Blaser, Adrian; Palmer, Brian D.; Sutherland, Hamish S.; Kmentova, Iveta; Franzblau, Scott G.; Wan, Baojie; Wang, Yuehong; Ma, Zhenkun; Thompson, Andrew M.; Denny, William A. published the artcile< Structure-Activity Relationships for Amide-, Carbamate-, And Urea-Linked Analogues of the Tuberculosis Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)>, Name: 2-(Trifluoromethoxy)benzoyl chloride, the main research area is structure activity relationship Mycobacterium tuberculosis infection drug imidazooxazine preparation; PA 824 analog preparation SAR tuberculosis infection drug.
Analogs of clin. tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824, I), in which the OCH2 linkage was replaced with amide, carbamate, and urea functionality, were investigated as an alternative approach to address oxidative metabolism, reduce lipophilicity, and improve aqueous solubility Several soluble monoaryl examples displayed moderately improved (∼2- to 4-fold) potencies against replicating Mycobacterium tuberculosis but were generally inferior inhibitors under anaerobic (nonreplicating) conditions. More lipophilic biaryl derivatives mostly displayed similar or reduced potencies to these in contrast to the parent biaryl series. The leading biaryl carbamate demonstrated exceptional metabolic stability and a 5-fold better efficacy than the parent drug in a mouse model of acute M. tuberculosis infection but was poorly soluble Bioisosteric replacement of this biaryl moiety by arylpiperazine resulted in a soluble, orally bioavailable carbamate analog providing identical activity in the acute model, comparable efficacy to OPC-67683 in a chronic infection model, favorable pharmacokinetic profiles across several species, and enhanced safety.
Journal of Medicinal Chemistry published new progress about Homo sapiens. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Name: 2-(Trifluoromethoxy)benzoyl chloride.
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Chlorides – an overview | ScienceDirect Topics