68276-37-9Relevant academic research and scientific papers
Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition
Otake, Kazuya,Azukizawa, Satoru,Fukui, Masaki,Kunishiro, Kazuyoshi,Kamemoto, Hikaru,Kanda, Mamoru,Miike, Tomohiro,Kasai, Masayasu,Shirahase, Hiroaki
, p. 1060 - 1075 (2012)
A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)-hexadienoyl]-7-(2-{5-methyl-2- [(1E)-5-methylhexen-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor γ (PPARγ) selective agonist (EC 50 = 0.03 μM) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC50 = 1.18 μM). Cmax after oral administration of 14i at 10 mg/kg was 2.2 μg/ml (4.5 μM) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED50 = 4.3 and 23 mg/kg/day, respectively, in male KK-Ay mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPARγ and PTP-1B.
Solid phase synthesis of alkenes using the Horner-Wadsworth-Emmons reaction and monitoring by gel phase 31P NMR
Johnson,Zhang
, p. 9253 - 9256 (2007/10/02)
Phosphonoacetamide esters bound to solid supported peptides or peptide synthesis supports are active as Horner-Wadsworth-Emmons (HWE) reagents with a variety of aldehydes. HWE reagents can be attached to the solid support via the amide or phosphono ester. Mild basic conditions, triethylamine and Li salts, with excess aldehyde give high conversions to alkenes.
