Substituent activity relationship studies on new azolo benzoxazepinyl oxazolidinones

The synthesis of a series of tricyclic oxazolidinones is disclosed. SAR studies on these novel compounds and evaluation of a lead compound are reported. In an effort to discover potent antibacterials based on the entropically favored ‘bioactive conformation’ approach, a series of novel tricyclic mol...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry Vol. 14; no. 23; pp. 8032 - 8042
Main Authors:	Das, Jagattaran, Sitaram Kumar, M., Subrahmanyam, D., Sastry, T.V.R.S., Prasad Narasimhulu, C., Laxman Rao, C.V., Kannan, M., Roshaiah, M., Awasthi, Riti, Patil, Santosh N., Sarnaik, H.M., Rao Mamidi, N.V.S., Selvakumar, N., Iqbal, Javed
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-12-2006 Elsevier Science
Subjects:	Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - pharmacology Antibacterial Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Benzazepines - chemistry Biological and medical sciences Linezolid Medical sciences Molecular Mimicry Oxazolidinones Oxazolidinones - chemical synthesis Oxazolidinones - pharmacology Pharmacology. Drug treatments Pyrroles - chemistry Structure-Activity Relationship Tricyclic Linezolid Antibacterial Tricyclic Oxazolidinones Molecular rigidity Rodentia Oral administration Steric hindrance Tricyclic compound In vitro In vivo Vertebrata Mammalia Structure activity relation Mouse Animal Oxazolidinone derivative Antibacterial agent Pharmacokinetics Chemical synthesis Oxazole derivatives Conformation
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Summary:	The synthesis of a series of tricyclic oxazolidinones is disclosed. SAR studies on these novel compounds and evaluation of a lead compound are reported. In an effort to discover potent antibacterials based on the entropically favored ‘bioactive conformation’ approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C–N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2006.07.040