Synthesis and biological evaluation of 3-(4-fluorophenyl)-1H-pyrazole derivatives as androgen receptor antagonists

被引：9

作者：

Guo, Guangzhu ^{[1
]}

Liu, Jianzhen ^{[1
]}

Wang, Guanjie ^{[1
]}

Zhang, Daoguang ^{[1
]}

Lu, Jinjie ^{[1
]}

Zhao, Guisen ^{[1
]}

机构：

[1] Shandong Univ, Key Lab Chem Biol, Minist Educ, Sch Pharmaceut Sci,Dept Med Chem, Jinan 250012, Shandong, Peoples R China

来源：

ANTI-CANCER DRUGS | 2016年 / 27卷 / 04期

基金：

中国国家自然科学基金;

关键词：

antagonist; pyrazole derivatives; androgen receptor; prostate cancer; RESISTANT PROSTATE-CANCER; BINDING POCKET; DESIGN;

D O I：

10.1097/CAD.0000000000000322

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A novel series of 3-(4-fluorophenyl)-1H-pyrazole derivatives were synthesized and evaluated for their antiproliferative activity against two prostate cancer cell lines (LNCaP and PC-3) and androgen receptor target gene prostate-specific antigen (PSA) inhibitory activity in LNCaP cells. Several compounds showed potent antiproliferative activity against LNCaP cells and showed a promising PSA downregulation rate. Among these, compound 10e selectively inhibited LNCaP cell growth with an IC50 value of 18 mu mol/l and showed a PSA downregulation rate of 46%, which was better than the lead compound T3.

引用

页码：278 / 285

页数：8

共 8 条

[1] Advances in Androgen Receptor Targeted Therapy for Prostate Cancer
Ahmed, Alia
Ali, Shadan
Sarkar, Fazlul H.
[J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2014, 229 (03) : 271 - 276
[2] First-in-human Phase I study of EZN-4176, a locked nucleic acid antisense oligonucleotide to exon 4 of the androgen receptor mRNA in patients with castration-resistant prostate cancer
Bianchini, D.
Omlin, A.
Pezaro, C.
Lorente, D.
Ferraldeschi, R.
Mukherji, D.
Crespo, M.
Figueiredo, I.
Miranda, S.
Riisnaes, R.
Zivi, A.
Buchbinder, A.
Rathkopf, D. E.
Attard, G.
Scher, H. I.
de Bono, J.
Danila, D. C.
[J]. BRITISH JOURNAL OF CANCER, 2013, 109 (10) : 2579 - 2586
[3] "True" Antiandrogens-Selective Non-Ligand-Binding Pocket Disruptors of Androgen Receptor-Coactivator Interactions: Novel Tools for Prostate Cancer
Caboni, Laura
Kinsella, Gemma K.
Blanco, Fernando
Fayne, Darren
Jagoe, William N.
Carr, Miriam
Williams, D. Clive
Meegan, Mary J.
Lloyd, David G.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (04) : 1635 - 1644
[4] Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists derived from 1,2-dihydropyridino[5,6-g]quinolines
Hamann, LG
Higuchi, RI
Zhi, L
Edwards, JP
Wang, XN
Marschke, KB
Kong, JW
Farmer, LJ
Jones, TK
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (04) : 623 - 639
[5] Discovery of novel androgen receptor antagonists: a hybrid approach of pharmacophore-based and docking-based virtual screening
Liu, Jianzhen
Liu, Bo
Guo, Guangzhu
Jing, Yongkui
Zhao, Guisen
[J]. ANTI-CANCER DRUGS, 2015, 26 (07) : 747 - 753
[6] Development of Androgen Receptor Antagonists with Promising Activity in Castration-Resistant Prostate Cancer
Shen, Howard C.
Balk, Steven P.
[J]. CANCER CELL, 2009, 15 (06) : 461 - 463
[7] Progress in antiandrogen design targeting hormone binding pocket to circumvent mutation based resistance
Tian, Xiaohong
He, Yang
Zhou, Jinming
[J]. FRONTIERS IN PHARMACOLOGY, 2015, 6
[8] Design and Synthesis of Androgen Receptor Antagonists with Bulky Side Chains for Overcoming Antiandrogen Resistance
Zhou, Jinming
Geng, Guoyan
Shi, Qingwen
Sauriol, Francoise
Wu, Jian Hui
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (17) : 5546 - 5550

← 1 →