RT Journal Article
SR Electronic
T1 Modification of Pyrimidine Derivatives from Antiviral Agents to Antitumor Agents
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 91
OP 97
VO 26
IS 1A
A1 HIROYUKI KIMURA
A1 TAKAHIRO KATOH
A1 TETSUYA KAJIMOTO
A1 MANABU NODE
A1 MASAKATSU HISAKI
A1 YOSHIKAZU SUGIMOTO
A1 TETSUO MAJIMA
A1 YOSHIMASA UEHARA
A1 TAKAO YAMORI
YR 2006
UL http://ar.iiarjournals.org/content/26/1A/91.abstract
AB 2,4-Diaminopyrimidine derivatives, that were originally developed as antiviral agents, were modified to antitumor agents by: i) introducing an amino group at C-5 on the pyrimidine ring, ii) changing the alkyl group and the ring size of the cycloalkyl group on the β-position of the ω-hydroxyalkylamino group, iii) replacing the phenylalkyl group on the cycloalkyl group with the 3,4,5-trimethoxyphenylalkyl group, iv) the esterification of the primary alcohol with diethyl phosphate and v) introducing the thiomethyl group at C-2 on the pyrimidine ring. Among the 21 compounds prepared, 6, which has cyclobutyl at the β-position, exhibited potent activity towards P-388 leukemia. In addition, 14, with methoxyl groups on the phenyl ring and 17, with the thiomethyl group on the pyrimidine ring, showed specific inhibition for the EGFR protein kinase. Moreover, 15 and 16, which carry the diethyl phosphoryl group on the primary alcohol, exhibited inhibitory activity towards P-glycoprotein. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved