Antimalarial pyrimidine derivatives and methods of making...

Details Antimalarial pyrimidine derivatives and methods of making... Antimalarial pyrimidine derivatives and methods of making...

2008-05-13

2008-05-13

Berch, Mark (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C544S325000, C514S272000

Reexamination Certificate

active

10386613

ABSTRACT:
Compounds of the formula (I) wherein R1represents a hydrogen atom or a 3-halogen atom, and R2represents a straight-chain alkyl group containing up to 6 carbon atoms, a straight-chain alkyl group containing up to 3 carbon atoms with unsubstituted or substituted aromatic ring, or alkoxycarbonyl substituent at the end position, or aryloxyalkoxyalkyl group have been found to possess antimalarial activity againstPlasmodium falciparumlines, including those resistant against pyrimethamine and other antifolates. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed.

REFERENCES:
patent: 2576939 (1951-12-01), Hitchings et al.
patent: 2594309 (1952-04-01), Hitchings et al.
patent: 2602794 (1952-07-01), Hitchings et al.
patent: 2624731 (1953-01-01), Hitchings et al.
patent: 2680740 (1954-06-01), Jacob
patent: 2688019 (1954-08-01), Hitchings et al.
patent: 3849416 (1974-11-01), Mentha et al.
patent: 3939181 (1976-02-01), Mentha et al.
patent: 3940393 (1976-02-01), Greenspan et al.
patent: 4992444 (1991-02-01), Stevens et al.
patent: 2158068 (1985-11-01), None
Oppenlander et al., “Photooxygenation of 5-Aryl-2,4-diaminopyrimidines leading to 4-Amnio-1,3,5-triazin-2-yl Ketones and, in the Presence of Sodium Borohydride, to 5,6,-dihydro-4(3H)-pyrimidinones”, Helvetica Chimica Acta, vol. 71 1998), pp. 712-717.
Tarnchompoo et al., “Development of 2,4-diaminopyrimidines as antimalarials . . . ”, J. Med. Chem., 2002, 45, 1244-1252.
Baker et al., “Irreversible Enzyme Inhibitors . . . ” J. Med. Chem., 1970, 13 (6), 1143-1148.
Tarnchompoo et al., “Development of 2,5-Diaminopyrimidines . . . ” J.Med.Chem. 2002, 45, 1244-1252.
Nicholas J. White, “Antimalarial Drug Resistance”,The Journal of Clinical Investigation(Apr. 2004), pp. 1084-1092, vol. 113, No. 8, Review Series; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.
Alsia P. Alker et al., “Mutations Associated with Sulfadoxine-Pyrimethamine and Chlorproguanil Resistance inPlasmodium falciparumIsolates from Blantyre, Malawi”,Antimicrobial Agents and Chemotherapy(Sep. 2005), pp. 3919-3921, vol. 49, No. 9; American Society for Microbiology.
Alexis Nzila et al., “Why has the dihydrofolate reductase 164 mutation not consistently been found in Africa yet?”,Transactions of the Royal Society of Tropical Medicine and Hygiene(2005), pp. 341-346, vol. 99; Elsevier.
Russell, P.B. et al. (1951). “2,4-Diaminopyrimidines as Antimalarials. III. 5-Aryl Derivatives,” J. Am. Chem. Soc. 73:3763-3770.
Trager, W. et al., (1976). “Human Malaria Parasites in Continous Culture,” Science, 193:673-675.
Desjardins, R.E. et al. (1979). “Quantitative Assessment of Antimalarial Activity in Vitro by a Semiautomated Microdilution Technique,” Antimicrob. Agents Chemother. 16(6):710-718.
Blaney, J.M. et al. (1984). “Structure-Activity Relationships of Dihydrofolate Reductase Inhibitors,” Chem. Rev. 84:333-407.
Cowman, A.F et al. (Dec. 1988). “Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum,” Proc. Natl. Acad. Sci. USA, 85: 9109-9113.
Peterson, D.S. et al. (Dec. 1988). “Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria,” Proc. Natl. Acad. Sci. USA, 85: 9114-9118.
Peterson, D.S. et al. (Apr. 1990). “Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria,” Proc. Natl. Acad. Sci. USA, 87:3018-3022.
Skehan, P. et al. (1990). “New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening,” J. Natl. Cancer Inst. 82(13):1107-1112.
Barlin, G.B. et al. (1996). “Potential Antimalarials. XXII. Some 2,4-Biamino-5-(3-and 4-trifluoromethylphenyl and 3,4-methylenedioxyphenyl) pyrimidines,” Aust. J. Chem. 49: 647-650.
McKie, J. H. et al. (1998). “Rational Drug Design Approach for Overcoming Drug Resistance: Application to Pyrimethamine Resistance in Malaria,” J. Med. Chem. 41:1367-1370.
Ahmed, A. et al. (2004). “Plasmodium falciparum Isolates in India Exhibit a Progressive Increase in Mutations Associated with Sulfadoxine-Pyrimethamine Resistance,” Antimicrobial Agents and Chemotherapy, 48(3):879-889.
Gregson et al. (2005). “Mechanisms of Resistance of Malaria Parasites to Antifolates,” Pharmacological Reviews, 57(1):117-145.

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