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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.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

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

doi

10.1021/jm801558d

subject

Has Abstract

pub_date

2009-02-26 00:00:00

pages

908-11

issue

4

eissn

0022-2623

issn

1520-4804

pii

10.1021/jm801558d

journal_volume

52

pub_type

杂志文章

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