Identification of novel azaindazole CCR1 antagonist clinical candidates

被引：3

作者：

Harcken, Christian ^{[1
]}

Kuzmich, Daniel ^{[1
]}

Cook, Brain ^{[1
]}

Mao, Can ^{[1
]}

Disalvo, Darren ^{[1
]}

Razavi, Hossein ^{[1
]}

Swinamer, Alan ^{[1
]}

Liu, Pingrong ^{[1
]}

Zhang, Qiang ^{[1
]}

Kukulka, Alison ^{[2
]}

Skow, Donna ^{[2
]}

Patel, Mita ^{[3
]}

Patel, Monica ^{[3
]}

Fletcher, Kimberly ^{[3
]}

Sherry, Tara ^{[3
]}

Joseph, David ^{[3
]}

Smith, Dustin ^{[3
]}

Canfield, Melissa ^{[4
]}

Souza, Donald ^{[4
]}

Bogdanffy, Matthew ^{[5
]}

Berg, Karen ^{[4
]}

Brown, Maryanne ^{[4
]}

机构：

[1] Boehringer Ingelhe Pharmaceut Inc, Med Chem Dept, 900 Ridgebury Rd,POB 368, Ridgefield, CT 06877 USA

[2] Boehringer Ingelhe Pharmaceut Inc, Compound Profiling Dept, 900 Ridgebury Rd,POB 368, Ridgefield, CT 06877 USA

[3] Boehringer Ingelhe Pharmaceut Inc, Drug Discovery Support Dept, 900 Ridgebury Rd,POB 368, Ridgefield, CT 06877 USA

[4] Boehringer Ingelhe Pharmaceut Inc, Immunol & Resp Dis Res Dept, 900 Ridgebury Rd,POB 368, Ridgefield, CT 06877 USA

[5] Boehringer Ingelhe Pharmaceut Inc, Nonclin Drug Safety Dept, 900 Ridgebury Rd,POB 368, Ridgefield, CT 06877 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 03期

关键词：

Chemokine receptors; CCR1; Indazole; Scaffold hopping; Clinical compound; CHEMOKINE RECEPTORS; PLUS METHOTREXATE; ARTHRITIS; EFFICACY; PHARMACOKINETICS; DISCOVERY; BLOCKADE; TARGETS; MLN3897; SAFETY;

D O I：

10.1016/j.bmcl.2018.12.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Exploring various cyclization strategies, using a submicromolar pyrazole HTS screening hit 6 as a starting point, a novel indazole based CCR1 antagonist core was discovered. This report presents the design and SAR of CCR1 indazole and azaindazole antagonists leading to the identification of three development compounds, including 19e that was advanced to early clinical trials.

引用

页码：441 / 448

页数：8

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