From serendipity to rational antituberculosis drug discovery of mefloquine-isoxazole carboxylic acid esters

Journal of Medicinal Chemistry

Volumn 52, Issue 22, 2009, Pages 6966-6978

  Mao, Jialin ^a,b   Yuan, Hai ^a,c   Wang, Yuehong ^a   Wan, Baojie ^a   Pieroni, Marco ^a   Huang, Qingqing ^a   Van Breemen, Richard B ^a   Kozikowski, Alan P ^a   Franzblau, Scott G ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c PSYCHOGENICS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3,5 ISOXAZOLEDICARBOXYLIC ACID, 3 ETHYL ESTER; 4 (1 ETHYNYLPENTYLOXY) 2,8 BIS(TRIFLUOROMETHYL)QUINOLINE; 4 (1 METHYLPROP 2 YNYLOXY) 2,8 BIS(TRIFLUOROMETHYL)QUINOLINE; 4 (1 PHENYLPROP 2 YNYLOXY) 2,8 BIS(TRIFLUOROMETHYL)QUINOLINE; 4 (1,1 DIMETHYLPROP 2 YNYLOXY) 2,8 BIS(TRIFLUOROMETHYL)QUINOLINE; 4 ETHYNYL 2,8 BIS(TRIFLUOROMETHYL)QUINOLINE; 5 [1 [2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YLOXY] 1 METHYLETHYL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 [1 [2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YLOXY]ETHYL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 [1 [2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YLOXY]PENTYL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 [2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 [2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YLOXYMETHYL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 [[2,8 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YLOXY]PHENYLMETHYL]ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; 5 CHLOROCARBONYL ISOXAZOLE 3 CARBOXYLIC ACID ETHYL ESTER; [[3 (ETHOXYCARBONYL) 5 ISOXAZOLYL]METHYL]TRIPHENYLPHOSPHONIUM BROMIDE; CARBOXYLIC ACID DERIVATIVE; ETHYL 5 [2 (2,6 BIS(TRIFLUOROMETHYL)QUINOLIN 4 YL)VINYL]ISOXAZOLE 3 CARBOXYLATE; ETHYL 5 [2 (4 QUINOLINYL)ETHENYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 [2 (4 QUINOLINYL)ETHENYL] 3 ISOXAZOLECARBOXYLIC ACID; ETHYL 5 [2 (4 QUINOLINYL)ETHYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 [2 (6 QUINOLINYL)ETHENYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 [2 [2,8 BIS(TRIFLUOROMETHYL) 4 QUINOLINYL]ETHENYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 [2 [2,8 BIS(TRIFLUOROMETHYL) 4 QUINOLINYL]ETHYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 [[[2,8 BIS(TRIFLUOROMETHYL) 4 QUINOLINYL]AMINO]CARBONYL] 3 ISOXAZOLECARBOXYLATE; ETHYL 5 BROMOMETHYL 3 ISOXAZOLECARBOXYLATE; ISOXAZOLE DERIVATIVE; MEFLOQUINE; PYRAZINAMIDE; RIFAMPICIN; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL MODIFICATION; CYTOTOXICITY; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTROSPRAY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NEUROTOXICITY; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; SINGLE DRUG DOSE; THIN LAYER CHROMATOGRAPHY; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTITUBERCULAR AGENTS; CERCOPITHECUS AETHIOPS; DRUG DISCOVERY; ESTERS; FEMALE; HUMANS; ISOXAZOLES; MEFLOQUINE; MICE; MICROBIAL SENSITIVITY TESTS; MICROSOMES, LIVER; MYCOBACTERIUM TUBERCULOSIS; VERO CELLS;

EID: 70949108050     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900340a     Document Type: Article

References (11)

1. WHO, WHO Report 2008 Global tuberculosis control - surveillance, planning, financing. 2008.
2. Tripathi, R. P.; Tewari, N.; Dwivedi, N.; Tiwari, V. K. Fighting tuberculosis: an old disease with new challenges. Med. Res. Rev. 2005, 25, 93-131.
3. CDC Trends in Tuberculosis - United States, 2007. Morbidity & Mortality Weekly Report 2008, 57, 281-285.
4. Mao, J.; Wan, B.; Wang, Y.; Franzblau, S. G.; Kozikowski, A. P. HTS, chemical hybridization, and drug design identify a chemically unique antituberculosis agent-coupling serendipity and rational approaches to drug discovery. ChemMedChem 2007, 2, 811-813.
5. Mao, J.; Yuan, H.; Wang, Y.; Wan, B.; Pak, D.; He, R.; Kozikowski, A. P; Franzblau, S. G. Synthesis and Antituberculosis Activity of Novel Mefloquine-Isoxazole Carboxylic Esters as Prodrugs (in preparation).
6. Collins, L.; Franzblau, S. G. Microplate alamar blue assay versus BACTEC460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother. 1997, 41, 1004-1009.
7. Kozikowski, A. P. Methods for the stereoselective cis cyanohydroxylation and carboxyhydroxylation of olefins. J. Org. Chem. 1983, 48, 366-372.
8. Cho, S. H.; Warit, S.; Wan, B.; Hwang, C. H.; Pauli, G. F.; Franzblau, S. G. Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2007, 51 (4), 1380-1385.
9. Zhang, Y.; Permar, S.; Sun, Z. Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide. J. Med. Microbiol. 2002, 51 (1), 42-49.
10. Zhang, Y.; Scorpio, A.; Nikaido, H.; Sun, Z. Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Bacteriol. 1999, 181 (7), 2044-2049. (Pubitemid 29164956)
11. Falzari, K.; Zhu, Z.; Pan, D.; Liu, H.; Hongmanee, P.; Franzblau, S. G. In vitro and in vivo activities of macrolide derivatives against Mycobacteriumtuberculosis. Antimicrob. Agents Chemother. 2005, 49 (4), 1447-1454.