Document Report Card

ID: ALA1140950

Journal: J Med Chem

Title: Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation.

Authors: Butera JA, Larsen BD, Hennan JK, Kerns E, Di L, Alimardanov A, Swillo RE, Morgan GA, Liu K, Wang Q, Rossman EI, Unwalla R, McDonald L, Huselton C, Petersen JS.

Abstract: Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. Small molecule gap-junction modifiers with improved physical properties were identified from a Zealand Pharma peptide library using pharmaceutical profiling, established SAR around 3, and a putative pharmacophore model for rotigaptide. Activity of the compounds was confirmed in a mouse cardiac conduction block model of arrhythmia. Dipeptide 9f (GAP-134) was identified as a potent, orally active gap-junction modifier for clinical development.

CiteXplore: 19175320

DOI: 10.1021/jm801558d