243641-43-2Relevant academic research and scientific papers
Discovery of an Orally Bioavailable Pan αv Integrin Inhibitor for Idiopathic Pulmonary Fibrosis
Anderson, Niall A.,Campos, Sebastien,Butler, Sharon,Copley, Royston C. B.,Duncan, Ian,Harrison, Stephen,Le, Joelle,Maghames, Rosemary,Pastor-Garcia, Aleix,Pritchard, John M.,Rowedder, James E.,Smith, Claire E.,Thomas, Jack,Vitulli, Giovanni,Macdonald, Simon J. F.
, p. 8796 - 8808 (2019)
The heterodimeric transmembrane αv integrin receptors have recently emerged as potential targets for the treatment of idiopathic pulmonary fibrosis. Herein, we describe how subtle modifications of the central aromatic ring of a series of phenylbutyrate-based antagonists of the vitronectin receptors αvβ3 and αvβ5 significantly change the biological activities against αvβ6 and αvβ8. This resulted in the discovery of a pan αv antagonist (compound 39, 4-40 nM for the integrin receptors named above) possessing excellent oral pharmacokinetic properties in rats (with a clearance of 7.6 mL/(min kg) and a bioavailability of 97%).
Borontribromide-mediated C-C bond formation in cyclic ketones: A transition metal free approach
Ahmad, Imran,Pathak, Vinay,Vasudev, Prema G.,Maurya, Hardesh K.,Gupta, Atul
, p. 24619 - 24634 (2014/07/07)
Borontribromide (BBr3) is a well-known demethylating agent. The current investigation was focused on a new application of borontribromide as a C-C bond forming agent in cyclic ketones. In this study, borontribromide mediated C-C bond formation reactions of tetralones, chromenone, thiochromenone and indanones were explored. A methoxy group containing ketones showed selective C-C bond formation reaction instead of demethylation of the methoxy group. MM2 steric energy calculations for the final products showed that the reaction favored the formation of exo- or endo-cyclic double bond containing products, depending upon their low MM2 steric energy in a specific frame structure, as observed in X-ray crystallography. A comprehensive crystallographic and pi-stacking analysis of product 10a demonstrated the formation of 10a as an enantiomeric mixture, and its centre of inversion was stabilized by a set of three unique pi-pi interactions.
Phenylbutyrates as potent, orally bioavailable vitronectin receptor (integrin αvβ3) antagonists
Miller, William H.,Manley, Peter J.,Cousins, Russell D.,Erhard, Karl F.,Heerding, Dirk A.,Kwon, Chet,Ross, Stephen T.,Samanen, James M.,Takata, Dennis T.,Uzinskas, Irene N.,Yuan, Catherine C. K.,Haltiwanger, R. Curtis,Gress, Catherine J.,Lark, Michael W.,Hwang, Shing-Mei,James, Ian E.,Rieman, David J.,Willette, Robert N.,Yue, Tian-Li,Azzarano, Leonard M.,Salyers, Kevin L.,Smith, Brian R.,Ward, Keith W.,Johanson, Kyung O.,Huffman, William F.
, p. 1483 - 1486 (2007/10/03)
In our continuing efforts to identify small molecule vitronectin receptor antagonists, we have discovered a series of phenylbutyrate derivatives, exemplified by 16, which have good potency and excellent oral bioavailability (approximately 100% in rats). T
