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
Barrett, Tim N. and Taylor, Jonathan A. and Barker, Daniel and Procopiou, Panayiotis A. and Thompson, James D. F. and Barrett, John and Le, Joelle and Lynn, Sean M. and Pogany, Peter and Pratley, Cassie and Pritchard, John M. and Roper, James A. and Rowedder, James E. and Slack, Robert J. and Vitulli, Giovanni and Macdonald, Simon J. F. and Kerr, William J. (2019) 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. Journal of Medicinal Chemistry, 62 (16). pp. 7543-7556. ISSN 0022-2623 (https://doi.org/10.1021/acs.jmedchem.9b00819)
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Abstract
A quaternary ammonium betaine 7 is described which shows exceptional potency and selectivity (1.4 to >3 logs) for the α vβ 6 integrin receptor over the other α v 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 α vβ 6 are described along with related analogues.
ORCID iDs
Barrett, Tim N., Taylor, Jonathan A. ORCID: https://orcid.org/0000-0003-2305-0708, Barker, Daniel, Procopiou, Panayiotis A., Thompson, James D. F., Barrett, John, Le, Joelle, Lynn, Sean M., Pogany, Peter, Pratley, Cassie, Pritchard, John M., Roper, James A., Rowedder, James E., Slack, Robert J., Vitulli, Giovanni, Macdonald, Simon J. F. and Kerr, William J. ORCID: https://orcid.org/0000-0002-1332-785X;-
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Item type: Article ID code: 69425 Dates: DateEvent22 August 2019Published5 August 2019Published Online20 May 2019AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 20 Aug 2019 11:05 Last modified: 11 Nov 2024 12:24 URI: https://strathprints.strath.ac.uk/id/eprint/69425