Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 91-97 |
| Number of pages | 7 |
| Journal | Anticancer Research |
| Volume | 26 |
| Issue number | 1 A |
| Publication status | Published - 2006 Jan |
| Externally published | Yes |
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Keywords
- Antitumor agents
- Antiviral agents
- Pyrimidine derivatives
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Modification of pyrimidine derivatives from antiviral agents to antitumor agents. / Kimura, Hiroyuki; Katoh, Takahiro; Kajimoto, Tetsuya; Node, Manabu; Hisaki, Masakatsu; Sugimoto, Yoshikazu; Majima, Tetsuo; Uehara, Yoshimasa; Yamori, Takao.
In: Anticancer Research, Vol. 26, No. 1 A, 01.2006, p. 91-97.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modification of pyrimidine derivatives from antiviral agents to antitumor agents
AU - Kimura, Hiroyuki
AU - Katoh, Takahiro
AU - Kajimoto, Tetsuya
AU - Node, Manabu
AU - Hisaki, Masakatsu
AU - Sugimoto, Yoshikazu
AU - Majima, Tetsuo
AU - Uehara, Yoshimasa
AU - Yamori, Takao
PY - 2006/1
Y1 - 2006/1
N2 - 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.
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.
KW - Antitumor agents
KW - Antiviral agents
KW - Pyrimidine derivatives
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UR - http://www.scopus.com/inward/citedby.url?scp=32144437830&partnerID=8YFLogxK
M3 - Article
VL - 26
SP - 91
EP - 97
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 1 A
ER -