Design and synthesis of a novel series of N,4-diphenylpyrimidin-2-amine derivatives as potent and selective PI3Kγ inhibitors
| Autor: | Chang-Po Zhao, Hai-Liang Zhu, Jian Sun, Jing-Ran Li, Qian-Ru Du, Hua-Lin Yang, Fei Fang, Dong-Dong Li |
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| Rok vydání: | 2014 |
| Předmět: |
Pharmacology
Drug Chemistry Kinase Stereochemistry media_common.quotation_subject Organic Chemistry Molecular Docking Analysis Pharmaceutical Science Inhibitory postsynaptic potential Biochemistry Combinatorial chemistry In vitro Drug Discovery Molecular Medicine IC50 Human cancer Amine derivatives media_common |
| Zdroj: | Med. Chem. Commun.. 5:219-225 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c3md00301a |
| Popis: | Due to the increasing evidence linking the PI3Kγ pathway to various disease states, PI3Kγ is becoming an important target for cancer treatment. Herein we designed and synthesized a novel series of N,4-diphenylpyrimidin-2-amine derivatives with low CDOCKER_INTERACTION_ENERGY and then evaluated their PI3Kγ in vitro inhibitory activities and in vitro antiproliferation assays against four human cancer cells. Among the compounds we synthesized, compound C8 (IC50 = 65 nM) demonstrated the most potent inhibitory activity against PI3Kγ kinase as well as at the cellular level, compared to the control drug TG100713 (IC50 = 127 nM). Moreover, molecular docking analysis was also performed to determine possible binding modes between PI3Kγ and the target compounds. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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