2,4-Diamino-quinazolines as inhibitors of β-catenin/Tcf-4 pathway: Potential treatment for colorectal cancer

被引：63

作者：

Chen, Zecheng ^{[1
]}

Venkatesan, Aranapakam M. ^{[1
]}

Dehnhardt, Christoph M. ^{[1
]}

Dos Santos, Osvaldo ^{[1
]}

Delos Santos, Efren ^{[1
]}

Ayral-Kaloustian, Semiramis ^{[1
]}

Chen, Lei ^{[2
]}

Geng, Yi ^{[2
]}

Arndt, Kim T. ^{[2
]}

Lucas, Judy ^{[2
]}

Chaudhary, Inder ^{[3
]}

Mansour, Tarek S. ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Oncol, Pearl River, NY 10965 USA

[3] Wyeth Res, Drug Metab, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

beta-Catenin/Tcf-4; pathway; Inhibitors; 2,4-Diamino-quinazoline; WNT; AXIN2; APC;

D O I：

10.1016/j.bmcl.2009.07.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and SAR of a series of 2,4-diamino-quinazoline derivatives as beta-catenin/Tcf-4 inhibitors are described. This series was developed by modifying the initial lead 1, which was identified by screening of our compound library and found to inhibit the beta-catenin/Tcf-4 pathway. Replacement of the biphenyl moiety in compound 1 with the N-phenylpiperidine-4-carboxamide chain as in 2, resulted in a number of new analogues, which are potent inhibitors of the beta-catenin/Tcf-4 pathway. Compound such as 16k exhibited good cellular potency, solubility, metabolic stability and oral bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4980 / 4983

页数：4

共 39 条

[21] Retinoic Acid-Induced 2 (RAI2) Is a Novel Antagonist of Wnt/β-Catenin Signaling Pathway and Potential Biomarker of Chemosensitivity in Colorectal Cancer
Zhang, Weitao
Kong, Lu
Zhu, Hongbin
Sun, Decong
Han, Quanli
Yan, Bin
Cui, Zhi
Zhang, Weiwei
Zhang, Shurong
Kang, Xindan
Dai, Guanghai
Qian, Niansong
Yan, Wenji
FRONTIERS IN ONCOLOGY, 2022, 12
[22] S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway (Jun, 10.1007/s11626-024-00930-2, 2024)
Zhou, Jin
Murata, Hitoshi
Tomonobu, Nahoko
Mizuta, Naoko
Yamakawa, Atsuko
Yamamoto, Ken-ichi
Kinoshita, Rie
Sakaguchi, Masakiyo
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2024, 60 (10) : 1150 - 1150
[23] Inhibition of ErbB2 by Herceptin reduces survivin expression via the ErbB2-β-catenin/TCF4-survivin pathway in ErbB2-overexpressed breast cancer cells
Zhu, Hongxia
Zhang, Guo
Wang, Yan
Xu, Ninghong
He, Shun
Zhang, Wei
Chen, Meigui
Liu, Mei
Quan, Lanping
Bai, Jingfeng
Xu, Ningzhi
CANCER SCIENCE, 2010, 101 (05): : 1156 - 1162
[24] Design, synthesis and activity evaluation of isopropylsulfonyl-substituted 2,4-diarylaminopyrimidine derivatives as FAK inhibitors for the potential treatment of pancreatic cancer
Zheng, Xu
Li, Xing
Tian, Liangliang
Wu, Bin
Yu, Jiawen
Wang, Changyuan
Sun, Xiuli
Ma, Xiaodong
Chen, Lixue
Li, Yanxia
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2022, 241
[25] Discovery of Substituted 2-oxoquinolinylthiazolidin-4-one Analogues as Potential EGFRK Inhibitors in Lung Cancer Treatment
Naik, Soniya
Soumya, Vasu
Mamledesai, Shivlingrao N.
Manickavasagam, M.
Choudhari, Prafulla
Rathod, Sanket
DRUG RESEARCH, 2024, 74 (05) : 227 - 240
[26] Resveratrol induces the growth inhibition of CDX-deficient gastric cancer cells using CDX2 and RUNX3 via the β-catenin/TCF4 signaling pathway
Liu, Hui
Zhang, Xinxin
Fang, Can
Li, Shuguang
TRANSLATIONAL ONCOLOGY, 2023, 35
[27] Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: Identification and optimisation of substituted 2,4-bis anilino pyrimidines
Breault, GA
Ellston, RPA
Green, S
James, SR
Jewsbury, PJ
Midgley, CJ
Pauptit, RA
Minshull, CA
Tucker, JA
Pease, JE
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (18) : 2961 - 2966
[28] Tumor-suppressive miR-145 co-repressed by TCF4-β-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer
Wang, Wei
Xiao, Xin
Chen, Xu
Huo, Yi
Xi, Wen-Jin
Lin, Zhi-Feng
Zhang, Dan
Li, Yu-Fang
Yang, Fan
Wen, Wei-Hong
Yang, An-Gang
Wang, Tao
INTERNATIONAL JOURNAL OF CANCER, 2018, 142 (02) : 308 - 321
[29] Design, synthesis, and biological evaluation of 1,6-naphthyridine-2-one derivatives as novel FGFR4 inhibitors for the treatment of colorectal cancer
Fang, Bo
Lai, Yinshuang
Yan, Hao
Ma, Yue
Ni, Zefeng
Zhu, Qianqian
Zhang, Jianxia
Ye, Yanfei
Wang, Mengying
Wang, Peipei
Wang, Yan
Zhang, Shuyuan
Hui, Min
Wang, Dalong
Zhao, Yunjie
Li, Xiaokun
Wang, Kun
Liu, Zhiguo
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 259
[30] CircRASSF2 facilitates the proliferation and metastasis of colorectal cancer by mediating the activity of Wnt/β-catenin signaling pathway by regulating the miR-195-5p/FZD4 axis
Yang, Leilei
Bi, Tienan
Zhou, Shenkang
Lan, Yuefu
Zhang, Ruili
ANTI-CANCER DRUGS, 2021, 32 (09) : 919 - 929

← 1 2 3 4 →