Design of quinolinedione-based geldanamycin analogues

R Hargreaves, CL David, L Whitesell…

Index: Hargreaves, Robert; David, Cynthia L.; Whitesell, Luke; Skibo, Edward B. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 18 p. 3075 - 3078

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Citation Number: 25

Abstract

Quinoline-5, 8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, and amino substituents should be present at the 6-or 7-position. COMPARE analysis revealed that the LC50 profile of 2-phenyl-6-(2-chloroethylamino) quinoline-5, 8-dione ...