N-aryl-2-aminobenzimidazoles: Novel, efficacious, antimalarial lead compounds

Journal of Medicinal Chemistry

Volumn 57, Issue 15, 2014, Pages 6642-6652

  Ramachandran, Sreekanth ^a   Hameed P , Shahul ^a   Srivastava, Abhishek ^a   Shanbhag, Gajanan ^a   Morayya, Sapna ^a   Rautela, Nikhil ^a   Awasthy, Disha ^a   Kavanagh, Stefan ^a   Bharath, Sowmya ^a   Reddy, Jitendar ^a   Panduga, Vijender ^a   Prabhakar, K R ^a   Saralaya, Ramanatha ^a   Nanduri, Robert ^a   Raichurkar, Anandkumar ^a   Menasinakai, Sreenivasaiah ^a   Achar, Vijayashree ^a   Jiménez Díaz, María Belén ^d   Martínez, María Santos ^d   Angulo Barturen, Iñigo ^d   Ferrer, Santiago ^d   Sanz, Laura María ^d   Gamo, Francisco Javier ^d   Duffy, Sandra ^c   Avery, Vicky M ^c   Waterson, David ^b   Lee, Marcus C S ^e   Coburn Flynn, Olivia ^e   Fidock, David A ^e   Iyer, Pravin S ^a   Narayanan, Shridhar ^a   Hosagrahara, Vinayak ^a   Sambandamurthy, Vasan K ^a   more..

^a ASTRAZENECA   (United Kingdom)

^b International Center Cointrin   (Switzerland)

^c GRIFFITH UNIVERSITY   (Australia)

^d GLAXOSMITHKLINE   (Spain)

^e Department of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 [ 1 METHYLPIPERIDIN 4 YL] N [ 5 (TRIFLUOMETHYL)PYRIDIN 2 YL] 1H BENZO[D]IMIDAZOL 2 AMINE; ANTIMALARIAL AGENT; ARTEMISININ; ATOVAQUONE; BENZIMIDAZOLE DERIVATIVE; CHLOROQUINE; IMIDAZOLE DERIVATIVE; PYRIMETHAMINE; UNCLASSIFIED DRUG; 6-(1-METHYLPIPERIDIN-4-YL)-N-(5-(TRIFLUOROMETHYL)PYRIDIN-2-YL)-1H-BENZO(D)IMIDAZOL-2-AMINE; AMINOPYRIDINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIMALARIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASSAY; BLOOD; CONTROLLED STUDY; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG SCREENING; DRUG SOLUBILITY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; LIVER MICROSOME; MALARIA; MAXIMUM PLASMA CONCENTRATION; MEDICINAL CHEMISTRY; MOUSE; NONHUMAN; PARASITE; PARASITE REDUCTION RATIO ASSAY; PLASMODIUM BERGHEI; PLASMODIUM BERGHEI INFECTION; PLASMODIUM FALCIPARUM; RAT; REDUCTION; SURVIVAL RATE; ANIMAL; CHEMISTRY; DRUG EFFECTS; METABOLISM; MORTALITY; SCID MOUSE; STRUCTURE ACTIVITY RELATION;

AMINOPYRIDINES; ANIMALS; ANTIMALARIALS; BENZIMIDAZOLES; HEPATOCYTES; HUMANS; MALARIA; MICE, SCID; MICROSOMES, LIVER; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84906075395     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500715u     Document Type: Article

References (20)

