Orally bioavailable 6-chloro-7-methoxy-4(1 H)-quinolones efficacious against multiple stages of plasmodium

Journal of Medicinal Chemistry

Volumn 57, Issue 21, 2014, Pages 8860-8879

  Cross, R Matthew ^a   Flanigan, David L ^a   Monastyrskyi, Andrii ^a   Lacrue, Alexis N ^b   Sáenz, Fabián E ^b,f   Maignan, Jordany R ^a   Mutka, Tina S ^b   White, Karen L ^c   Shackleford, David M ^c   Bathurst, Ian ^e   Fronczek, Frank R ^d   Wojtas, Lukasz ^a   Guida, Wayne C ^a   Charman, Susan A ^c   Burrows, Jeremy N ^e   Kyle, Dennis E ^b   Manetsch, Roman ^a,g  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

^c MONASH UNIVERSITY   (Australia)

^d LOUISIANA STATE UNIVERSITY   (United States)

^e Medicines for Malaria Venture   (Switzerland)

^f PONTIFICIA UNIVERSIDAD CATÓLICA DEL ECUADOR   (Ecuador)

^g NORTHEASTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (4 TERT BUTYLPHENYL) 6 CHLORO 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 3 (BENZOFURAN 2 YL) 6 CHLORO 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 3 (BENZO[B]THIOPHEN 2 YL) 6 CHLORO 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 3 (BENZO[C][1,2,5]OXADIAZOL 5 YL) 6 CHLORO 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 3 ARYL 6 CHLORO 7 METHOXY 4(1H) QUINOLONE; 4 (6 CHLORO 7 METHOXY 2 METHYL 4 OXO 1,4 DIHYDROQUINOLIN 3YL)BENZALDEHYDE; 6 CHLORO 3 (2 ETHYLPHENYL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (2,3 DIHYDROBENZO[B][1,4]DIOXIN-6 YL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (2,4 DIMETHYLPHENYL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (3,5 DIMETHYLISOXAZOL 4 YL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (4 ISOPROPOXYPHENYL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (4 ISOPROPYLPHENYL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (DIBENZO[B,D]FURAN 4 YL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (FURAN 2 YL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 (FURAN 3 YL) 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 MESITYL 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 3 [6 (DIMETHYLAMINO)PYRIDIN 3 YL] 7 METHOXY 2 METHYLQUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (O TOLYL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (P TOLYL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (PYRIDIN 2 YL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (PYRIDIN 3 YL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (PYRIDIN 4 YL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 (PYRIMIDIN 5 YL)QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 2 METHYL 3 [6 (4 METHYLPIPERAZIN 1 YL)PYRIDIN 3 YL]QUINOLIN 4(1H) ONE; 6 CHLORO 7 METHOXY 3 (4 METHOXYPHENYL) 2 METHYLQUINOLIN 4(1H) ONE; ANTIMALARIAL AGENT; ARTEMISININ; CHLORO 7 METHOXY 4(1H) QUINOLONE DERIVATIVE; QUINOLONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CROSS COUPLING REACTION; DISEASE ELIMINATION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG SCREENING; DRUG SOLUBILITY; EC50; IN VIVO STUDY; MALARIA; MOUSE; NONHUMAN; PARASITEMIA; PHYSICAL CHEMISTRY; PLASMA PROTEIN BINDING; PLASMODIUM; PLASMODIUM BERGHEI; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION; TREATMENT DURATION; TREATMENT RESPONSE; ANIMAL; CHEMISTRY; DRUG EFFECTS; HUMAN; IC50; LIVER MICROSOME; METABOLISM; SYNTHESIS;

ANIMALS; ANTIMALARIALS; HUMANS; INHIBITORY CONCENTRATION 50; MALARIA; MICE; MICROSOMES, LIVER; PARASITEMIA; PLASMODIUM; PLASMODIUM BERGHEI; QUINOLONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84922285353     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500942v     Document Type: Article

References (41)

