YAKHAK HOEJI (약학회지)
- Volume 40 Issue 3
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- Pages.279-292
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- 1996
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- 0377-9556(pISSN)
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- 2383-9457(eISSN)
Synthesis, Physicochemical Properties and Antitumor Activity of 5-Fluorouracil Prodrugs
5-플로우로우라실 프로드럭의 제조, 물리화학적 성질 및 항암효과
- Jee, Ung-Kil (College of Pharmacy, Chungnam University) ;
- Lee, Gye-Won (College of Pharmacy, Chungnam University)
- Published : 1996.06.01
Abstract
To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU
Keywords
- 5-FU;
- 5-FU prodrugs;
- pKa;
- $LD_{50}$;
- cytotoxicity;
- partition coefficient;
- hydrolysis;
- antitumor activity;
- therapeutic ratio;
- solubility