Synthesis and antitumor properties of N1-(hydroxymethyl phenylmethyl) pyrimidine derivatives and their intermediates

被引：5

作者：

Chen, Liying ^{[1
]}

Kode, Nageswara ^{[1
]}

Murthy, Devangachinta ^{[1
]}

Phadtare, Shashikant ^{[1
]}

机构：

[1] Xavier Univ, Coll Pharm, Div Basic Pharmaceut Sci, New Orleans, LA 70125 USA

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2007年 / 4卷 / 04期

关键词：

arylpyrimidines; N1-[(chloromethylphenyl)methyl]pyrimidines; GI(50); antitumor activity;

D O I：

10.2174/157018007784620022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of ortho- meta- and pora-N1-[(chloromethylphenyl)methyl]pyrimidines and N1[(hydroxymethylphenyl)methyl]pyrimidines 4-27 were prepared by the alkylation of various pyrimidine nucleic acid bases with alpha,alpha'-dichloroxylenes followed by acid catalyzed hydrolysis. Compounds 4-27 were evaluated for the cytotoxic activity against a panel NCI-H460 (lung), MCF7 (breast) and SF-268 (CNS) cancer cell lines. The 'active' compounds which reduced growth of cancer cells to ca. 32% or less have been evaluated in the full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute. Specifically, the ortho-N1-[(chloromethylphenyl)methyl]pyrimidines in this series (5, 6 and 7) have demonstrated growth inhibitory effects (GI(50)) on the leukemia (CCRF-CEM, HL-60, K562, MOLT-4, SR) and other cancer cell lines at 10(-5) to 10(-7) M concentrations.

引用

页码：249 / 256

页数：8

共 19 条

[1] Apoptosis at the interface of immunosuppressive and anticancer activities: The examples of two classes of chemical inducers, oxysterols and alkylating agents
Bischoff, PL
Holl, V
Coelho, D
Dufour, P
Luu, B
Weltin, D
[J]. CURRENT MEDICINAL CHEMISTRY, 2000, 7 (07) : 693 - 713
[2] SOME PRACTICAL CONSIDERATIONS AND APPLICATIONS OF THE NATIONAL-CANCER-INSTITUTE IN-VITRO ANTICANCER DRUG DISCOVERY SCREEN
BOYD, MR
PAULI, KD
[J]. DRUG DEVELOPMENT RESEARCH, 1995, 34 (02) : 91 - 109
[3] BOYD MR, 1989, THORACIC ONCOLOGY, P711
[4] 9-[(hydroxymethyl)phenyl]adenines: New aryladenine substrates of adenosine deaminase
Brakta, M
Murthy, D
Ellis, L
Phadtare, S
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (11) : 1489 - 1492
[5] N9- and N7-(chloromethyl phenymethyl)chloropurine derivatives from α, α′-dichloroxylenes:: Synthesis and anticancer activity
Chen, Liying
Kode, Nageswara
Murthy, Devangachinta
Phadtare, Shashikant
[J]. MEDICINAL CHEMISTRY RESEARCH, 2005, 14 (8-9) : 445 - 474
[6] De Clercq E, 2000, REV MED VIROL, V10, P255, DOI 10.1002/1099-1654(200007/08)10:4&lt
[7] 255::AID-RMV282&gt
[8] 3.0.CO
[9] 2-6
[10] Gray GD, 1996, BIOTECHNIQUES, V21, P780

← 1 2 →