Structure activity relationships of new inhibitors of mammalian 2, 3-oxidosqualene cyclase designed from isoquinoline derivatives.

J Binet, D Thomas, A Benmbarek, D Fornel…

Index: Binet, Jean; Thomas, Didier; Benmbarek, Abdellah; De Fornel, Daniel; Renaut, Patrice Chemical and Pharmaceutical Bulletin, 2002 , vol. 50, # 3 p. 316 - 329

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Citation Number: 12

Abstract

We have designed more potent inhibitors from the previously reported LF 05-0038, a 6- isoquinolinol based inhibitor of 2, 3-oxidosqualene cyclase (IC 50: 1.1 μM). Replacement of the 3-OH group by various 3-substituted amino groups, and modification of the alkyl chain borne by the endocyclic nitrogen led to inhibitors with IC 50 in the range of 0.15 to 1 μM. In a second step, opening of the bicyclic ring system afforded the corresponding ...