A carboxylic acid isostere screen of the DHODH inhibitor Brequinar.
Basic Information
ID: ALA4699538
Journal: Bioorg Med Chem Lett
Title: A carboxylic acid isostere screen of the DHODH inhibitor Brequinar.
Authors: DeRatt LG,Christine Pietsch E,Tanner A,Shaffer P,Jacoby E,Wang W,Kazmi F,Zhang X,Attar RM,Edwards JP,Kuduk SD
Abstract: Dihydroorotate dehydrogenase (DHODH) enzymatic activity impacts many aspects critical to cell proliferation and survival. Recently, DHODH has been identified as a target for acute myeloid differentiation therapy. In preclinical models of AML, the DHODH inhibitor Brequinar (BRQ) demonstrated potent anti-leukemic activity. Herein we describe a carboxylic acid isostere study of Brequinar which revealed a more potent non-carboxylic acid derivative with improved cellular potency and good pharmacokinetic properties.
CiteXplore: 33007394
DOI: 10.1016/j.bmcl.2020.127589
Patent ID: ┄