Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as human scavenger receptor CD36 antagonists. 2011

Yan-Xiang Wang, and Li Wang, and Yan-Ni Xu, and Ying-Hong Li, and Jian-Dong Jiang, and Shu-Yi Si, and Yang-Biao Li, and Gang Ren, and Yong-Qiang Shan, and Bin Hong, and Dan-Qing Song
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

By using human scavenger receptor CD36 as the target, twenty-five N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their antagonistic activities for CD36-oxidatively low density lipoprotein (oxLDL) binding. The primary analysis of structure-activity relationship (SAR) indicated a methoxyl at the 7-position and a hydroxyl at the 6- or 8-position could afford good activities. Among these analogs, compounds 7e and 7t showed the potential CD36 antagonistic activities with IC(50) values of 0.2 and 0.8 μg/mL, respectively. Furthermore, both of them could effectively inhibit oxLDL uptake in insect Sf9 cells overexpressing human CD36, and thus have been selected for further investigation. We consider N-(2-arylethyl) isoquinoline analogs to be a family of novel CD36 antagonists.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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
D018955 CD36 Antigens Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS. Antigens, CD36,OKM5 Antigen,Platelet Glycoprotein IV,Platelet Membrane Glycoprotein IIIb,Receptors, Thrombospondin,Scavenger Receptors, Class B, Type I,Thrombospondin Receptors,Adipocyte Membrane Protein p88,CD36 Antigen,CD36 Antigen (Collagen Type I Receptor, Thrombospondin Receptor),CD36 Fatty Acid Transporter,CD36 Protein,FAT (Fatty Acid Translocase) - CD36 Antigen,GPIIIb Platelet Glycoprotein,GPIV Platelet Glycoprotein,Platelet Glycoprotein IIIb,Platelet Membrane Glycoprotein IV,SR-BI Protein,SR-BI Receptor,Thrombospondin Receptor,Antigen, CD36,Antigen, OKM5,Glycoprotein IIIb, Platelet,Glycoprotein IV, Platelet,Platelet Glycoprotein, GPIIIb,Platelet Glycoprotein, GPIV,Receptor, SR-BI,Receptor, Thrombospondin,SR BI Protein,SR BI Receptor

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