Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential anti-cancer agents

被引：16

作者：

Devegowda, Vani N. ^{[1
,2
]}

Kim, Jung Hyun ^{[1
]}

Han, Ki-Cheol ^{[1
]}

Yang, Eun Gyeong ^{[1
,2
]}

Choo, Hyunah ^{[1
]}

Pae, Ae Nim ^{[1
,2
]}

Nam, Ghilsoo ^{[1
]}

Choi, Kyung Il ^{[1
,2
]}

机构：

[1] Korea Inst Sci & Technol, Life Sci Res Div, Seoul 136791, South Korea

[2] Univ Sci & Technol, Taejon 305333, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期

关键词：

6-N-Arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one; Anticancer activity; Structure-activity relationship; CANCER-RESEARCH; INHIBITORS; PHOSPHODIESTERASE-5;

D O I：

10.1016/j.bmcl.2010.01.029

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d] pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been tested. The prepared compounds library exhibited significant anticancer activity towards HT-29 colon and DU-145 prostate cancer cell lines. The structure-activity relationships of the 6-N-arylcarboxamidopyrazolo[4,3-d] pyrimidin-7-one scaffold at R-1, R-2 and R-3 have been elucidated. Among the synthesized compounds, 12b was the most active compound with GI(50) value of 0.44 mu M and 1.07 mu M against HT-29 and DU-145 cell lines, respectively, and 13a was the most selective compound towards colon cancer cell line. (C) 2010 Published by Elsevier Ltd.

引用

页码：1630 / 1633

页数：4

共 26 条

[1]

A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability [J].

Allerton, Charlotte M. N. ;

Barber, Christopher G. ;

Beaumont, Kevin C. ;

Brown, David G. ;

Cole, Susan M. ;

Ellis, David ;

Lane, Charlotte A. L. ;

Maw, Graham N. ;

Mount, Natalie M. ;

Rawson, David J. ;

Robinson, Colin M. ;

Street, Stephen D. A. ;

Summerhill, Nicholas W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (12) :3581-3594

[2]

[Anonymous], [No title captured]

[3]

[Anonymous], [No title captured]

[4]

Bartulewicz Danuta, 2004, Farmaco (Lausanne), V59, P211, DOI 10.1016/j.farmac.2003.11.005

[5]

Bell A. S., 1991, [No title captured], Patent No. [EP0463756 A1, 0463756]

[6]

Improving memory: A role for phosphodiesterases [J].

Blokland, A. ;

Schreiber, R. ;

Prickaerts, J. .

CURRENT PHARMACEUTICAL DESIGN, 2006, 12 (20) :2511-2523

[7]

Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile function in the anesthetized dog [J].

Carter, AJ ;

Ballard, SA ;

Naylor, AM .

JOURNAL OF UROLOGY, 1998, 160 (01) :242-246

[8]

DOHERTY PC, 2000, Patent No. 6037346

[9]

DYKES GJ, 2008, Patent No. 20080242661

[10]

Synthesis and properties of isoViagra [1].: A 2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-one isomer of Viagra® [J].

El-Abadelah, MM ;

Sabri, SS ;

Khanfar, MA ;

Yasin, HA ;

Voelter, W .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2002, 39 (05) :1055-1059

← 1 2 3 →