Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases

被引：68

作者：

Claridge, Stephen ^{[1
]}

Raeppel, Franck ^{[1
]}

Granger, Marie-Claude ^{[1
]}

Bernstein, Naomy ^{[1
]}

Saavedra, Oscar ^{[1
]}

Zhan, Lijie ^{[1
]}

Llewellyn, David ^{[1
]}

Wahhab, Amal ^{[1
]}

Deziel, Robert ^{[1
]}

Rahil, Jubrail ^{[3
]}

Beaulieu, Normand ^{[2
]}

Nguyen, Hannah ^{[2
]}

Dupont, Isabelle ^{[2
]}

Barsalou, Annie ^{[2
]}

Beaulieu, Carole ^{[2
]}

Chute, Ian ^{[2
]}

Gravel, Serge ^{[2
]}

Robert, Marie-France ^{[2
]}

Lefebvre, Sylvain ^{[2
]}

Dubay, Marja ^{[2
]}

Pascal, Roussen ^{[4
]}

Gillespie, Jeff ^{[4
]}

Jin, Zhiyun ^{[4
]}

Wang, James ^{[4
]}

Besterman, Jeffrey M. ^{[2
]}

MacLeod, A. Robert ^{[2
]}

Vaisburg, Arkadii ^{[1
]}

机构：

[1] MethylGene Inc, Dept Med Chem, Montreal, PQ H4S 2A1, Canada

[2] MethylGene Inc, Dept Cell Biol & Pharmacol, Montreal, PQ H4S 2A1, Canada

[3] MethylGene Inc, Dept Lead Discovery, Montreal, PQ H4S 2A1, Canada

[4] MethylGene Inc, Dept PK Analyt Chem, Montreal, PQ H4S 2A1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

c-Met; VEGFR2; kinase; thieno[3,2-b]pyridine; cancer;

D O I：

10.1016/j.bmcl.2008.04.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases is described. The compounds demonstrated potency with IC50 values in the low nanomolar range in vitro while the lead compound also showed in vivo activity against various human tumor xenograft models in mice. Further exploration of this class of compounds is underway. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2793 / 2798

页数：6

共 39 条

[1] N3-Arylmalonamides: A new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases
Saavedra, Oscar
Claridge, Stephen
Zhan, Lijie
Raeppel, Franck
Granger, Marie-Claude
Raeppel, Stephane
Mannion, Michael
Gaudette, Frederic
Zhou, Nancy
Isakovic, Ljubomir
Bernstein, Naomy
Deziel, Robert
Nguyen, Hannah
Beaulieu, Normand
Beaulieu, Carole
Dupont, Isabelle
Wang, James
Macleod, A. Robert
Besterman, Jeffrey M.
Vaisburg, Arkadii
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (24) : 6836 - 6839
[2] Discovery of a novel and potent, and urea isostere inhibitors series of dianilinopyrimidineurea of VEGFR2 tyrosine kinase
Sammond, DM
Nallor, KE
Veal, JM
Nolte, RT
Wang, LP
Knick, VB
Rudolph, SK
Truesdale, AT
Nartey, EN
Stafford, JA
Kumar, R
Cheung, M
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (15) : 3519 - 3523
[3] Structure-based design, synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors
Matsumoto, Shigemitsu
Miyamoto, Naoki
Hirayama, Takaharu
Oki, Hideyuki
Okada, Kengo
Tawada, Michiko
Iwata, Hidehisa
Nakamura, Kazuhide
Yamasaki, Seiji
Miki, Hiroshi
Hori, Akira
Imamura, Shinichi
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (24) : 7686 - 7698
[4] N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors
Raeppel, Stephane
Claridge, Stephen
Saavedra, Oscar
Gaudette, Frederic
Zhan, Lijie
Mannion, Michael
Zhou, Nancy
Raeppel, Franck
Granger, Marie-Claude
Isakovic, Ljubomir
Deziel, Robert
Nguyen, Hannah
Beaulieu, Normand
Beaulieu, Carole
Dupont, Isabelle
Robert, Marie-France
Lefebvre, Sylvain
Dubay, Marja
Rahil, Jubrail
Wang, James
Ste-Croix, Helene
Macleod, A. Robert
Besterman, Jeffrey
Vaisburg, Arkadii
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (05) : 1323 - 1328
[5] Structure activity relationships of chrysoeriol and analogs as dual c-Met and VEGFR2 tyrosine kinase inhibitors
Lai, Shuang
Chen, Jun-Ning
Huang, Han-Wei
Zhang, Xiang-Yu
Jiang, Hai-Lun
Li, Wei
Wang, Peng-Liang
Wang, Jian
Liu, Fu-Nan
ONCOLOGY REPORTS, 2018, 40 (03) : 1650 - 1656
[6] Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors
Gu, Weijie
Dai, Yuxuan
Qiang, Hao
Shi, Wei
Liao, Chen
Zhao, Fangnuo
Huang, Wenlong
Qian, Hai
BIOORGANIC CHEMISTRY, 2017, 72 : 116 - 122
[7] Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors
Li, Jieming
Gu, Weijie
Bi, Xinzhou
Li, Huilan
Liao, Chen
Liu, Chunxia
Huang, Wenlong
Qian, Hai
BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (24) : 6674 - 6679
[8] Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization
An, Xiao-De
Liu, Hongyan
Xu, Zhong-Liang
Jin, Yi
Peng, Xia
Yao, Ying-Ming
Geng, Meiyu
Long, Ya-Qiu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (03) : 708 - 716
[9] The Discovery of furo[2,3-c]pyridine-based indanone oximes as potent and selective B-Raf inhibitors
Buckmelter, Alex J.
Ren, Li
Laird, Ellen R.
Rast, Bryson
Miknis, Greg
Wenglowsky, Steve
Schlachter, Stephen
Welch, Mike
Tarlton, Eugene
Grina, Jonas
Lyssikatos, Joseph
Brandhuber, Barbara J.
Morales, Tony
Randolph, Nikole
Vigers, Guy
Martinson, Matthew
Callejo, Michele
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (04) : 1248 - 1252
[10] Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors
Zhang, Dengyou
Ai, Jing
Liang, Zhongjie
Li, Chunpu
Peng, Xia
Ji, YinChun
Jiang, Hualiang
Geng, Meiyu
Luo, Cheng
Liu, Hong
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (17) : 5169 - 5180

← 1 2 3 4 →