Pinkerton Anthony B, Cube Rowena V, Hutchinson John H, James Joyce K, Gardner Michael F, Schaffhauser Hervé, Rowe Blake A, Daggett Lorrie P, Vernier Jean-Michel
Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5867-72. doi: 10.1016/j.bmcl.2004.09.028.
We have identified and synthesized a series of 4-thiopyridyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward replacement of the tetrazole in the initial lead led to the discovery of 16 (EC(50)=340 nM), which showed improved brain penetration over the initial lead.
我们已经鉴定并合成了一系列4-硫代吡啶基苯乙酮，作为代谢型谷氨酸受体2的正变构增强剂。针对最初先导化合物中四唑的取代进行的构效关系研究，导致了化合物16（EC50 = 340 nM）的发现，其在脑渗透性方面比最初的先导化合物有所改善。
