Discovery of N-substituted 7-azaindoles as Pan-PIM kinase inhibitors - Lead series identification - Part II

被引：4

作者：

Barberis, Claude ^{[1
]}

Moorcroft, Neil ^{[1
,6
]}

Pribish, James ^{[1
]}

Tserlin, Elina ^{[1
]}

Gross, Alexandre ^{[1
]}

Czekaj, Mark ^{[1
]}

Barrague, Matthieu ^{[1
]}

Erdman, Paul ^{[1
]}

Majid, Tahir ^{[1
]}

Batchelor, Joseph ^{[5
]}

Levit, Mikhail ^{[2
]}

Hebert, Andrew ^{[2
]}

Shen, Liduo ^{[4
]}

Moreno-Mazza, Sandra ^{[3
]}

Wang, Anlai ^{[2
]}

机构：

[1] Sanofi Genzyme, IDD Med Chem, 153 Second Ave, Waltham, MA 02451 USA

[2] Sanofi, Oncol Biol, 270 Albany St, Cambridge, MA 02139 USA

[3] Sanofi, Oncol Biochem, 270 Albany St, Cambridge, MA 02139 USA

[4] Sanofi Genzyme, DSAR, 211 Second Ave, Waltham, MA 02451 USA

[5] Sanofi, IDD Vitro Biol, 153 Second Ave, Waltham, MA 02451 USA

[6] Maxsar Biopharma, 18 Roberts Rd, Warren, NJ 07059 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 20期

关键词：

Pan-PIM kinases; X-ray crystallography; AML; PK/PD; Hit-to-Lead; Small molecule inhibitor; Cancer; SELECTIVE INHIBITORS; POTENT; PROTEIN; DERIVATIVES; EXPRESSION; BINDING; HIT; BAD; OPTIMIZATION; ACTIVATION;

D O I：

10.1016/j.bmcl.2017.08.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-Substituted azaindoles have been discovered as pan-PIM kinase inhibitors. Initial SAR, early ADME and PK/PD data of a series of compounds is described and led to the identification of promising pan-PIM inhibitors which validated our interest in the 7-azaindole scaffold and led us to pursue the identification of a clinical candidate. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：4735 / 4740

页数：6

共 16 条

[1] Discovery of N-substituted 7-azaindoles as Pan-PIM kinases inhibitors - Lead optimization - Part III
Barberis, Claude
Pribish, James
Tserlin, Elina
Gross, Alexandre
Czekaj, Mark
Barrague, Matthieu
Erdman, Paul
Maniar, Sachin
Jiang, John
Fire, Luke
Patel, Vinod
Hebert, Andrew
Levit, Mikhail
Wang, Anlai
Sun, Frank
Huang, Shih-Min A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (03) : 491 - 495
[2] Discovery of N-substituted 7-azaindoles as PIM1 kinase inhibitors - Part I
Barberis, Claude
Moorcroft, Neil
Arendt, Chris
Levit, Mikhail
Moreno-Mazza, Sandra
Batchelor, Joseph
Mechin, Ingrid
Majid, Tahir
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (20) : 4730 - 4734
[3] Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (Part-II)
Sessions, E. Hampton
Chowdhury, Sarwat
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[4] Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors
Hu, Huiyong
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[5] Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors
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[6] The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors
Wang, Hui-Ling
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Chavez, Frank, Jr.
Lanman, Brian A.
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Wu, Bin
Guerrero, Nadia
Lipford, J. Russell
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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (04) : 834 - 840
[7] Discovery of a Series of 7-Azaindoles as Potent and Highly Selective CDK9 Inhibitors for Transient Target Engagement
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Wu, Liangwei
Xue, Lin
Yang, Bin
Yao, Tieguang
JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (20) : 15189 - 15213
[8] N-substituted 2′-(aminoaryl)benzothiazoles as kinase inhibitors: Hit identification and scaffold hopping
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Mueller, Oliver
Wieber, Tanja
Herz, Thomas
Krauss, Rolf
Totzke, Frank
Kubbutat, Michael H. G.
Schaechtele, Christoph
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (05) : 1349 - 1356
[9] Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402
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JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (02) : 798 - 810
[10] Amide-based inhibitors of p38α MAP kinase. Part 1: Discovery of novel N-pyridyl amide lead molecules
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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (08) : 2556 - 2559

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