501022-63-5Relevant academic research and scientific papers
Design and synthesis of opioidmimetics containing 2′,6′-dimethyl-l-tyrosine and a pyrazinone-ring platform
Shiotani, Kimitaka,Li, Tingyou,Miyazaki, Anna,Tsuda, Yuko,Yokoi, Toshio,Ambo, Akihiro,Sasaki, Yusuke,Bryant, Sharon D.,Lazarus, Lawrence H.,Okada, Yoshio
, p. 5768 - 5771 (2008/03/18)
Twelve 2′,6′-dimethyl-l-tyrosine (Dmt) analogues linked to a pyrazinone platform were synthesized as 3- or 6-[H-Dmt-NH(CH2)n],3- or 6-R-2(1H)-pyrazinone (n = 1-4). 3-[H-Dmt-NH-(CH2)4]-6-β-phenethyl-5-methyl-2(1H)-pyrazinone 11 bound to μ-opioid receptors with high affinity (Kiμ = 0.13 nM; Kiδ/Kiμ = 447) with μ-agonism (GPI IC50 = 15.9 nM) and weak δ-antagonism (MVD pA2 = 6.35). Key factors affecting opioid affinity and functional bioactivity are the length of the aminoalkyl chain linked to Dmt and the nature of the R residue. These data present a simplified method for the formation of pyrazinone opioidmimetics and new lead compounds.
Studies on the mechanism of 1,2-dihydropyrazin-2-one ring formation from dipeptidyl chloromethyl ketone and its chemical properties: Immediate deamination during catalytic hydrogenation
Miyazaki, Anna,Fujisawa, Yutaka,Shiotani, Kimitaka,Fujita, Yoshio,Li, Tingyou,Tsuda, Yuko,Yokoi, Toshio,Bryant, Sharon D.,Lazarus, Lawrence H.,Okada, Yoshio
, p. 1152 - 1158 (2007/10/03)
1,2-Dihydropyrazin-2-one derivatives, which have two aminoalkyl groups at the positions 3 and 6, were found to be efficient tools for the construction of potent, selective and long-acting opioid mimetics. During the course of preparation, we found that the catalytic hydrogenation of 3,6- bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove the benzyloxycarbonyl groups resulted in a side reaction. By MS and NMR studies and by preparation of additional 1,2-dihydropyrazin-2-one derivatives, the structure of the by-product was identified as 3-aminomethyl-5,6-dimethyl-1,2- dihydropyrazin-2-one. Preparation of additional compounds substituted with deuterium provided us with sufficient information to confirm the structure of the product and to support a cyclization mechanism in its formation.
Immediate deamination from the aminomethyl group attached to 1,2-dihydropyrazin-2-one derivative during catalytic hydrogenation
Okada, Yoshio,Fujisawa, Yutaka,Morishita, Akihisa,Shiotani, Kimitaka,Miyazaki, Anna,Fujita, Yoshio,Li, Tingyou,Tsuda, Yuko,Yokoi, Toshio,Bryant, Sharon D.,Lazarus, Lawrence H.
, p. 8137 - 8139 (2007/10/03)
The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove benzyloxycarbonyl (Z) groups resulted in a side reaction. Purification by reverse-phase HPLC and analysis by proton nuclear magnetic resonance
