BIOMAT Database Logo BIOMAT Database Logo

Design and Synthesis of A-Ring Simplified Pyripyropene A Analogues as Potent and Selective Synthetic SOAT2 Inhibitors. 2018

Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Department of Synthetic Natural Products Chemistry, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

Currently, pyripyropene A, which is isolated from the culture broth of Aspergillus fumigatus FO-1289, is the only compound known to strongly and selectively inhibit the isozyme sterol O-acyltransferase 2 (SOAT2). To aid in the development of new cholesterol-lowering or anti-atherosclerotic agents, new A-ring simplified pyripyropene A analogues have been designed and synthesized based on total synthesis, and the results of structure-activity relationship studies of pyripyropene A. Among the analogues, two A-ring simplified pyripyropene A analogues exhibited equally efficient SOAT2 inhibitory activity to that of natural pyripyropene A. These new analogues are the most potent and selective SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds for the development of drug for dyslipidemia, including atherosclerotic disease and steatosis.

UI MeSH Term Description Entries
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D002785 Sterol O-Acyltransferase An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26. Acyl-CoA-Cholesterol Acyltransferase,Cholesterol Acyltransferase,Cholesterol Esterifying Enzyme,Acyl CoA Cholesterol Acyltransferase,Acyltransferase, Acyl-CoA-Cholesterol,Acyltransferase, Cholesterol,Enzyme, Cholesterol Esterifying,Esterifying Enzyme, Cholesterol,O-Acyltransferase, Sterol,Sterol O Acyltransferase
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000097587 Sterol O-Acyltransferase 2 A sterol O-acyltransferase that catalyzes reaction of Acyl-CoA and cholesterol into CoA and cholesterol ester. It is a distinct enzyme from Acetyl-CoA C-Acetyltransferase 2, which is also referred to as ACAT2. Acyl-CoA Cholesterol Acyltransferase-2,Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT-2),Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT2),SOAT-2 Protein,SOAT2 Protein
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

Related Publications

Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors.
October 2012, Journal of medicinal chemistry,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors.
November 2002, Bioorganic & medicinal chemistry letters,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Design and synthesis of simple, yet potent and selective non-ring-A pyripyropene A-based inhibitors of acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2).
January 2016, Organic & biomolecular chemistry,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors.
February 2016, Journal of medicinal chemistry,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
New pyripyropene A derivatives, highly SOAT2-selective inhibitors, improve hypercholesterolemia and atherosclerosis in atherogenic mouse models.
November 2015, The Journal of pharmacology and experimental therapeutics,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.
July 2016, ChemMedChem,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Synthesis of proline analogues as potent and selective cathepsin S inhibitors.
June 2013, Bioorganic & medicinal chemistry letters,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Design and Synthesis of 3,4-diarylpyrrole Analogues as Potent Topoisomerase Inhibitors.
January 2018, Medicinal chemistry (Shariqah (United Arab Emirates)),
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors.
January 2002, Journal of medicinal chemistry,
Masaki Ohtawa, and Shiho Arima, and Naoki Ichida, and Tomiaki Terayama, and Hironao Ohno, and Takaya Yamazaki, and Taichi Ohshiro, and Noriko Sato, and Satoshi Omura, and Hiroshi Tomoda, and Tohru Nagamitsu
Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 2.
May 2013, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!