Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and antitumor evaluation of $\alphamethylene-\gamma-butyrolactone-linked$ to 5-substituted uracil nucleic acid bases

  • Kim, Jack-C. (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Kim, Ji-A (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Kim, Si-Hwan (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Park, Jin-Il (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Kim, Seon-Hee (Department of Biochemisty, Collegef of Medicine, Pusan National University) ;
  • Park, Soon-Kyu (Department of Chemistry, Dong-A University) ;
  • Park, Won-Woo (Pusan Junior College Pusan)
  • Published : 1996.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Six, heretofore undescribed, $5^I-Methyl-5^I-(5-Substituted uracil-1-ylmethyl)-2^I-oxo-3^I-methylenetetrahydrofurans(F, Cl, Br, l, CH_3, H)(6a-f)$were synthesized and evaluated against three cell lines (FM-3A, P-388 and U-937). For the preparation of .alpha.-methylene-.gamma.-butyrolactone bearing 5-substituted uracils (6a-f), the effcient Reformatsky type reaction was employed which involves the treatment of ethyl .alpha.(bromomethyl) acrylate and zinc with the respective 5-substituted uracil-1-ylacetones (5a-f). The acetone derivatives (5a-f) were directly obtained by the respective alkylation reaction of 5-substituted uracils with chloroacetone in the presence of $K_{2}$$CO_{3}$(or NaH). These lactone compounds 6a-f exhibited moderate to significant activity in all of the three cell lines, and 6b, 6c and 6e showed significant antitumor activities (inhibitory concentrations ($IC_{50}$) ranged from 1.3-3.8 .mu.g/ml.

Keywords