Yao Gang, Haque Serajul, Sha Li, Kumaravel Gnanasambandam, Wang Joy, Engber Thomas M, Whalley Eric T, Conlon Patrick R, Chang Hexi, Kiesman William F, Petter Russell C
Departments of Medicinal Chemistry and Pharmacology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA.
Bioorg Med Chem Lett. 2005 Feb 1;15(3):511-5. doi: 10.1016/j.bmcl.2004.11.062.
A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure-activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A(2A) receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A(2A) receptor. Compound 12, in particular, was found to be orally active at 3mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model.
合成了一种新型的[1,2,4]三唑并[1,5 - a]吡嗪核心，并将其与末端炔烃偶联。研究了源自该新型模板的炔烃对腺苷A(2A)受体的体外和体内拮抗作用的构效关系。该系列中选定的化合物显示出对腺苷A(2A)受体具有强大的体外和体内活性。特别是化合物12，在小鼠僵住症模型和6 - 羟基多巴胺损伤大鼠模型中，以3mg/kg的剂量口服时具有活性。
