title: Synthesis and biological activities of novel 5-(2-acylethynyl)uracils.
abstract: 5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase.
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta.
authors.forename: N G
authors.initials: NG
authors.lastname: Kundu
authors.forename: B
authors.initials: B
authors.lastname: Das
authors.forename: C P
authors.initials: CP
authors.lastname: Spears
authors.forename: A
authors.initials: A
authors.lastname: Majumdar
authors.forename: S I
authors.initials: SI
authors.lastname: Kang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: D000964:Antimetabolites, Antineoplastic; D007202:Indicators and Reagents; D011743:Pyrimidines; D014498:Uracil; D013940:Thymidylate Synthase