IMIDAZO-PYRAZINE DERIVATIVES USEFUL AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS

摘要

A compound of Formula II or a pharmaceutically acceptable salt thereof, are capable of 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 II, 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 preparations which comprise compounds of Formula II 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-(C3-7)cycloalkyl,(5) (C1-6)alkyl-aryl, wherein aryl is unsubstituted or substituted by cyano, (C3-6)cycloalkyl, (C1-6)alkoxy, or one to three halo,(6) aryl unsubstituted or substituted by cyano, (C3-6)cycloalkyl, (C1-6)alkoxy, or one to three halo, or(7) (C3-6)cycloalkyl; R2 is
(1) (C1-6)alkyl,(2) (C1-6)alkoxy, or(3) (C3-7)cycloalkyl; R3 is
(1) (C1-6)alkyl,(2) (C3-6)cycloalkyl,(3) CO2(C1-6)alkyl,(4) CONR6aR6b,(5) —N(H)C(O)(C1-6)alkyl,(6) —N(H)(C1-6)alkyl,(7) aryl unsubstituted or substituted by (C1-6)alkyl, halo(C1-3)alkyl, (C1-6)alkoxy, halo(C1-6)alkoxy, (C3-6)cycloalkyl, CO2(C1-6)alkyl, CONR6aR6b, or one to three halo,(8) five- or six-membered heteroaryl containing one to three N, O or S heteroatoms, wherein heteroaryl is unsubstituted or substituted by one to two (C1-6)alkyl, halo(C1-6)alkyl, (C1-6)alkoxy, halo(C1-6)alkoxy, (C3-6)cycloalkyl or halo, or(9) (C2-6)alkynyl, R4 is
(1) hydrogen,(2) (C1-6)alkyl,(3) halo(C1-6)alkyl,(4) halo(C1-6)alkoxy,(5) (C1-6)alkoxy,(6) (C3-7)cycloalkyl, or(7) cyano; R5 is
(1) hydrogen,(2) (C1-6)alkyl,(3) halo(C1-6)alkyl,(4) halo,(5) amino,(6) (C1-3)alkyl-aryl,(7) (C1-3)alkyl-(C3-6)cycloalkyl, or(8) cyano; each R6a and R6b are independently
(1) hydrogen,(2) (C1-3)alkyl, or(3) (C3-6)cycloalkyl; R8a and R8b are independently
(1) hydrogen,(2) (C1-6)alkyl,(3) halo(C1-6)alkyl,(4) (C1-6)alkyl-C(O)—O—(C1-6)alkyl,(5) (C3-6)cycloalkyl, unsubstituted or substituted by halo, or(6) (C1-3)alkyl-(C3-6)cycloalkyl; or R8a and R8b along with the nitrogen atom to which they are attached cyclize to form a 4- to 6-membered heterocyclyl containing one or two heteroatoms independently selected from N, O and S, wherein the heterocyclyl is unsubstituted or substituted by one to three R9; and R9 is
(1) (C1-3)alkyl,(2) halo,(3) halo(C1-3)alkyl,(4) (C3-6)cycloalkyl, or(5) —S(O)2—(C1-3)alkyl.