TRIAZOLO-PYRAZINYL DERIVATIVES USEFUL AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS

摘要

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.

主权项

1. A compound having structural Formula I:or a pharmaceutically acceptable salt thereof wherein
C* indicates a potential chiral carbon atom; R1 is
(1) hydrogen(2) (C1-6)alkyl,(3) halo(C1-6)alkyl,(4) (C1-6)alkyl-O—,(5) halo(C1-6)alkyl-O—,(6) (C1-6)alkyl-NH—,(7) halo(C1-6)alkyl-NH—,(8) —(C1-3)alkyl-(C3-7)cycloalkyl,(9) —(C1-3)alkyl-aryl, wherein aryl is unsubstituted or substituted by one, two, or three R7,(10) aryl unsubstituted or substituted by one, two, or three R7,(11) (C3-7)cycloalkyl, or(12) —(C1-3)alkyl-heteroaryl wherein the heteroaryl is a 5- or 6-membered ring containing one, two, or three heteroatoms independently selected from the group consisting of N, O, and S, and wherein heteroaryl is unsubstituted or substituted by one, two, or three R7; R2 is
(1) (C1-3)alkyl, or(2) (C3-7)cycloalkyl; R3 is
(1) aryl unsubstituted or substituted by one, two, or three R6,(2) five- or six-membered heteroaryl containing one, two, or three heteroatoms independently selected from N, O and S, wherein heteroaryl is unsubstituted or substituted by one, two, or three R6,(3) (C1-3)alkyl, or(4) (C3-7)cycloalkyl; R4 is
(1) hydrogen,(2) (C1-3)alkyl,(3) halo(C1-3)alkyl, or(4) (C3-7)cycloalkyl; R5 is
(1) hydrogen,(2) hydroxy,(3) —N(R8a)(R8b),(4) —COOH,(5) —C(O)NH2,(6) (C1-3)alkyl,(7) (C3-7)cycloalkyl, or(8) four- to six-membered monocyclic heterocyclyl containing 1 N heteroatom, wherein the heterocyclyl is unsubstituted or substituted by one to two R9; each R6 is independently
(1) (C1-3)alkyl,(2) halo(C1-3)alkyl,(3) (C1-3)alkoxy,(4) halo(C1-3)alkoxy,(5) (C3-7)cycloalkyl, unsubstituted or substituted by halo,(6) halo,(7) cyano,(8) hydroxy,(9) —NH2,(10) —(C1-3)alkyl—COOH, or(11) —(C1-3)alkyl-COO(C1-4)alkyl; each R7 is independently
(1) (C1-3)alkoxy,(2) halo,(3) hydroxy, or(4) (C1-3)alkyl; R8a and R8b are independently
(1) hydrogen,(2) (C1-3)alkyl, or(3) (C3-7)cycloalkyl; and R9 is
(1) (C1-3)alkyl,(2) halo(C1-3)alkyl, or(3) hydroxy.