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ID: ALA4373707

Journal: J Med Chem

Title: Profile of a Highly Selective Quaternized Pyrrolidine Betaine αvβ6 Integrin Inhibitor-(3S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((1S and 1R,3R)-1-methyl-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-ium-1-yl)butanoate Synthesized by Stereoselective Methylation.

Authors: Barrett TN, Taylor JA, Barker D, Procopiou PA, Thompson JDF, Barrett J, Le J, Lynn SM, Pogany P, Pratley C, Pritchard JM, Roper JA, Rowedder JE, Slack RJ, Vitulli G, Macdonald SJF, Kerr WJ.

Abstract: A quaternary ammonium betaine 7 is described which shows exceptional potency and selectivity (1.4 to >3 logs) for the αvβ6 integrin receptor over the other αv integrins as determined in cell adhesion assays. 7 is prepared by remarkably stereoselective methylation, the origins of which are discussed. The chemical, biological, physicochemical, and pharmacokinetic properties of 7 and its docking into αvβ6 are described along with related analogues.

CiteXplore: 31381331

DOI: 10.1021/acs.jmedchem.9b00819