1,4-Dihydroindeno[1,2-c]pyrazoles as potent checkpoint kinase I inhibitors:: Extended explorationon phenyl ring substitutions and preliminary ADME/PK studies

被引：12

作者：

Tong, Yunsong ^{[1
]}

Claiborne, Akiyo ^{[1
]}

Pyzytulinska, Magdalena ^{[1
]}

Tao, Zhi-Fu ^{[1
]}

Stewart, Kent D. ^{[1
]}

Kovar, Peter ^{[1
]}

Chen, Zehan ^{[1
]}

Credo, Robert B. ^{[1
]}

Guan, Ran ^{[1
]}

Merta, Philip J. ^{[1
]}

Zhang, Halying ^{[1
]}

Bouska, Jennifer ^{[1
]}

Everitt, Elizabeth A. ^{[1
]}

Murry, Bernard P. ^{[1
]}

Hickman, Dean ^{[1
]}

Stratton, Tim J. ^{[1
]}

Wu, Jian ^{[1
]}

Rosenberg, Saul H. ^{[1
]}

Sham, Hing L. ^{[1
]}

Sowin, Thomas J. ^{[1
]}

Lin, Nan-Horng ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut R&D, Canc Res, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 13期

关键词：

D O I：

10.1016/j.bmcl.2007.04.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A study on substitutions at the four open positions on the phenyl ring of the 1,4-dihydroindeno[1,2-c]pyrazoles as potent CHK-1 inhibitors is described. Bis-substitution at both the 6- and 7-positions led to inhibitors with IC50 values below 0.3 nM. The compound with the best overall activities (36) was able to potentiate the anti-proliferative effect of doxorubicin in HeLa cells by at least 47-fold. Physicochemical, metabolic, and pharmacokinetic properties of selected inhibitors are also disclosed. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3618 / 3623

页数：6

共 16 条

[1] Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors
Tong, Yunsong
Claiborne, Akiyo
Stewart, Kent D.
Park, Chang
Kovar, Peter
Chen, Zehan
Credo, Robert B.
Gu, Wen-Zhen
Gwaltney, Stephen L., II
Judge, Russell A.
Zhang, Haiying
Rosenberg, Saul H.
Sham, Hing L.
Sowin, Thomas J.
Lin, Nan-horng
BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (07) : 2759 - 2767
[2] Cyanopyridyl containing 1,4-dihydroindeno[1,2-c]pyrazoles as potent checkpoint kinase 1 inhibitors: Improving oral biovailability
Tong, Yunsong
Przytulinska, Magdalena
Tao, Zhi-Fu
Bouska, Jennifer
Stewart, Kent D.
Park, Chang
Li, Gaoquan
Claiborne, Akiyo
Kovar, Peter
Chen, Zehan
Merta, Philip J.
Bui, Mai-Ha
Olson, Amanda
Osterling, Donald
Zhang, Haiying
Sham, Hing L.
Rosenberg, Saul H.
Sowin, Thomas J.
Lin, Nan-Horng
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (20) : 5665 - 5670
[3] 1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors
Dinges, Jurgen
Ashworth, Kimba L.
Akritopolou-Zanze, Irini
Arnold, Lee D.
Baumeister, Steven A.
Bousquet, Peter F.
Cunha, George A.
Davidsen, Steven K.
Djuric, Stevan W.
Gracias, Vijaya J.
Michaelides, Michael R.
Rafferty, Paul
Sowin, Thomas J.
Stewart, Kent D.
Xia, Zhiren
Zhang, Henry Q.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) : 4266 - 4271
[4] Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors
Dinges, Jurgen
Akritopoulou-Zanze, Irini
Arnold, Lee D.
Barlozzari, Teresa
Bousquet, Peter F.
Cunha, George A.
Ericsson, Anna M.
Iwasaki, Nobuhiko
Michaelides, Michael R.
Ogawa, Nobuo
Phelan, Kathleen M.
Rafferty, Paul
Sowin, Thomas J.
Stewart, Kent D.
Tokuyama, Ryukou
Xia, Zhiren
Zhang, Henry Q.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) : 4371 - 4375
[5] Synthesis and biological evaluation of 5-substituted 1,4-dihydroindeno[1,2-c]pyrazoles as multitargeted receptor tyrosine kinase inhibitors
Akritopoulou-Zanze, Irim
Albert, Daniel H.
Bousquet, Peter F.
Cunha, George A.
Harris, Christopher M.
Moskey, Maria
Dinges, Jurgen
Stewart, Kent D.
Sowin, Thomas J.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (11) : 3136 - 3140
[6] 1,4-Dihydroindeno[1,2-c] pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors (vol 16, pg 4266, 2006)
Dinges, Juergen
Ashworth, Kimba L.
Akritopoulou-Zanze, Irini
Arnold, Lee D.
Baumeister, Steven A.
Bousquet, Peter F.
Cunha, George A.
Davidsen, Steven K.
Djuric, Stevan W.
Gracias, Vijaya J.
Michaelides, Michael R.
Rafferty, Paul
Sowin, Thomas J.
Stewart, Kent D.
Xia, Zhiren
Zhang, Henry Q.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (12) : 3516 - 3516
[7] SAR Investigation and Discovery of Water-Soluble 1-Methyl-1,4-dihydroindeno[1,2-c]pyrazoles as Potent Tubulin Polymerization Inhibitors
Cui, Ying-Jie
Liu, Chao
Ma, Chen-Chen
Ji, Ya-Ting
Yao, Yi-Li
Tang, Long-Qian
Zhang, Cheng-Mei
Wu, Jing-De
Liu, Zhao-Peng
JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (23) : 14840 - 14866
[8] 1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel
Dinges, Jurgen
Albert, Daniel H.
Arnold, Lee D.
Ashworth, Kimba L.
Akritopoulou-Zanze, Irini
Bousquet, Peter F.
Bouska, Jennifer J.
Cunha, George A.
Davidsen, Steven K.
Diaz, Gilbert J.
Djuric, Stevan W.
Gasiecki, Alan F.
Gintant, Gary A.
Gracias, Vijaya J.
Harris, Christopher M.
Houseman, Kathryn A.
Hutchins, Charles W.
Johnson, Eric F.
Li, Hu
Marcotte, Patrick A.
Martin, Ruth L.
Michaelides, Michael R.
Nyein, Michelle
Sowin, Thomas J.
Su, Zhi
Tapang, Paul H.
Xia, Zhiren
Zhang, Henry Q.
JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (09) : 2011 - 2029
[9] Combined 3D-QSAR modeling and molecular docking study on 1,4-dihydroindeno[1,2-c]pyrazoles as VEGFR-2 kinase inhibitors
Zeng, Huahui
Zhang, Huabei
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2010, 29 (01): : 54 - 71
[10] Design, synthesis, in silico pharmacokinetics prediction and biological evaluation of 1,4-dihydroindeno[1,2-c]pyrazole chalcone as EGFR/Akt pathway inhibitors
Khan, Irfan
Garikapati, Koteswara Rao
Setti, Aravind
Shaik, Anver Basha
Makani, Venkata Krishna Kanth
Shareef, Mohd Adil
Rajpurohit, Hemshikha
Vangara, Namratha
Pal-Bhadra, Manika
Kamal, Ahmed
Kumar, C. Ganesh
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 163 : 636 - 648

← 1 2 →