Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I)

Autor: Liang-Shang Gan, Betty Tam, Khang Vu, Jinhua Piao, Douglas Marcotte, Shuo Zhao, Min Teng, Jianhua Chao, Charles A. Iii Gilson, Dikran Aivazian, Qin Wang, Guangqing Xiao, Arthur G. Taveras, Samina Khan, Tony Li, Junhua Fan, Jean-Yves Le Brazidec, Wen-Cherng Lee, Noel Timple, Khanh Nguyen, Lin Zhang, Jer-Hong Chong, Kevin Hong, Laura Silvian, Nicole Takeda, Mitchell Reff, Angela Cesena, Ron A. Morena, Deping Wang, Karen Lundgren, Leona E. Ling, Christina Boykin
Rok vydání: 2011
Předmět:
Models
Molecular
Clinical Biochemistry
Pharmaceutical Science
Mice
Nude
Antineoplastic Agents
Chemistry Techniques
Synthetic
Mitogen-activated protein kinase kinase
Protein Serine-Threonine Kinases
Crystallography
X-Ray
Biochemistry
Pyrazolopyrimidine
chemistry.chemical_compound
Mice
Structure-Activity Relationship
Aurora Kinases
Cell Line
Tumor
Drug Discovery
CDC2 Protein Kinase
Animals
Humans
Molecular Biology
Protein Kinase Inhibitors
Aurora Kinase A
Cell Proliferation
Cyclin-dependent kinase 1
Sulfonamides
biology
Dose-Response Relationship
Drug
Molecular Structure
Cyclin-dependent kinase 4
Chemistry
Organic Chemistry
Cyclin-dependent kinase 2
Stereoisomerism
Neoplasms
Experimental
Protein kinase R
Xenograft Model Antitumor Assays
Ether-A-Go-Go Potassium Channels
Pyrimidines
Drug Design
Colonic Neoplasms
biology.protein
Cancer research
Molecular Medicine
Cyclin-dependent kinase 9
biological phenomena
cell phenomena
and immunity
Zdroj: Bioorganicmedicinal chemistry letters. 21(18)
ISSN: 1464-3405
Popis: A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC50s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model.
Databáze: OpenAIRE
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