Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Bioorganic & medicinal chemistry, 2013-08, Vol.21 (15), p.4485-4493

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• A series of novel 2-hydroxypyrrolobenzodiazepine-5,11-dione analogues designed through structure based rational hybridization approach were synthesized. Evaluation of all 23 new compounds using ACE inhibition assay, resulted (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 as most potent non-carboxylic acid ACE inhibitor. 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: 0.272μM) 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.