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

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.