1. WHO. World MalariaReport (2013. http://www.who.int/malaria/publications/ world-malaria-report-2013/en/.
2. Ariey, F.; Witkowski, B.; Amaratunga, C.; Beghain, J.; Langlois, A. C.; Khim, N.; Kim, S.; Duru, V.; Bouchier, C.; Ma, L.; Lim, P.; Leang, R.; Duong, S.; Sreng, S.; Suon, S.; Chuor, C. M.; Bout, D. M.; Ménard, S.; Rogers, W. O.; Genton, B.; Fandeur, T.; Miotto, O.; Ringwald, P.; Le Bras, J.; Berry, A.; Barale, J. C.; Fairhurst, R. M.; Benoit-Vical, F.; Mercereau-Puijalon, O.; Ménard, D. A molecular marker of artemisinin resistant Plasmodium falciparum malaria Nature 2014) 505, 50-55
3. Burrows, J. N.; Burlot, E.; Campo, B.; Cherbuin, S.; Jeanneret, S.; Leroy, D.; Spangenberg, T.; Waterson, D.; Wells, T. N.; Willis, P. Antimalarial drug discovery-the path towards eradication Parasitology 2014, 141, 128-139
4. Burrows, J. N.; Hooft van Huijsduijnen, R.; Moehrle, J.; Oeuvray, C.; Wells, T. N. Designing the next generation of medicines for malaria control and eradication Malar. J. 2013, 12, 187-206
5. Duffy, S.; Avery, V. M. Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening Am. J. Trop. Med. Hyg. 2012, 86, 84-92
6. Johnson, J. D.; Dennull, R. A.; Gerena, L.; Lopez-Sanchez, M.; Roncal, N. E.; Waters, N. C. Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening Antimicrob. Agents Chemother. 2007, 51, 1926-1933
7. Shirude, P. S.; Shandil, R.; Sadler, C.; Naik, M.; Hosagrahara, V.; Hameed, S.; Shinde, V.; Bathula, C.; Humnabadkar, V.; Naveen Kumar, C. N.; Reddy, J.; Panduga, V.; Sharma, S.; Ambady, A.; Hegde, N.; Whiteaker, J.; McLaughlin, R. E.; Gardner, H.; Madhavapeddi, P.; Ramachandran, V.; Kaur, P.; Narayan, A.; Guptha, S.; Awasthy, D.; Narayan, C.; Mahadevaswamy, J.; Vishwas, K. G.; Ahuja, V.; Srivastava, A.; Prabhakar, K. R.; Bharath, S.; Kale, R.; Ramaiah, M.; Roy Choudhury, N.; Sambandamurthy, V. K.; Solapure, S.; Iyer, P. S.; Narayanan, S.; Chatterji, M. Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo J. Med. Chem. 2013, 56, 9701-9708
8. Dalvie, D.; Smith, E.; Deese, A.; Bowlin, S. In vitro metabolic activation of thiabendazole via 5-hydroxythiabendazole: Identification of a glutathione conjugate of 5-hydroxythiabendazole Drug Metab. Dispos. 2006, 34, 709-717
9. Kwak, Y.; Coppola, G.; Forster, C. J.; Gilmore, T. A.; Gong, Y.; Kanter, A.; Neubert, A.; Stroup, B.; Szklennik, P.; Glowienke, S.; Stadelmann, P.; Bell, L.; Bickford, S.; Gangl, E.; Gunduz, M.; Jain, M.; Zhan, J.; Serrano-Wu, M. H. A new structural alert for benzimidazoles: 2,6-dimethylphenyl substituents increase mutagenic potential and time-dependent CYP3A4 inhibition risk Bioorg. Med. Chem. Lett. 2011, 21, 1422-1424
10. Bolton, J. L.; Trush, M. A.; Penning, T. M.; Dryhurst, G.; Monks, T. J. Role of quinones in toxicology Chem. Res. Toxicol. 2000, 13, 135-160
11. Park, B. K.; Boobis, A.; Clarke, S. Managing the challenge of chemically reactive metabolites in drug development Nat. Rev. Drug Discovery 2011, 10, 292-306
12. Scholz, K.; Dekant, W.; Volkel, W.; Pahler, A. Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer J. Am. Soc. Mass Spectrom. 2005, 16, 1976-1984
13. Stachulski, A. V.; Baillie, T. A.; Park, B. K.; Obach, R. S.; Dalvie, D. K.; Williams, D. P.; Srivastava, A.; Regan, S. L.; Antoine, D. J.; Goldring, C. E.; Chia, A. J.; Kitteringham, N. R.; Randle, L. E.; Callan, H.; Castrejon, J. L.; Farrell, J.; Naisbitt, D. J.; Lennard, M. S. The generation, detection, and effects of reactive drug metabolites Med. Res. Rep. 2013, 33, 985-1080
14. Chawira, A. N.; Warhurst, D. C.; Robinson, B. L.; Peters, W. The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice Trans. R. Soc. Trop. Med. Hyg. 1987, 81, 554-558
15. Angulo-Barturen, I.; Jiménez-Díaz, M. B.; Mulet, T.; Rullas, J.; Herreros, E.; Ferrer, S.; Jiménez, E.; Mendoza, A.; Regadera, J.; Rosenthal, P. J.; Bathurst, I.; Pompliano, D. L.; Gómez de las Heras, F.; Gargallo-Viola, D. A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes PLoS One 2008, 3, e2252
16. Rottmann, M.; McNamara, C.; Yeung, B. K.; Lee, M. C.; Zou, B.; Russell, B.; Seitz, P.; Plouffe, D. M.; Dharia, N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; Gonzalez-Paez, G. E.; Lakshminarayana, S. B.; Goh, A.; Suwanarusk, R.; Jegla, T.; Schmitt, E. K.; Beck, H. P.; Brun, R.; Nosten, F.; Renia, L.; Dartois, V.; Keller, T. H.; Fidock, D. A.; Winzeler, E. A.; Diagana, T. T. Spiroindolones, a potent compound class for the treatment of malaria Science 2010, 329, 1175-1180
17. McNamara, C. W.; Lee, M. C.; Lim, C. S.; Lim, S. H.; Roland, J.; Nagle, A.; Simon, O.; Yeung, B. K.; Chatterjee, A. K.; McCormack, S. L.; Manary, M. J.; Zeeman, A. M.; Dechering, K. J.; Kumar, T. R.; Henrich, P. P.; Gagaring, K.; Ibanez, M.; Kato, N.; Kuhen, K. L.; Fischli, C.; Rottmann, M.; Plouffe, D. M.; Bursulaya, B.; Meister, S.; Rameh, L.; Trappe, J.; Haasen, D.; Timmerman, M.; Sauerwein, R. W.; Suwanarusk, R.; Russell, B.; Renia, L.; Nosten, F.; Tully, D. C.; Kocken, C. H.; Glynne, R. J.; Bodenreider, C.; Fidock, D. A.; Diagana, T. T.; Winzeler, E. A. Nature 2013, 504, 248-253
18. Sanz, L. M.; Crespo, B.; De-Cózar, C.; Ding, X. C.; Llergo, J. L.; Burrows, J. N.; García-Bustos, J. F.; Gamo, F. J. P. falciparum in vitro killing rates allow to discriminate between different antimalarial mode-of-action PLoS One 2012, 7, e30949
19. Le Manach, C.; Scheurer, C.; Sax, S.; Schleiferböck, S.; Cabrera, D. G.; Younis, Y.; Paquet, T.; Street, L.; Smith, P.; Ding, X. C.; Waterson, D.; Witty, M. J.; Leroy, D.; Chibale, K.; Wittlin, S. Fast in vitro methods to determine the speed of action and the stage-specificity of anti-malarials in Plasmodium falciparum Malar. J. 2013, 16, 424-430
20. McMillian, M. K.; Li, L.; Parker, J. B.; Patel, L.; Zhong, Z.; Gunnett, J. W.; Powers, W. J.; Johnson, M. D. An improved resazurin-based cytotoxicity assay for hepatic cells Cell Biol. Toxicol. 2002, 18, 157-173