title: Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives.
abstract: Novel pyrimidinyl pyrazole derivatives were synthesized and examined for cytotoxic and antitumor activity. Mannich reaction was employed to construct this scaffold. Among the compounds synthesized, a series of propene derivatives exhibited a potent cytotoxic activity against some tumor cell lines including multidrug resistant cell lines due to the overexpression of P-glycoprotein. The vinyl bond moiety in the scaffold was believed to be required for the cytotoxic activity. Among them, compound 14 g, when administered intraperitoneally, showed potent antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice. This compound also showed high activity against a solid tumor Meth A mouse fibrosarcoma when administered both intraperitoneally and orally.
authors.affiliation: New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Naito
authors.forename: M
authors.initials: M
authors.lastname: Sugimori
authors.forename: I
authors.initials: I
authors.lastname: Mitsui
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Iwahana
authors.forename: M
authors.initials: M
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Hirotani
authors.forename: E
authors.initials: E
authors.lastname: Kumazawa
authors.forename: A
authors.initials: A
authors.lastname: Ejima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines