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

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