BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors. 2023

Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, China.

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within.

UI MeSH Term Description Entries
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases

Related Publications

Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, synthesis, biological evaluation, and in silico studies of 2-aminobenzothiazole derivatives as potent PI3Kα inhibitors.
October 2022, Archiv der Pharmazie,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, synthesis and biological evaluation of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as potential dual PI3Kα/mTOR inhibitors.
January 2020, Bioorganic chemistry,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors.
September 2019, Molecules (Basel, Switzerland),
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, synthesis and biological evaluation of imidazopyridine-propenone conjugates as potent tubulin inhibitors.
May 2017, MedChemComm,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors.
January 2022, Molecules (Basel, Switzerland),
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, Synthesis, and Pharmacological Evaluation of Novel N-Acylhydrazone Derivatives as Potent Histone Deacetylase 6/8 Dual Inhibitors.
January 2016, Journal of medicinal chemistry,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors.
November 2007, Bioorganic & medicinal chemistry letters,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, synthesis and biological evaluation of 2-aminopyrimidine derivatives as potent FLT3 inhibitors.
November 2023, Bioorganic & medicinal chemistry letters,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Computer-aided design, synthesis, and biological evaluation of new indole-2-carboxamide derivatives as PI3Kα/EGFR inhibitors.
June 2016, Bioorganic & medicinal chemistry letters,
Rui Chen, and Zhongyuan Wang, and Lijie Sima, and Hu Cheng, and Bilan Luo, and Jianta Wang, and Bing Guo, and Shunyi Mao, and Zhixu Zhou, and Jingang Peng, and Lei Tang, and Xinfu Liu, and Weike Liao
Design, synthesis and biological evaluation of novel substituted benzoylguanidine derivatives as potent Na+/H+ exchanger inhibitors.
June 2009, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!