Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold.
نویسندگان
چکیده
A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57-16 μM.
منابع مشابه
Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.
A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC(50) of 0.022 μM was identified. The compound exhibited dose-de...
متن کاملDesigning and Synthesis of Novel Celecoxib Derivatives with Aminosulfonylmethyl and Azidomethyl Substituents as Selective Cyclooxygenase-2 Inhibitors
Introduction: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are used in treating pathologic conditions such as fever, pain and inflammation by inhibiting cyclooxygenase and consequently prostaglandin production. Recently , the discovery of different isoforms of this enzyme, Cyclooxygenase-1 (COX-1) and Cyclooxygense-2 (COX-2), has led to the synthesis and introduction of novel drugs with selec...
متن کاملDesigning and Synthesis of Novel Celecoxib Derivatives with Aminosulfonylmethyl and Azidomethyl Substituents as Selective Cyclooxygenase-2 Inhibitors
Introduction: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are used in treating pathologic conditions such as fever, pain and inflammation by inhibiting cyclooxygenase and consequently prostaglandin production. Recently , the discovery of different isoforms of this enzyme, Cyclooxygenase-1 (COX-1) andCyclooxygense-2 (COX-2), has led to the synthesis and introduction of novel drugs with select...
متن کاملStructural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family.
Recently, a novel family of methyltransferases was identified in plants. Some members of this newly discovered and recently characterized methyltransferase family catalyze the formation of small-molecule methyl esters using S-adenosyl-L-Met (SAM) as a methyl donor and carboxylic acid-bearing substrates as methyl acceptors. These enzymes include SAMT (SAM:salicylic acid carboxyl methyltransferas...
متن کاملDiscovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups.
Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N¹-(3-fluoro-4-methoxyphenyl)-N³-(4-fluorophenyl) malonamide derivatives were designed and synthesiz...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Molecules
دوره 19 2 شماره
صفحات -
تاریخ انتشار 2014