Preparation and evaluation of trisubstituted pyrimidines as phosphatidylinositol 3-kinase inhibitors. 3-Hydroxyphenol analogues and bioisosteric replacements

…, A Hayes, F di Stefano, F Urban, SJ Shuttleworth…

Index: Large, Jonathan M.; Torr, Jane E.; Raynaud, Florence I.; Clarke, Paul A.; Hayes, Angela; Stefano, Francesca Di; Urban, Frederique; Shuttleworth, Stephen J.; Saghir, Nahid; Sheldrake, Peter; Workman, Paul; McDonald, Edward Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 2 p. 836 - 851

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Citation Number: 16

Abstract

Two classes of trisubstituted pyrimidines related to PI-103 1 have been prepared and their inhibitory activities against phosphatidylinositol 3-kinase (PI3K) p110α were determined. From those with direct 6-aryl substitution compound 11a was the most potent inhibitor with an IC50 value of 62nM, and showed similar activity against other class 1a PI3K isoforms tested, p110β and p110γ. When a linking chain was introduced, as in the second ...