Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors
| Autor: | Timothy M. Caldwell, Michael D. Kaufman, Scott C. Wise, Yu Mi Ahn, Molly M. Hood, Wei-Ping Lu, William C. Patt, Thiwanka Samarakoon, Lakshminarayana Vogeti, Subha Vogeti, Karen M. Yates, Stacie L. Bulfer, Bertrand Le Bourdonnec, Bryan Smith, Daniel Flynn |
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| Rok vydání: | 2022 |
| Předmět: |
History
Polymers and Plastics Organic Chemistry Clinical Biochemistry Pharmaceutical Science Receptor Protein-Tyrosine Kinases Biochemistry Industrial and Manufacturing Engineering Receptor Platelet-Derived Growth Factor beta Structure-Activity Relationship Drug Design Drug Discovery Molecular Medicine Urea Business and International Management Molecular Biology Protein Kinase Inhibitors |
| Zdroj: | Bioorganicmedicinal chemistry letters. 74 |
| ISSN: | 1464-3405 |
| Popis: | 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 displaying high selectivity for CSF1R versus the other members of the Type III receptor tyrosine kinase (RTK) family members (KIT, PDGFR-α, PDGFR-β, 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. |
| Databáze: | OpenAIRE |
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