Exploration of Alternative Scaffolds for P2Y₁₄ Receptor Antagonists Containing a Biaryl Core.

ABSTRACT: Various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl P2Y₁₄ receptor (P2Y₁₄R) antagonists were synthesized, and affinity was measured in P2Y₁₄R-expressing Chinese hamster ovary cells by flow cytometry. Given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. Rotation of previously identified 1,2,3-triazole attached to the central m-benzoic acid core (25) provided moderate affinity but not indole and benzimidazole substitution of the aryl-triazole. The corresponding P2Y₁₄R region is predicted by homology modeling as a deep, sterically limited hydrophobic pocket, with the outward pointing piperidine moiety b

SUBMITTER: Jung YH 

PROVIDER: S-EPMC8040948 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature