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 preparations 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:or a pharmaceutically acceptable salt thereof wherein:
X1 and X2 are each independently CR or N; R is —H, halo or cyclopropyl; R1 is —H or —C1-6alkyl unsubstituted or substituted with one to three of —F; R2 is (a) —C1-6alkyl unsubstituted or substituted with:
(i) one to six of —F,(ii) —C3-6cycloalkyl unsubstituted or substituted with one to three of —F, or(iii) phenyl unsubstituted or independently substituted at each occurrence with one to three of halo, —CN, —CH3 or —OCH3; (b) —C3-6cycloalkyl unsubstituted or substituted with one to three of —F, or (c) phenyl unsubstituted or independently substituted at each occurrence with one to three of halo, —CN, —CH3 or —OCH3; R2a is —H or —C1-3alkyl unsubstituted or substituted with one to three of —F; R2b is —H or —C1-3alkyl unsubstituted or substituted with one to three of —F; or R2b is —H and R2 and R2a are joined together with the carbon to which they are both attached to represent
(a) —C3-6cycloalkyl unsubstituted or substituted with one to three of —F, or(b) a 4 to 6 membered heterocycle comprised of carbons and one or two heteroatoms independently selected from N, O or S, wherein the heterocycle is unsubstituted or independently substituted at each occurrence with one to three of halo, —CN, —CH3 or —OCH3; R3 is —C1-6alkyl or —C3-6cycloalkyl; R4 is
(a) a 5-membered heteroaryl ring comprised of at least one and up to three carbon atoms, at least one and up to four N atoms, and optionally one O atom or one S atom;(b) a 6-membered heteroaryl ring comprised of carbon atoms and one or two N atoms; or(c) an 8 to 10 membered bicyclic heteroaryl ring system comprised of carbon atoms and one to two heteroatoms independently selected from N, O or S; wherein R4 is unsubstituted or substituted on an available carbon or nitrogen in the ring or ring system with R6; R6 is selected from:
(a) halo,(b) —C1-6alkyl unsubstituted or substituted with one to three of —F, or —C3-6 cycloalkyl for example but not limited to: (c) —C1-6alkyl substituted with —C3-6 cycloalkyl, such that the cycloalkyl and the alkyl share a common carbon at the point of attachment to each other, wherein said attachment can be with any non-terminal carbon in the alkyl group, for example but not limited to: (d) —C3-6 cycloalkyl, (e) —OC1-6alkyl, (f) —C2-6alkenyl, (g) —C(O)OC1-4alkyl, (h) —C1-6alkyl-C(O)OH, (i) —C1-6alkyl-C(O)OC1-3alkyl, or (j) —CD3; R5 is —H, —OR7 or —NHR7; and R7 is —H, —C1-6alkyl or —C3-6 cycloalkyl.