Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors

Dinesh Addla, Anvesh Jallapally, Abhinav Kanwal, Balasubramanian Sridhar, Sanjay K. Banerjee, Srinivas Kantevari

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 μM) 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.

Original languageEnglish
Pages (from-to)4485-4493
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number15
DOIs
Publication statusPublished - 01-08-2013

Fingerprint

Angiotensin-Converting Enzyme Inhibitors
Ramipril
Lisinopril
Anhydrides
Carboxylic Acids
Inhibitory Concentration 50
Toxicity
Substitution reactions
Acids
Pharmaceutical Preparations
benazepril
pyrrolo(1,2-a)(1,4)diazepine
4-hydroxypyrrolidine

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Addla, Dinesh ; Jallapally, Anvesh ; Kanwal, Abhinav ; Sridhar, Balasubramanian ; Banerjee, Sanjay K. ; Kantevari, Srinivas. / Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 15. pp. 4485-4493.
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Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors. / Addla, Dinesh; Jallapally, Anvesh; Kanwal, Abhinav; Sridhar, Balasubramanian; Banerjee, Sanjay K.; Kantevari, Srinivas.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 15, 01.08.2013, p. 4485-4493.

Research output: Contribution to journalArticle

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