Jung, Sun Hwa Choi, Kihang Pae, Ae Nim Lee, Jae Kyun Choo, Hyunah Keum, Gyochang Cho, Yong Seo Min, Sun-Joon 2024-01-20T08:04:35Z 2024-01-20T08:04:35Z 2021-09-05 2014-12 1477-0520 https://pubs.kist.re.kr/handle/201004/126031 This article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1. The present work clearly demonstrates that a 1,2,3-triazole can be used as a stable oxime surrogate. Furthermore, it suggests that late-stage diversification through coupling reactions of organo-trifluoroborates is suitable for the rapid discovery of biologically active molecules. English ROYAL SOC CHEMISTRY CLICK CHEMISTRY CYCLOADDITION PERSPECTIVES Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate: discovery of potential mPTP blockers Article 10.1039/c4ob01967a 1 ORGANIC & BIOMOLECULAR CHEMISTRY, v.12, no.47, pp.9674 - 9682 ORGANIC & BIOMOLECULAR CHEMISTRY 12 47 9674 9682 scie scopus 000345066100023 2-s2.0-84910011713 Chemistry, Organic Chemistry Article CLICK CHEMISTRY CYCLOADDITION PERSPECTIVES triazoles organotrifluoroborate mPTP blockers