Advancement of imidazo[1,2-a]pyridines with improved pharmacokinetics and nM activity vs. Mycobacterium tuberculosis

ACS Medicinal Chemistry Letters

Volumn 4, Issue 7, 2013, Pages 675-679

  Moraski, Garrett C ^a   Markley, Lowell D ^a   Cramer, Jeffrey ^b   Hipskind, Philip A ^b   Boshoff, Helena ^c   Bailey, Mai A ^d   Alling, Torey ^d   Ollinger, Juliane ^d   Parish, Tanya ^d   Miller, Marvin J ^a  

^a UNIVERSITY OF NOTRE DAME   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^d INFECTIOUS DISEASE RESEARCH INSTITUTE   (United States)

Author keywords

imidazo 1,2 a pyridine 3 carboxamides; MDR TB; Mycobacterium tuberculosis; pharmacokinetics; XDR TB

Indexed keywords

6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; [4 (4 FLUOROPHENOXYL)BENZYL]AMINO; [[3 CHLORO 5 (TRIFLUOROMETHYL)PYRIDIN 2 YL]METHYL]AMINO ACID; AMINOSALICYLIC ACID; ETHAMBUTOL; IMIDAZO[1,2 A ]PYRIDINE; IMIDAZO[1,2 ALPHA]PYRIDINE 3 CARBOXAMIDE; ISONIAZID; KANAMYCIN; PYRAZINAMIDE; RIFABUTIN; RIFAMPICIN; STREPTOMYCIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG RESISTANT TUBERCULOSIS; DRUG SCREENING; EXTENSIVELY DRUG RESISTANT TUBERCULOSIS; IN VIVO STUDY; INFECTION; MALE; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MULTIDRUG RESISTANT TUBERCULOSIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PHARMACOKINETICS; PRIORITY JOURNAL;

EID: 84880165405     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400088y     Document Type: Article

References (12)

1. WHO. Global Tuberculosis Control WHO Report 2011; WHO/HTM/TB/2011.16, 2011.
2. Moraski, G. C.; Markley, L. D.; Hipskind, P. A.; Boshoff, H.; Cho, S.; Franzblau, S. G.; Miller, M. J. Advent of imidazo[1,2-a]pyridine-3-carboxamides with potent multi- and extended drug resistant antituberculosis activity ACS Med. Chem. Lett. 2011, 2, 466-470
3. Moraski, G. C.; Markley, L. D.; Chang, M.; Cho, S.; Franzblau, S. G.; Hwang, C. H.; Boshoff, H.; Miller, M. J. Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2- a ]pyridines and isomeric 5,6-fused scaffolds Bioorg. Med. Chem. 2012, 7, 2214-2220
4. Ollinger, J.; Bailey, M-A; Moraski, G. C.; Casey, A.; Florio, S.; Alling, T.; Miller, M. J.; Parish, T. A dual read-out assay to evaluate the potency of compounds active against Mycobacterium tuberculosis PLoS One 2013, 8, e60531
5. Mak, P. M.; Rao, S. P. S.; Tan, M.-P.; Lin, X.; Chyba, J.; Tay, J.; Ng, S.-H.; Tan, B.-H.; Cherian, J.; Duraiswamy, J.; Bifani, P.; Vim, V.; Lee, B.-H.; Ma, N.-L.; Beer, D.; Thayalan, P.; Kuhen, K.; Chatterjee, A.; Supek, F.; Glynne, R.; Zheng, J.; Boshoff, H. I.; Barr, C. E.; Dick, T.; Pethe, K.; Camacho, L. R. A High-Throughput Screen To Identify Inhibitors of ATP Homeostasis in Non-replicating Mycobacterium tuberculosis ACS Chem. Biol. 2012, 7, 1190-1197
6. Abrahams, K. A.; Cox, J. A. G.; Spivey, V. L.; Loman, N. J.; Patten, M. J.; Constantinidoou, C.; Fernandex, R.; Alemparte, C.; Remuinan, M. J.; Barros, D.; Ballell, L.; Besra, G. S. Identification of Novel Imidazo[1,2- a ]pyridine Inhibitors Targeting M. tuberculosis QcrB PLoS One 2012, 7, e52951
7. Ballell, L.; Bates, R. H.; Young, R. J.; Alvarez-Gomez, D.; Alvarez-Ruiz, E.; Barroso, V.; Blanco, D.; Crespo, B.; Escribano, J.; González, R.; Lozano, S.; Huss, S.; Santos-Villarejo, A.; Martín-Plaza, J. J.; Mendoza, A.; Rebollo-Lopez, M. J.; Remuiñan-Blanco, M.; Lavandera, J. L.; Pérez-Herran, E.; Gamo-Benito, F. J.; García-Bustos, J. F.; Barros, D.; Castro, J. P.; Cammack, N. Fueling Open-Source Drug Discovery: 177 Small-Molecule Leads against Tuberculosis ChemMedChem 2013, 8, 313-321
8. Thomas, V. H.; Bhattachar, S.; Hitchingham, L.; Zocharski, P.; Naath, M.; Surendran, N.; Stoner, C. L.; El-Kattan, A. The road map to oral bioavailability: an industrial perspective Expert Opin. Drug Metab. Toxicol. 2006, 2, 591-608
9. Pethe, K.; Sequeira, P. C.; Agarwalla, S.; Rhee, K.; Kuhen, K.; Phong, W. Y.; Patel, V.; Beer, D.; Walker, J. R.; Duraiswamy, J.; Jiricek, J.; Keller, T. H.; Chatterjee, A.; Tan, M. P.; Ujjini, M.; Roa, S. P. S.; Camacho, L.; Bifani, P.; Mak, P. A.; Ma, I.; Barnes, S. W. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy Nat. Commun. 2010, 57, 1-8
10. Stover, C. K.; Warrener, P.; VanDevanter, D. R.; Sherman, D. R.; Arain, T. M.; Langhorne, M. H.; Anderson, S. W.; Towell, J. A.; Yuan, Y.; McMurray, D. N.; Kreiswirth, B. N.; Barry, C. E.; Baker, W. R. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis Nature 2000, 405, 962-966
11. Manjunatha, U. H.; Boshoff, H.; Dowd, C. S.; Zhang, L.; Albert, T. J.; Norton, J. E.; Daniels, L.; Dick, T.; Pang, S. S.; Barry, C. E. Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 431-6
12. Zamek-Gliszczynski, M. J.; Sprague, K. E.; Espada, A.; Raub, T. J.; Morton, S. M.; Manro, J. R.; Molina-Martin, M. How well do Lipophilicity Parameters, MEEKC Microemulsion Capacity Factor, and Plasma Protein Binding Predict CNS Tissue Binding? J. Pharm. Sci. 2012, 5, 1932-40