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The finding that 6-(methylthio)-9-beta-D-ribofuranosyl-9H-purine (6) was more toxic to the avian coccidium, Eimeria tenella, than to embryonic chick liver host cells in vitro prompted the synthesis and testing of analogues of this compound. It was revealed that the beta-D-ribofuranosyl moiety was an important structural feature and that several types of 2-substituents in the purine ring decreased efficacy, as did 3-deaza and 8-aza ring modifications of 6. In contrast, the pyrazolo[3,4-d]pyrimidine analogue of 6 (24) was an order of magnitude more active. Moreover, this analogue was 24-fold less toxic to the host cells than was 6. A series of 4-(alkylthio)-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidines was prepared from 4-mercapto-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (23) and various alkyl halides. The most effective compound in this series in vivo, 4-(ethylthio)-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (25), cleared chicks of the parasite at 50 ppm in the diet and was much less toxic than was 24.
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
January 2005,
Nucleosides, nucleotides & nucleic acids,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
September 1984,
Journal of medicinal chemistry,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
August 1996,
Die Pharmazie,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
January 1971,
Journal of the Chemical Society. Perkin transactions 1,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
November 1976,
The Journal of organic chemistry,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
January 2003,
Nucleosides, nucleotides & nucleic acids,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
August 1985,
Journal of medicinal chemistry,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
July 2009,
Acta crystallographica. Section E, Structure reports online,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
October 1981,
Journal of medicinal chemistry,
T A Krenitsky, and
J L Rideout, and
G W Koszalka, and
R B Inmon, and
E Y Chao, and
G B Elion, and
V S Latter, and
R B Williams
January 2016,
Nucleosides, nucleotides & nucleic acids,
