Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors

被引：6

作者：

Caldwell, Timothy M. ^{[1
]}

Kaufman, Michael D. ^{[1
]}

Wise, Scott C. ^{[1
]}

Ahn, Yu Mi ^{[1
]}

Hood, Molly M. ^{[1
]}

Lu, Wei -Ping ^{[1
]}

Patt, William C. ^{[1
]}

Samarakoon, Thiwanka ^{[1
]}

Vogeti, Lakshminarayana ^{[1
]}

Vogeti, Subha ^{[1
]}

Yates, Karen M. ^{[1
]}

Bulfer, Stacie L. ^{[1
]}

Le Bourdonnec, Bertrand ^{[1
]}

Smith, Bryan D. ^{[1
]}

Flynn, Daniel L. ^{[1
,2
]}

机构：

[1] Deciphera Pharmaceut LLC, Waltham, MA 02451 USA

[2] 643 Massachusetts St,Suite 200, Lawrence, KS 66044 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 74卷

关键词：

CSF1R; Kinase; Acyl ureas; Cancer; TUMOR-ASSOCIATED MACROPHAGES; STIMULATING FACTOR-I; MICROGLIAL PROLIFERATION;

D O I：

10.1016/j.bmcl.2022.128929

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on the structure of an early lead identified in Deciphera's proprietary compound collection of switch control kinase inhibitors and using a combination of medicinal chemistry guided structure activity relationships and structure-based drug design, a novel series of potent acyl urea-based CSF1R inhibitors was identified dis-playing high selectivity for CSF1R versus the other members of the Type III receptor tyrosine kinase (RTK) family members (KIT, PDGFR-alpha, PDGFR-beta, and FLT3), VEGFR2 and MET. Based on in vitro biology, in vitro ADME and in vivo PK/PD studies, compound 10 was selected as an advanced lead for Deciphera's CSF1R research program.

引用

页数：6

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