2-Acyl-tetrahydroisoquinoline-3-carboxylic Acids: Lead Compounds with Triple Actions, Peroxisome Proliferator-Activated Receptor α/γ Agonist and Protein-Tyrosine Phosphatase 1B Inhibitory Activities
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概要
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2-Acyl-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-(2,4-Hexadienoyl)-7-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14) showed peroxisome proliferator-activated receptor γ (PPARγ) and PPARα agonist activities and protein-tyrosine phosphatase 1B (PTP-1B) inhibitory activities. PPARγ agonist activity of 14 was comparable to that of rosiglitazone, and PTP-1B inhibitory activity was about 10-fold weaker than that of ertiprotafib, a PTP-1B inhibitor. Compound 14 showed high oral absorption in rats and potent hypoglycemic effects in KK-Ay mice. In conclusion, 14 would be an excellent lead compound for a new type of anti-diabetic drug with triple actions.
著者
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Takahashi K
Faculty Of Pharmaceutical Sciences Hoshi University
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Takahashi K
School Of Pharmaceutical Sciences Kitasato University
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Takahashi Kenji
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Kasai Masayasu
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Shirahase Hiroaki
Research Laboratories Kyoto Pharmaceutical Company Ltd.
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AZUKIZAWA Satoru
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Otake Kazuya
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Fukui Masaki
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Shibabayashi Michiko
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Kamemoto Hikaru
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.
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Takahashi Kenji
Research And Development Group Japan Energy Corporation
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Kasai Masayasu
Research Laboratories, Kyoto Pharmaceutical Industries
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