477533-91-8Relevant academic research and scientific papers
A novel series of (S)-2,7-substituted-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acids: Peroxisome proliferator-activated receptor α/γ dual agonists with protein-tyrosine phosphatase 1B inhibitory activity
Otake, Kazuya,Azukizawa, Satoru,Fukui, Masaki,Shibabayashi, Michiko,Kamemoto, Hikaru,Miike, Tomohiro,Kunishiro, Kazuyoshi,Kasai, Masayasu,Shirahase, Hiroaki
, p. 1233 - 1242 (2011/11/06)
Novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-7-(2-{2-[(E)-2-cyclopentylvinyl]-5-methyloxazol-4-yl}ethoxy) -2-[(2E,4E)-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14c) was identified as a peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist. The transactivation activity of 14c was comparable to that of rosiglitazone in human PPARg (EC50=0.14μM) and was much higher than in human PPARα (EC50=0.20μM). In addition, 14c, but not rosiglitazone, showed human protein-tyrosine phosphatase 1B (PTP-1B) inhibitory activity (IC50=1.85μM). 14c showed about 10-fold stronger hypoglycemic and hypotriglyceridemic effects than rosiglitazone by repeated application for 14 d in male KK-Aymice. Furthermore, 14c, but not rosiglitazone, increased hepatic peroxisome acyl CoA oxidase activity at 30 mg/kg/d for 7 d in male Syrian hamsters, probably due to its PPARα agonist activity. 14c did not affect plasma volume at 100 mg/kg/d for 14 d in male ICR mice, while rosiglitazone significantly increased it. In conclusion, 14c is a promising candidate for an efficacious and safe anti-diabetic drug with triple actions as a PPARα/γ dual agonist with PTP-1B inhibitory activity.
NOVEL HETEROCYCLIC COMPOUND AND MEDICINAL USE THEREOF
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Page 53, (2008/06/13)
The novel heterocyclic compound of the present invention is a novel heterocyclic compound having the formula (I)R15―C(R14)=N-O― wherein R1 is H or C1-6 alkyl, R2 is H, -CO-C(R4)=C(R4)-R5 wherein R4 is H or C1-4 alkyl, and R5 is C4-8 alkyl, C2-8 alkenyl and the like, and the like, Y is the following group wherein X is O or S, R7 is the same as R4, R8 is R10-C(R9)=C(R9)- wherein R9 is the same as R4, R10 is C3-6 alkyl and the like, and the like, R14 is the same as R4, and R15 is aryl and the like, Y-(CH2)n-O- is bonded to the 6- or 7-position of the tetrahydroisoquinoline skeleton, and n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof. The compound (I) of the present invention is useful as a hypoglycemic agent, a hypolipidemic agent, an insulin resistance improver, a therapeutic agent of diabetes, a therapeutic agent of diabetic complications, a glucose tolerance improver, an anti-arteriosclerosis agent, an anti-obesity agent, an antiinflammatory agent, an agent for the prophylaxis or treatment of PPAR-mediated diseases or an agent for the prophylaxis or treatment of syndrome X.
