Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 21, Issue 15, Pages 4485-4493Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.05.031
Keywords
ACE Inhibitors; Benzodiazepines; Hypertension; Molecular hybridization; Proline
Funding
- C P C Division, IICT, Hyderabad [NWP 0054, NWP 0055, SMiLE CSC 0111, ORIGIN CSC 0108, MLP 0002]
- Department of Biotechnology (DBT)
- CSIR
Ask authors/readers for more resources
A series of novel 10-substituted 2-hydroxypyrrolobenzodiazepine-5,11-diones designed through structure based rational hybridization approach, synthesized by the cyclodehydration of isotonic anhydride with (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid followed by N-substitution, were evaluated as angiotensin converting enzyme (ACE) inhibitors. Among all the new compounds screened (2R, 11aS)-10-((4-bromothiophen-2-yl)methyl)-2-hydroxy-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11 (10H,11aH)dione, 5v (IC50: 0.272 mu M) emerged as most active non-carboxylic acid ACE inhibitor with minimal toxicity comparable to clinical drugs Lisinopril, Benazepril and Ramipril. Favorable binding characteristics in docking studies also supported the experimental results. (C) 2013 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available