162009-79-2Relevant academic research and scientific papers
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.
A short synthesis of a novel ring-expanded purine and its nucleoside analogue containing the imidazo[4,5-e][1,3]diazepine ring skeleton with multiple amino substituents attached to the 7-membered ring
Wang,Bhan,Hosmane
, p. 2307 - 2320 (2007/10/02)
The synthesis of 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine (1) and its nucleoside analogue (6) are reported. The heterocycle was prepared in a single step by condensation of 4,5-dicyanoimidazole with guanidine. The 5,7- fused ring structure of 1 was distinguished from the other possible 5:5- fused isomer 2 by preparing the 15N-labeled heterocycle (1*) and exploring its 15N-1H coupling patterns in both 1H and 15N NMR spectra. These spectral patterns also enabled establishment of the triamino tautomeric form of 1 as assigned. Compound 1, a novel ring-expanded ('fat') analogue of purine, is anticipated to be planar and aromatic as predicted by molecular modeling. The 1-benzyl analogue (4), a protocol for the ribosyl analogue 6, was similarly prepared from 1-benzyl-4,5-dicyanoimidazole. The nucleoside 6 was prepared by the modified Vorbruggen ribosylation of 1. The position of ribosylation was unequivocally established by an unambiguous synthesis of 6 from condensation of 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4,5- dicyanoimidazole (7) with guanidine in a solution of sodium methoxide in methanol. The nucleoside 7 was prepared by the Vorbruggen ribosylation of 4,5-dicyanoimidazole.
