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(4-fluorobenzyl)imidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-butylimidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Chlorophenyl)-2-(imidazo[1,2-a]pyrazin-6-yl)-5-methyl-4-phenyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Fluorophenyl)-5-methyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-4-carbonitrile,
5-(4-Fluorophenyl)-5-methyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-4-carboxamide,
2-(3-Amino-8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Fluorophenyl)-4-(2-methoxyethoxy)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Fluorophenyl)-4-methoxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)imidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-Butyl-2-methylimidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-Butyl-2-methylimidazo[1,2-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Fluorophenyl)-5-methyl-2-(8-propoxyimidazo[1,2-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
2-(8-(2-Cyclopropylethoxy)imidazo[1,2-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
5-(4-Chlorophenyl)-2-(8-(2-cyclopropylethoxy)imidazo[1,2-a]pyrazin-6-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one, or
2-(8-Benzylimidazo[1,2-a]pyrazin-6-yl)-5-isopropyl-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,
or a pharmaceutically acceptable salt thereof.
12. A method for activating soluble guanylate cyclase comprising the step of administering an amount efficacious therefor of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof.
13. A method for the treatment of one or more conditions selected from cardiovascular disease, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary hypertension, angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney disease, diabetes or cirrhosis of the liver comprising administering a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.
14. A method for the treatment of hypertension comprising administering a therapeutically effective amount of the compound of any one of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.
15. A method for the treatment of heart failure comprising administering a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.
16. A pharmaceutical composition comprising of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , further comprising one or more additional active agents.
18. The pharmaceutical composition of claim 17 wherein the one or more additional active agents is selected from an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a neutral endopeptidase inhibitor, an aldosterone antagonist, a renin inhibitor, an endothelin receptor antagonist, an aldosterone synthase inhibitor, a phosphodiesterase-5 inhibitor, a vasodilator, a calcium channel blocker, a potassium channel activator, a diuretic, a sympatholitic, a beta-adrenergic blocking drug, an alpha adrenergic blocking drug, a central alpha adrenergic agonist, a peripheral vasodilator, a lipid lowering agent or a metabolic altering agent.