1. Greenwood, B. M.; Fidock, D. A.; Kyle, D. E.; Kappe, S. H.; Alonso, P. L.; Collins, F. H.; Duffy, P. E. Malaria: progress, perils, and prospects for eradication J. Clin. Invest. 2008, 118, 1266-1276
2. Snow, R. W.; Guerra, C. A.; Noor, A. M.; Myint, H. Y.; Hay, S. I. The global distribution of clinical episodes of Plasmodium falciparum malaria Nature 2005, 434, 214-217
3. World Malaria Report 2012; World Health Organization, (2013.
4. Dondorp, A. M.; Nosten, F.; Yi, P.; Das, D.; Phyo, A. P.; Tarning, J.; Lwin, K. M.; Ariey, F.; Hanpithakpong, W.; Lee, S. J.; Ringwald, P.; Silamut, K.; Imwong, M.; Chotivanich, K.; Lim, P.; Herdman, T.; An, S. S.; Yeung, S.; Singhasivanon, P.; Day, N. P.; Lindegardh, N.; Socheat, D.; White, N. J. Artemisinin resistance in Plasmodium falciparum malaria N. Engl. J. Med. 2009) 361, 455-467
5. White, N. J.; Olliaro, P. Artemisinin and derivatives in the treatment of uncomplicated malaria Med. Trop. (Mars.) 1998, 58, 54-56
6. Noedl, H.; Se, Y.; Schaecher, K.; Smith, B. L.; Socheat, D.; Fukuda, M. M. Artemisinin Resistance in Cambodia 1 Study, C. Evidence of artemisinin-resistant malaria in western Cambodia N. Engl. J. Med. 2008, 359, 2619-2620
7. Plowe, C. V. Malaria: Resistance nailed Nature 2014, 505, 30-31
8. 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.; Menard, 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.; Menard, D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria Nature 2014, 505, 50-55
9. ONeill, P. M.; Ward, S. A.; Berry, N. G.; Jeyadevan, J. P.; Biagini, G. A.; Asadollaly, E.; Park, B. K.; Bray, P. G. A medicinal chemistry perspective on 4-aminoquinoline antimalarial drugs Curr. Top. Med. Chem. 2006, 6, 479-507
10. Stocks, P.; Raynes, K.; Ward, S. Novel Quinoline Antimalarials. In Antimalarial Chemotherapy; Rosenthal, P., Ed.; Humana Press: New Jersey, 2001; pp 235-253.
11. Ray, S.; Madrid, P. B.; Catz, P.; LeValley, S. E.; Furniss, M. J.; Rausch, L. L.; Guy, R. K.; DeRisi, J. L.; Iyer, L. V.; Green, C. E.; Mirsalis, J. C. Development of a new generation of 4-aminoquinoline antimalarial compounds using predictive pharmacokinetic and toxicology models J. Med. Chem. 2010, 53, 3685-3695
12. Vennerstrom, J. L.; Arbe-Barnes, S.; Brun, R.; Charman, S. A.; Chiu, F. C.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo Tomas, J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W. N. Identification of an antimalarial synthetic trioxolane drug development candidate Nature 2004, 430, 900-904
13. Salzer, W.; Timmler, H.; Andersag, H. Über einen neuen, gegen Vogelmalaria wirksamen Verbindungstypus Chem. Ber. 1948, 81, 12-19
14. Casey, A. C. 4(1H)-quinolones. 2. Antimalarial effect of some 2-methyl-3-(1′-alkenyl)-or-3-alkyl-4(1H)-quinolones J. Med. Chem. 1974, 17, 255-256
15. Casey, A. C.; Reynolds, S.; Neubeck, R. Synthesis of Some 2-Methyl-3-(2′-Alkenyl)-4(1h)Quinolones J. Heterocycl. Chem. 1972, 9, 415-418
16. Puri, S. K.; Dutta, G. P. Quinoline esters as potential antimalarial drugs: effect on relapses of Plasmodium cynomolgi infections in monkeys Trans. R. Soc. Trop. Med. Hyg. 1990, 84, 759-760
17. Ryley, J. F.; Peters, W. The antimalarial activity of some quinolone esters Ann. Trop. Med. Parasitol. 1970, 64, 209-222
