title: New gamma-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 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.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, 553-0002, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kokuryo
authors.forename: T
authors.initials: T
authors.lastname: Nakatani
authors.forename: M
authors.initials: M
authors.lastname: Kakinuma
authors.forename: M
authors.initials: M
authors.lastname: Kabaki
authors.forename: K
authors.initials: K
authors.lastname: Kawata
authors.forename: A
authors.initials: A
authors.lastname: Kugimiya
authors.forename: K
authors.initials: K
authors.lastname: Kawada
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Ohtani
mesh_terms: D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D015394:Molecular Structure; D011621:Pteridines / Q000138:chemical synthesis / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D005493:Folic Acid Antagonists; D007166:Immunosuppressive Agents; D008934:Mitogens; C412313:N-(4-(3-(2,4-diamino-7H-pyrrolo(2,3-d)-pyrimidin-5-yl)-1-methylpropyl)benzoyl)-gamma-fluoroglutamic acid; D011621:Pteridines; D011743:Pyrimidines; C036539:fluoresceinated methotrexate; D018698:Glutamic Acid; D008727:Methotrexate