The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst. The coupling reaction provided generally the para-substituted benzoylpyrazoles in the higher yields than the meta-substituted ones. The Boc groups were only utilized as directing functionalities for the benzoylation step and were hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for elimination of the additional deprotection step.

• Keywords
• Boc-protection, CDK inhibitor, Suzuki-Miyaura reaction, XPhos Pd G2, acylation, pyrazole,
• MeSH
• Acylation MeSH
• Azo Compounds chemistry   MeSH
• Hydrolysis MeSH
• Protein Kinase Inhibitors chemistry   MeSH
• Catalysis MeSH
• Molecular Structure MeSH
• Palladium chemistry   MeSH
• Pyrazoles chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Azo Compounds MeSH
• CAN 508 MeSH Browser
• Protein Kinase Inhibitors MeSH
• Palladium MeSH
• Pyrazoles MeSH

Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in chemical inhibitors with possible therapeutic benefit. While most known inhibitors display broad selectivity towards multiple CDKs, recent work highlights CDK9 as the critical target responsible for the anticancer activity of clinically evaluated drugs. In this review, we discuss recent findings provided by structural biologists that may allow further development of highly specific inhibitors of CDK9 towards applications in cancer therapy. We also highlight the role of CDK9 in inflammatory processes and diseases.

• MeSH
• Cyclin-Dependent Kinase 9 antagonists & inhibitors   metabolism   MeSH
• Protein Kinase Inhibitors pharmacology   MeSH
• Drug Delivery Systems * MeSH
• Humans MeSH
• Neoplasms drug therapy   enzymology   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Drug Design MeSH
• Inflammation enzymology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Cyclin-Dependent Kinase 9 MeSH
• Protein Kinase Inhibitors MeSH
• Antineoplastic Agents MeSH