BAY-6096: A Potent, Selective, and Highly Water-Soluble Adrenergic α_2B Antagonist.

ABSTRACT: After acute myocardial infarction, early reperfusion is the most effective strategy for reducing cardiac damage and improving clinical outcome. However, restoring blood flow to the ischemic myocardium can paradoxically induce injury by itself (reperfusion injury), with microvascular dysfunction being one contributing factor. α_2B adrenergic receptors have been hypothesized to be involved in this process. To assess α_2B-related pharmacology, we identified a novel α_2B antagonist by HTS. The HTS hit showed limited α_2A selectivity as well as low solubility and was optimized toward BAY-6096, a potent, selective, and highly water-soluble α_2B antagonist. Key aspects of the optimization were the introduction of a permanently charged pyridinium m

SUBMITTER: Meibom D 

PROVIDER: S-EPMC10108358 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature