Ullrich, Thomas, Teixeira-Fouchard, Sylvie, Broennimann, Valerie, Stiefl, Nikolaus, Head, Victoria, Kramer, Ina, Guth-Gundel, Sabine, Arista, Luca and Weiler, Sven (2022) Discovery of a novel 2-aminopyrazine-3-carboxamide as a potent and selective inhibitor of Activin Receptor-Like Kinase-2 (ALK2) for the treatment of fibrodysplasia ossificans progressiva. Bioorganic & medicinal chemistry letters. ISSN 1464-3405

Abstract

Inhibition of mutant activin A type-1 receptor ACVR1 (ALK2) signaling by small-molecule drugs is a promising therapeutic approach to treat fibrodysplasia ossificans progressiva (FOP), an ultra-rare disease leading to progressive soft tissue heterotopic ossification with no curative treatment available to date. Here, we describe the synthesis and in vitro characterization of a novel series of 2-aminopyrazine-3-carboxamides that led to the discovery of Compound 23 showing excellent biochemical and cellular potency, selectivity over other BMP and TGFβ signaling receptor kinases, and a favorable in vitro ADME profile.

Item Type:	Article
Date Deposited:	29 Mar 2022 00:45
Last Modified:	29 Mar 2022 00:45
URI:	https://oak.novartis.com/id/eprint/46717