Abstract：
: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 N(6)-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 N(6)-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 N(6)-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N(6) and no attachment at N-1, or a combined C-10 at N(6) and a CH2Ph at N-1. Any alkyl chain shorter or longer than C-10 at N(6) with a CH2Ph attached at N-1, would result in decrease of biological activity.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Xie M,Lapidus RG,Sadowska M,Edelman MJ,Hosmane RSdoi
10.1016/j.bmc.2016.03.015subject
Has Abstractpub_date
2016-06-15 00:00:00pages
2595-602issue
12eissn
0968-0896issn
1464-3391pii
S0968-0896(16)30164-Xjournal_volume
24pub_type
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