Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 1. Conversion of 5-Substituent on Oxazolidinone.
- 1 January 2001
- journal article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 49 (4), 347-352
- https://doi.org/10.1248/cpb.49.347
Abstract
A structure-activity relationship (SAR) study on 5-substituted oxazolidinones as an antibacterial agent is described. The oxazolidinones, of which 5-acetylaminomethyl moiety was converted into other functions, were prepared and evaluated for antibacterial activity. Elongation of the methylene chain (8) and conversion of the acetamido moiety into guanidino moiety (12) decreased the antibacterial activity. The replacement of carbonyl oxygen (=O) by thiocarbonyl sulfur (=S) enhanced in vitro antibacterial activity. Especially, compound 16, which had the 5-thiourea group, showed 4-8 stronger in vitro activity than linezolid. Our SAR study revealed that the antibacterial activity was greatly affected by the conversion of 5-substituent.Keywords
This publication has 13 references indexed in Scilit:
- Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial ActivityJournal of Medicinal Chemistry, 1996
- Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial InfectionsJournal of Medicinal Chemistry, 1996
- Phenethylthiazolethiourea (PETT) Compounds, a New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT AnalogsJournal of Medicinal Chemistry, 1995
- 5-Aryl-β,γ butenolide, a new class of antibacterial derived from the N-aryl oxazolidinone DUP 721Bioorganic & Medicinal Chemistry Letters, 1994
- Novel [2-(4-Piperidinyl)ethyl](thio)ureas: synthesis and antiacetylcholinesterase activityJournal of Medicinal Chemistry, 1994
- Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 1. The B groupJournal of Medicinal Chemistry, 1989
- Mechanism of action of DuP 721: inhibition of an early event during initiation of protein synthesisAntimicrobial Agents and Chemotherapy, 1988
- In vitro evaluation of DuP 105 and DuP 721, two new oxazolidinone antimicrobial agentsAntimicrobial Agents and Chemotherapy, 1988
- Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721Antimicrobial Agents and Chemotherapy, 1987
- Preparation of (R)-(+)- and (S)-(-)-4-iodo-1,2-epoxybutane [(R)- and (S)-(2-iodoethyl)oxirane], useful chiral synthonsThe Journal of Organic Chemistry, 1981