Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors
| Autor: | Linxiao Wang, Rong Luo, Qidong Tang, Yayi Tu, Ping Gong, Chunjiang Wu, Ping Wang, Pengwu Zheng, Wufu Zhu, Qidong Tu |
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| Rok vydání: | 2016 |
| Předmět: |
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Molecular 1 2 3-Triazole Pyridines Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents 01 natural sciences Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Neoplasms Drug Discovery Pyridine Humans Structure–activity relationship Moiety Pyrroles Protein Kinase Inhibitors Molecular Biology IC50 010405 organic chemistry Kinase Organic Chemistry Proto-Oncogene Proteins c-met Triazoles In vitro 0104 chemical sciences Molecular Docking Simulation chemistry Drug Design 030220 oncology & carcinogenesis Molecular Medicine Drug Screening Assays Antitumor Linker |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:1680-1684 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.02.059 |
| Popis: | A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure-activity relationship studies indicated that electron-withdrawing groups (X=CF3, R(1)=F, R(2)=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity. |
| Databáze: | OpenAIRE |
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