Journal of Medicinal Chemistry
Article
selectivity of mammalian target of rapamycin (mTOR) inhibitors.
J. Med. Chem. 2009, 52 (24), 7942−7945.
lithium aluminum hydride; DMF, dimethylformamide; m-CPBA,
meta-chloro per benzoic acid; KOH, potassium hydroxide; THF,
tetrahydrofuran; DCM, dichloromethane; NADPH, nicotinamide
adenine dinucleotide phosphate; NMP, N-methyl-2-pyrrolidone;
SSV, standard suspension vehicle; DET, 5% DMSO and
5% EtOH in tetraglycol; PCC, Pyridinium chlorochromate
(11) (a) Bueno-Calderon, J. M.; Fiandor-Roman, J. M.; Puente-
Felipe, M.; Chicharrp-Gonzalo, J.; Kusalakumari Sukamar, S. K.;
Maleki, M., Phosphate ester of a 4-pyridone derivative and its use in
the chemotherapy of parasitic infections. WO2010094738, 26th
August 2010; (b) Chou, L. C.; Chen, C. T.; Lee, J. C.; Way, T. D.;
Huang, C. H.; Huang, S. M.; Teng, C. M.; Yamori, T.; Wu, T. S.; Sun,
C. M.; Chien, D. S.; Qian, K.; Morris-Natschke, S. L.; Lee, K. H.;
Huang, L. J.; Kuo, S. C. Synthesis and preclinical evaluations of 2-(2-
fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phos-
phate (CHM-1-P-Na) as a potent antitumor agent. J. Med. Chem.
2010, 53 (4), 1616−1626.
REFERENCES
■
(1) (a) Snow, R. W.; Trape, J. F.; Marsh, K. The past, present and
future of childhood malaria mortality in Africa. Trends Parasitol. 2001,
17 (12), 593−597. (b) White, N. J. Antimalarial drug resistance.
J. Clin. Invest. 2004, 113 (8), 1084−1092.
(2) Malaria; Fact sheet Number 94; World Health Organization:
Geneva, Switzerland, 2009.
(12) Cundy, K. C.; Annamalai, T.; Bu, L.; De Vera, J.; Estrela, J.; Luo,
W.; Shirsat, P.; Torneros, A.; Yao, F.; Zou, J.; Barrett, R. W.; Gallop,
M. A. XP13512 [( )-1-([(alpha-isobutanoyloxyethoxy)carbonyl]
aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug:
II. Improved oral bioavailability, dose proportionality, and colonic
absorption compared with gabapentin in rats and monkeys.
J. Pharmacol. Exp. Ther. 2004, 311 (1), 324−333.
(3) (a) Burrows, J. N.; Chibale, K.; Wells, T. N. The state of the art
in anti-malarial drug discovery and development. Curr. Top. Med.
Chem. 2011, 11 (10), 1226−1254; (b) A research agenda for malaria
eradication: drugs. PLoS Med. 2011, 8 (1), e1000402.
(4) 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.
Identification, design and biological evaluation of bisaryl quinolones
targeting Plasmodium falciparum Type II NADH:quinone oxidore-
ductase (PfNDH2). J. Med. Chem. 2012, DOI: 10.1021/jm201179h.
(5) (a) Biagini, G. A.; Viriyavejakul, P.; O’Neill P, M.; Bray, P. G.;
Ward, S. A. Functional characterization and target validation of
alternative complex I of Plasmodium falciparum mitochondria.
Antimicrob. Agents Chemother. 2006, 50 (5), 1841−1851. (b) Fisher,
N.; Bray, P. G.; Ward, S. A.; Biagini, G. A. The malaria parasite type II
NADH:quinone oxidoreductase: an alternative enzyme for an
alternative lifestyle. Trends Parasitol. 2007, 23 (7), 305−310.
(6) Fisher, N.; Warman, A. J.; Ward, S. A.; Biagini, G. A. Chapter 17
Type II NADH: quinone oxidoreductases of Plasmodium falciparum
and Mycobacterium tuberculosis kinetic and high-throughput assays.
Methods Enzymol. 2009, 456, 303−320.
(13) Biagini, G. A.; Fisher, N.; Berry, N.; Stocks, P. A.; Meunier, B.;
Williams, D. P.; Bonar-Law, R.; Bray, P. G.; Owen, A.; O’Neill, P. M.;
Ward, S. A. Acridinediones: selective and potent inhibitors of the
malaria parasite mitochondrial bc1 complex. Mol. Pharmacol. 2008,
73 (5), 1347−1355.
(14) Peters, W.; Robinson, B. L. Malaria; Academic Press: San
Diego, 1999.
(15) Trager, W.; Jensen, J. B. Human malaria parasites in continuous
culture. Science 1976, 193 (4254), 673−675.
(16) Smilkstein, M.; Sriwilaijaroen, N.; Kelly, J. X.; Wilairat, P.;
Riscoe, M. Simple and inexpensive fluorescence-based technique for
high-throughput antimalarial drug screening. Antimicrob. Agents
Chemother. 2004, 48 (5), 1803−1806.
(7) (a) Durant, J. L.; Leland, B. A.; Henry, D. R.; Nourse, J. G.
Reoptimization of MDL keys for use in drug discovery. J. Chem. Inf.
Comput. Sci. 2002, 42 (6), 1273−1280. (b) Rogers, D.; Hahn, M.
Extended-connectivity fingerprints. J. Chem. Inf. Model. 2010, 50 (5),
742−754. (c) Willett, P. Similarity-based virtual screening using 2D
fingerprints. Drug Discovery Today 2006, 11 (23−24), 1046−1053.
(d) Geppert, H.; Vogt, M.; Bajorath, J. Current trends in ligand-based
virtual screening: molecular representations, data mining methods,
new application areas, and performance evaluation. J. Chem. Inf. Model.
2010, 50 (2), 205−216. (e) Liu, K.; Feng, J.; Young, S. S. PowerMV: A
software environment for molecular viewing, descriptor generation,
data analysis and hit evaluation. J. Chem. Inf. Model. 2005, 45 (2),
515−522.
(8) (a) Sutherland, H. S.; Blaser, A.; Kmentova, I.; Franzblau, S. G.;
Wan, B.; Wang, Y.; Ma, Z.; Palmer, B. D.; Denny, W. A.; Thompson,
A. M. Synthesis and structure-activity relationships of antitubercular
2-nitroimidazooxazines bearing heterocyclic side chains. J. Med. Chem.
2010, 53 (2), 855−866. (b) Kmentova, I.; Sutherland, H. S.; Palmer,
B. D.; Blaser, A.; Franzblau, S. G.; Wan, B.; Wang, Y.; Ma, Z.; Denny,
W. A.; Thompson, A. M. Synthesis and structure-activity relationships
of aza- and diazabiphenyl analogues of the antitubercular drug (6S)-2-
nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo
[2, 1-b][1,3]oxazine (PA-824). J. Med. Chem. 2010, 53, 855−866.
(9) (a) Luo, F.-T.; Ravi, V. K.; Xue, C. The novel reaction of ketones
with o-oxazoline-substituted anilines. Tetrahedron 2006, 62, 9365−
9372. (b) 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 (9), 2845−2852.
(10) Zask, A.; Kaplan, J.; Verheijen, J. C.; Richard, D. J.; Curran, K.;
Brooijmans, N.; Bennett, E. M.; Toral-Barza, L.; Hollander, I.; Ayral-
Kaloustian, S.; Yu, K. Morpholine derivatives greatly enhance the
1857
dx.doi.org/10.1021/jm201184h | J. Med. Chem. 2012, 55, 1844−1857