18. Bueno, J. M.; Manzano, P.; Garcia, M. C.; Chicharro, J.; Puente, M.; Lorenzo, M.; Garcia, A.; Ferrer, S.; Gomez, R. M.; Fraile, M. T.; Lavandera, J. L.; Fiandor, J. M.; Vidal, J.; Herreros, E.; Gargallo-Viola, D. Potent antimalarial 4-pyridones with improved physico-chemical properties Bioorg. Med. Chem. Lett. 2011, 21, 5214-5218
19. Yeates, C. L.; Batchelor, J. F.; Capon, E. C.; Cheesman, N. J.; Fry, M.; Hudson, A. T.; Pudney, M.; Trimming, H.; Woolven, J.; Bueno, J. M.; Chicharro, J.; Fernandez, E.; Fiandor, J. M.; Gargallo-Viola, D.; Gomez de las Heras, F.; Herreros, E.; Leon, M. L. Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials J. Med. Chem. 2008, 51, 2845-2852
20. Cross, R. M.; Monastyrskyi, A.; Mutka, T. S.; Burrows, J. N.; Kyle, D. E.; Manetsch, R. Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity J. Med. Chem. 2010, 53, 7076-7094
21. Winter, R.; Kelly, J. X.; Smilkstein, M. J.; Hinrichs, D.; Koop, D. R.; Riscoe, M. K. Optimization of endochin-like quinolones for antimalarial activity Exp. Parasitol. 2011, 127, 545-551
22. Nilsen, A.; LaCrue, A. N.; White, K. L.; Forquer, I. P.; Cross, R. M.; Marfurt, J.; Mather, M. W.; Delves, M. J.; Shackleford, D. M.; Saenz, F. E.; Morrisey, J. M.; Steuten, J.; Mutka, T.; Li, Y.; Wirjanata, G.; Ryan, E.; Duffy, S.; Kelly, J. X.; Sebayang, B. F.; Zeeman, A. M.; Noviyanti, R.; Sinden, R. E.; Kocken, C. H.; Price, R. N.; Avery, V. M.; Angulo-Barturen, I.; Jimenez-Diaz, M. B.; Ferrer, S.; Herreros, E.; Sanz, L. M.; Gamo, F. J.; Bathurst, I.; Burrows, J. N.; Siegl, P.; Guy, R. K.; Winter, R. W.; Vaidya, A. B.; Charman, S. A.; Kyle, D. E.; Manetsch, R.; Riscoe, M. K. Quinolone-3-diarylethers: a new class of antimalarial drug Sci. Transl. Med. 2013, 5 177ra37
23. Pidathala, C.; Amewu, R.; Pacorel, B.; Nixon, G. L.; Gibbons, P.; Hong, W. D.; Leung, S. C.; Berry, N. G.; Sharma, R.; Stocks, P. A.; Srivastava, A.; Shone, A. E.; Charoensutthivarakul, S.; Taylor, L.; Berger, O.; Mbekeani, A.; Hill, A.; Fisher, N. E.; Warman, A. J.; Biagini, G. A.; Ward, S. A.; ONeill, P. M. Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2) J. Med. Chem. 2012, 55, 1831-1843
24. Biagini, G. A.; Fisher, N.; Shone, A. E.; Mubaraki, M. A.; Srivastava, A.; Hill, A.; Antoine, T.; Warman, A. J.; Davies, J.; Pidathala, C.; Amewu, R. K.; Leung, S. C.; Sharma, R.; Gibbons, P.; Hong, D. W.; Pacorel, B.; Lawrenson, A. S.; Charoensutthivarakul, S.; Taylor, L.; Berger, O.; Mbekeani, A.; Stocks, P. A.; Nixon, G. L.; Chadwick, J.; Hemingway, J.; Delves, M. J.; Sinden, R. E.; Zeeman, A. M.; Kocken, C. H.; Berry, N. G.; ONeill, P. M.; Ward, S. A. Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 8298-8303
25. Cross, R. M.; Namelikonda, N. K.; Mutka, T. S.; Luong, L.; Kyle, D. E.; Manetsch, R. Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones J. Med. Chem. 2011, 54, 8321-8327
26. Cowley, R.; Leung, S.; Fisher, N.; Al-Helal, M.; Berry, N. G.; Lawrenson, A. S.; Sharma, R.; Shone, A. E.; Ward, S. A.; Biagini, G. A.; ONeill, P. M. The development of quinolone esters as novel antimalarial agents targeting the Plasmodium falciparum bc(1) protein complex MedChemComm 2012, 3, 39-44
