Structure−Activity Relationships of Antitubercular Nitroimidazoles. 2. Determinants of Aerobic Activity and Quantitative Structure−Activity Relationships

Citations Over TimeTop 10% of 2009 papers

Abstract

The (S)-2-nitro-6-substituted 6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazines have been extensively explored for their potential use as new antituberculars based on their excellent bactericidal properties on aerobic whole cells of Mycobacterium tuberculosis. An oxygen atom at the 2-position of the imidazole ring is required for aerobic activity. Here, we show that substitution of this oxygen by either nitrogen or sulfur yielded equipotent analogues. Acylating the amino series, oxidizing the thioether, or replacing the ether oxygen with carbon significantly reduced the potency of the compounds. Replacement of the benzylic oxygen at the 6-position by nitrogen slightly improved potency and facilitated exploration of the SAR in the more soluble 6-amino series. Significant improvements in potency were realized by extending the linker region between the 6-(S) position and the terminal hydrophobic aromatic substituent. A simple four-feature QSAR model was derived to rationalize MIC results in this series of bicyclic nitroimidazoles.

Related Papers

• → Receptor-Guided Alignment-Based Comparative 3D-QSAR Studies of Benzylidene Malonitrile Tyrphostins as EGFR and HER-2 Kinase Inhibitors(2003)54 cited
• → Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes(2020)8 cited
• → Structural requirements for the binding of colchicine analogs to tubulin: the role of the C-10 substituent(1991)5 cited
• → Theoretical studies on pyrimidine substituent derivatives as dual inhibitors of AP-1 and NF-κB(2009)1 cited
• QSAR STUDY OF 4-BENZYLIDENEAMINO-BENZENESULFONAMIDES AS SELECTIVE COX-2 INHIBITORS(2005)