title: Synthesis and antitumor activity of pyrrolo[2,3-d]pyrimidine antifolates with a bridge chain containing a nitrogen atom.
abstract: Novel pyrrolo[2,3-d]pyrimidine antifolates (1a, b and 2a, b) with a nitrogen atom in the bridge chain between the 2,4-diaminopyrrolo[2,3-d]pyrimidine and phenylene rings were designed and efficiently synthesized. These compounds exhibited more potent inhibitory activities than methotrexate (MTX) against the proliferation of human epidermoid carcinoma KB cells and human non-small cell lung carcinoma A549 cells despite their modest dihydrofolate reductase (DHFR)-inhibitory potency.
authors.affiliation: Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Aso
authors.forename: T
authors.initials: T
authors.lastname: Hitaka
authors.forename: K
authors.initials: K
authors.lastname: Yukishige
authors.forename: K
authors.initials: K
authors.lastname: Ootsu
authors.forename: H
authors.initials: H
authors.lastname: Akimoto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008727:Methotrexate / Q000031:analogs & derivatives / Q000737:chemistry; D008838:Microcomputers; D009584:Nitrogen; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C078101:TNP 351; D009584:Nitrogen; D008727:Methotrexate