27. Zhang, Y.; Clark, J. A.; Connelly, M. C.; Zhu, F.; Min, J.; Guiguemde, W. A.; Pradhan, A.; Iyer, L.; Furimsky, A.; Gow, J.; Parman, T.; El Mazouni, F.; Phillips, M. A.; Kyle, D. E.; Mirsalis, J.; Guy, R. K. Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials J. Med. Chem. 2012, 55, 4205-4219
28. Cross, R. M.; Maignan, J. R.; Mutka, T. S.; Luong, L.; Sargent, J.; Kyle, D. E.; Manetsch, R. Optimization of 1,2,3,4-tetrahydroacridin-9(10H)-ones as antimalarials utilizing structure-activity and structure-property relationships J. Med. Chem. 2011, 54, 4399-4426
29. Kelly, J. X.; Smilkstein, M. J.; Brun, R.; Wittlin, S.; Cooper, R. A.; Lane, K. D.; Janowsky, A.; Johnson, R. A.; Dodean, R. A.; Winter, R.; Hinrichs, D. J.; Riscoe, M. K. Discovery of dual function acridones as a new antimalarial chemotype Nature 2009, 459, 270-273
30. Nilsen, A.; Miley, G. P.; Forquer, I. P.; Mather, M. W.; Katneni, K.; Li, Y. X.; Pou, S.; Pershing, A. M.; Stickles, A. M.; Ryan, E.; Kelly, J. X.; Doggett, J. S.; White, K. L.; Hinrichs, D. J.; Winter, R. W.; Charman, S. A.; Zakharov, L. N.; Bathurst, I.; Burrows, J. N.; Vaidya, A. B.; Riscoe, M. K. Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers J. Med. Chem. 2014, 57, 3818-3834
31. Cross, R. M.; Manetsch, R. Divergent route to access structurally diverse 4-quinolones via mono or sequential cross-couplings J. Org. Chem. 2010, 75, 8654-8657
32. Desjardins, R. E.; Canfield, C. J.; Haynes, J. D.; Chulay, J. D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique Antimicrob. Agents Chemother. 1979, 16, 710-718
33. Looareesuwan, S.; Viravan, C.; Webster, H. K.; Kyle, D. E.; Hutchinson, D. B.; Canfield, C. J. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand Am. J. Trop. Med. Hyg. 1996, 54, 62-66
34. Milhous, W. K.; Gerena, L.; Kyle, D. E.; Oduola, A. M. In vitro strategies for circumventing antimalarial drug resistance Prog. Clin. Biol. Res. 1989, 313, 61-72
35. Bueno, J. M.; Herreros, E.; Angulo-Barturen, I.; Ferrer, S.; Fiandor, J. M.; Gamo, F. J.; Gargallo-Viola, D.; Derimanov, G. Exploration of 4(IH)-pyridones as a novel family of potent antimalarial inhibitors of the plasmodial cytochrome bcl Future Med. Chem. 2012, 4, 2311-2323
36. LaPlante, S. R.; Edwards, P. J.; Fader, L. D.; Jakalian, A.; Hucke, O. Revealing atropisomer axial chirality in drug discovery ChemMedChem 2011, 6, 505-513
37. LaPlante, S. R.; L, D. F.; Fandrick, K. R.; Fandrick, D. R.; Hucke, O.; Kemper, R.; Miller, S. P.; Edwards, P. J. Assessing atropisomer axial chirality in drug discovery and development J. Med. Chem. 2011, 54, 7005-7022
38. Ishikawa, M.; Hashimoto, Y. Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry J. Med. Chem. 2011, 54, 1539-1554
39. Lacrue, A. N.; Saenz, F. E.; Cross, R. M.; Udenze, K. O.; Monastyrskyi, A.; Stein, S.; Mutka, T. S.; Manetsch, R.; Kyle, D. E. 4(1H)-Quinolones with liver stage activity against Plasmodium berghei Antimicrob. Agents Chemother. 2013, 57, 417-424
40. Saenz, F. E.; Lacrue, A. N.; Cross, R. M.; Maignan, J. R.; Udenze, K.; Manetsch, R.; Kyle, D. E. 4-(1H)-Quinolones and 1,2,3,4-tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni Antimicrob. Agents Chemother. 2013, 57, 6187-6195
41. Nakai, D.; Kumamoto, K.; Sakikawa, C.; Kosaka, T.; Tokui, T. Evaluation of the protein binding ratio of drugs by a micro-scale ultracentrifugation method J. Pharm. Sci. 2004, 93, 847-854