Discovery of novel isoxazolines as anti-tuberculosis agents

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 23, 2007, Pages 6638-6642

  Tangallapally, Rajendra P ^a   Sun, Dianqing ^a   Rakesh, ^a   Budha, Nageshwar ^a   Lee, Robin E B ^a   Lenaerts, Anne J M ^b   Meibohm, Bernd ^a   Lee, Richard E ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b Department of Ecosystem Science and Sustainability   (United States)

Author keywords

Anti tuberculosis agents; Antimicrobial agent; Isoxazolines; Nitrofurans; Tuberculosis

Indexed keywords

ISOXAZOLINE DERIVATIVE; TUBERCULOSTATIC AGENT;

ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; IN VIVO STUDY; MINIMUM INHIBITORY CONCENTRATION; PROTEIN BINDING;

ANIMALS; ANTITUBERCULAR AGENTS; ISOXAZOLES; MICE; MICROBIAL SENSITIVITY TESTS; MYCOBACTERIUM TUBERCULOSIS; NITROFURANS; RATS;

EID: 35649020732     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.09.048     Document Type: Article

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19. 3N (0.2 equiv, catalytic) were dissolved in DCM, and the solution was cooled to 0 °C. Bleach containing 5% NaOCl by weight (3-6 equiv) was added dropwise to the vigorously stirring solution. The biphasic mixture was allowed to warm to room temperature and stirred for 8 h overnight. An additional volume of water (equal to the volume of bleach) was added and the layers were separated. The aqueous layer was extracted two to three additional times with DCM, and the combined organic layers were dried with sodium sulfate, rota-evaporated, and flash column purified to give the product as an enantiomeric mixture. In case of poor solubility of oxime such as nitrofuranyl oxime, a 1:1 mixture of DCM and THF was used as reaction solvent. In this case, for workup, after the reaction the reaction mixture was concentrated on rota-evaporator and the crude product obtained was subjected to water work up. Caution: Nifuraxime is light sensitive hence proper precautions have to be taken during weighing, transferring, etc.
20. R = 5.23 min.
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24. Pharmacokinetic studies of compound 6a.{A table is presented}
25. R = 5.13 min.