2-benzyl, 3-(pyrimidin-2-yl) substituted pyrazoles useful as sGC stimulators

Inventors

Kim, Charles • Nakai, Takashi • Moore, Joel • Perl, Nicholas Robert • Im, G-yoon Jamie • Barden, Timothy Claude • Iyengar, Rajesh R. • Zimmer, Daniel P. • Fretzen, Angelika • Renhowe, Paul Allan

Assignees

Cyclerion Therapeutics Inc

Abstract

Compound of Table I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.

Core Innovation

The disclosed subject matter includes specific compounds presented as structural depictions and corresponding structure files, including compounds labeled 110–122, 37–62, 70–78, 81–88, 90–96, and 92–117, as well as named compounds such as Compound 4, 6, 17, 18, 29, 39, 74, 98, 99, 109, 110, and 111. The compounds are described as substituted aminopyrimidin-4-ol derivatives, substituted bicyclic heteroaromatic compounds, fluorinated heteroaromatic scaffold analogs, and 2-benzyl, 3-(pyrimidin-2-yl) substituted pyrazole compounds, including pharmaceutically acceptable salts.

The disclosure emphasizes soluble guanylate cyclase (sGC) stimulation, including NO-independent and heme-dependent activation of sGC, leading to increased cyclic GMP (cGMP). The compounds are presented with substituent variations including aryl or heteroaryl (thio) groups, sulfonyl and sulfamoyl motifs, halogens, cyano, carboxamide/acid, amino, O-heterocycle patterns, and fluoro, chloro, methoxy, and trifluoromethyl groups.

The partial content further provides preparation and transformation of intermediates supporting the compound sets, including references to Intermediate 8C, Intermediate-16, Intermediate-0, and Intermediate-25, together with coupling/cyclization routes and general procedures. It also includes examples, characterization data such as 1H NMR, LC-MS, LC/MS/MS, isolated product yields, and pharmaceutical compositions with pharmaceutically acceptable excipients.

Claims Coverage

The independent claims are directed to compounds depicted below or pharmaceutically acceptable salts thereof. Across the provided claim material, the core inventive coverage centers on the depicted compounds and their salts, with dependent claims adding pharmaceutical composition coverage through the inclusion of at least one pharmaceutically acceptable excipient. Two recurring inventive features are present.

Overall, the claim coverage is directed to the depicted compounds and their pharmaceutically acceptable salts, with dependent claims extending to pharmaceutical compositions containing those compounds and pharmaceutically acceptable excipients.

Stated Advantages

Documented Applications