5-Substituted Pyrimidine Acyclis Nucleoside Analogues 1-Cyanomethyl- and 1-(4-Cyanobutyl)-5-substituted Uracils as Candidate Antitumor Agents

  • Kim, Jack-C. (Department of Chemistry, College of Natural Science) ;
  • Dong, Eun-Soo (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Park, Jin-Il (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Bae, Sang-Duk (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Kim, Seon-Hee (Department of Biochemistry, College of Medicine, Pusan University)
  • 발행 : 1994.12.01

초록

A number of 5-substituted pyrimidine acyclic nucleosides were synthesized and tested for invitor cytotoxicity against four cell lines (j-82 cell, p-388 cell, FM-3A cell and U-938 cell lines). Synthesis of 1-cyanomethyl-5-substituted pyrimidines (1a-e) and 1-(4-cyanobutyl)-5-substituted pyrimidines (2a-e) was acomplished from the series of alkylation reactions ofl 5-substituted uracils with the corresponding chloacetonitrile and 5-chlorovaleronitile in DMSO under $50^{\circ}C$ temperature. These 5-substituted pyrimidine acylic nucleosides (1a-e and 2a-e) exhibited moderate to significant acitivity aginst four cell lines.

키워드

참고문헌

  1. Canceer Res. v.47 Evaluation of a Tetrazolium-based Semiautomated Colorimetric Assay; Assement of Chemosensitivity Testing Carmichael,J.;DeGraff,W.G.;Gazdar,A.F.;Minna,J.D.;Mitchell,J.B.
  2. J. Heterocycl.Chem. v.23 Chemistry and Antiviral Activities of Acyclonucleosides Chu,C.K.;Cutter,S.J.
  3. Progress in Medicinal Chemistry v.23 De Clercq;E.,Walker,R.T.;Ellis,G.P.(ed.);West,G.B.(ed.)
  4. Proc. Natl. Acad. Sci. U.S.A. v.74 Selectivity of Action of an Antiherpetic Agent, 9-(2-Hydroxyethoxymethyl)Guanine Elion,G.B.;Furman,P.A.;Fyfe,J.A.;DeMiranda,P.;Beauchamp,L.;Schaeffer,H.J.
  5. J. Med. Chem. v.25 Studies on the Synthesis of Chemotherapeutics.12. Synthesis and Antitumor Activity of N-phthalidyl-5-Fluorouracil Dericvatives Kametani,T.;Kigasawa,K.;Hiiragi,M.;Wakisawa,K.;Nakazato,K.;Ichikawa,K.;Fukawa,K.;Irino,O.;Nishimura,N.;Okada,T.
  6. J. Med. Chem. v.24 Pyrimidine Acyclic Nucleosides, 1-[2-(hydroxyethoxy)methy]pyrimidines as Candidate Antivirals Kelly,J.A.;Kelsey,J.E.;Hall,W.R.;Krochmal,M.P.;Schaeffer,H.J.
  7. Korean J. Med. Chem. v.4 Synthesis and In Vitro Cytotoxicity of a Homologues Series of 9-[ω-(N'-Methyl-N'-Nitrosoureido)alkyl]purines Kim,J.C.;Bae,S.S.;Kim,S.H.
  8. Arch. Pharm. Res. v.17 Synthesis and Evaluation of Antitumor Activity of a Homologous Series of 1-(ω-Cyanoalkyl)- and 1,3-Bis(ω-Cyanoalkyl) Uracil Nucleoside Analogouses Kim,J.C.;Dong,E.S.;Kim,S.H.;Kim,S.H.
  9. Korean J. Med. Chem. v.2 Synthesis and Evaluation of Uracil-6-carboxaldehyde Schiff Bases as Potential Antitumor Agents. Kim,J.C.;Lee,Y.H.
  10. Antimicrob. Agents Chemother. v.25 Biological Action of Inosine Analogs in Leishmania and Trypanosoma spp. Marr,I.I.;Berens,R.L.;Cohn,N.K.;Nelson,D.J.;Klein,R.
  11. J. Immunol. Methods v.65 Rapid Colorimetric Assy for Celluar growth and Survival Application to Prodiferation and Cytotoxicity Assay Mosmann,T.
  12. Nature v.272 9-(2-Hydroxyethoxymethyl)guanine Activity Against Viruses of the Herpes Group Schaeffer,H.J.;Beauchamp,L.;Miranda,P.;Elion,G.B.;Bauer,D.J.;Collins,P.
  13. Antimicrob. Agent Chmother v.35 Antiproliferative Effects and Mechanism of Action of ICI 195,739 a novel Bis-triazole Derivative Urbina,J.A.;Lazardi,K.;Aguirre,M.;Piras,M.M;Piras,R.