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 |
| |
| Affiliation: | 1. Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA;2. Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, MI, USA;3. Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI, USA |
| |
| 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 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. |
| |
| Keywords: | Organic synthesis and medicinal chemistry Anti-cancer activity Lung, breast, prostate and ovarian cancers In vitro screening Structure–activity relationship (SAR) studies DDX3 as a potential target |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
