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KMID : 0043319970200030259
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Archives of Pharmacal Research
1997 Volume.20 No. 3 p.259 ~ p.263
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Synthesis and Antitumor Evaluation of Acyclic 1-[-(N^I-2-chloroethyl-N^I-nitrosoureido)alkyl]thymidine Nucleoside Analogues
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Kim Jack-C.
Kim Young-Hyun
Park Jin-Il
Kim Seon-Hee
Choi Soon-Kyu
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Abstract
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In the preparation of acyclic thymidine nucleoside analogues, (or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(-cyanoalkyl)thymine (2a-d) and 1,3-bis(-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with center dotgave the corresponding 1-(aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.(-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-(-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry -powder in anhydrous gave two types of regioisomeric nitrosoureas, 1-[5-(--chloroethyl---nitrosoureido)pentylithymine (5d) and 1-[5-(-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.
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KEYWORD
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Acyclic thymidine nucleoside analygues, 1-[4-(-2-chloroethyl--nitrosoureido) butyl]thymine, Regioisomeric nitrosoureas, In vitro cytotoxicity, Human chronic myelogenous leukemia cell, Mouse, lymphoid neoplasma cell, Mouse mammary caruisoma cell, IC
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