New gamma-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immunosuppressive activity.

Y Kokuryo, T Nakatani, M Kakinuma, M Kabaki, K Kawata, A Kugimiya, K Kawada, M Matsumoto, R Suzuki, M Ohtani

Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, 553-0002, Osaka, Japan.

European journal of medicinal chemistry 2000 May

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Our continuing program to develop new antifolate drugs useful against rheumatoid arthritis led us to modify the pteridine ring of gamma-fluoromethotrexate. Pyrrolopyrimidine derivatives 1e and 1t were found to exhibit potent suppressive effects on the responses of both T and B cells to mitogens, although tetrahydropyridopyrimidine derivatives 2e and 2t and quinazoline derivatives 3e, 3t and 4e showed very weak suppressive activities. Thus, conversion of the pteridine ring of gamma-fluoromethotrexate to a pyrrolopyrimidine ring led to a new potential antirheumatic compound.

Citation

Y Kokuryo, T Nakatani, M Kakinuma, M Kabaki, K Kawata, A Kugimiya, K Kawada, M Matsumoto, R Suzuki, M Ohtani. New gamma-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immunosuppressive activity. European journal of medicinal chemistry. 2000 May;35(5):529-34