162009-79-2Relevant articles and documents
Synthesis, anticancer activity, and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system This paper is dedicated to Dr. Stewart W. Schneller, Professor of Chemistry, Auburn University, Alabama, on the occasion of his 75th birthday in early 2017
Xie, Min,Lapidus, Rena G.,Sadowska, Mariola,Edelman, Martin J.,Hosmane, Ramachandra S.
, p. 2595 - 2602 (2016/06/08)
Described herein are our limited structure-activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N6-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N6-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N6-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N6 and no attachment at N-1, or a combined C-10 at N6 and a CH2Ph at N-1. Any alkyl chain shorter or longer than C-10 at N6 with a CH2Ph attached at N-1, would result in decrease of biological activity.
