title: 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.
abstract: 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-A(y) mice. In conclusion, 14 would be an excellent lead compound for a new type of anti-diabetic drug with triple actions.
authors: Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Nakagyo-ku, Kyoto, Japan.
authors: Kazuya
authors: K
authors: Otake
authors: Satoru
authors: S
authors: Azukizawa
authors: Kenji
authors: K
authors: Takahashi
authors: Masaki
authors: M
authors: Fukui
authors: Michiko
authors: M
authors: Shibabayashi
authors: Hikaru
authors: H
authors: Kamemoto
authors: Masayasu
authors: M
authors: Kasai
authors: Hiroaki
authors: H
authors: Shirahase
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C561811:(S)-2-(2,4-hexadienoyl)-7-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D044005:Tetrahydroisoquinolines; C078986:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1