H. Lundbeck A/S, Department of Discovery Chemistry & DMPK, Valby, Denmark.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3738-42. doi: 10.1016/j.bmcl.2011.04.067. Epub 2011 Apr 30.
Novel triazoloquinazolines have been found as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity studies improved the initial micromolar potency which was found in the lead compound by a 100-fold identifying 5-(1H-benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5-c]quinazoline, 42 (PDE10A IC(50)=12 nM) as the most potent compound from the series. Two X-ray structures revealed novel binding modes to the catalytic site of the PDE10A enzyme.
新型三唑并喹唑啉已被发现为磷酸二酯酶 10A（PDE10A）抑制剂。构效关系研究提高了先导化合物的初始微摩尔效力，通过 100 倍的筛选，确定 5-(1H-苯并咪唑-2-基甲基硫基)-2-甲基-[1,2,4]三唑并[1,5-c]喹唑啉，42（PDE10A IC（50）=12 nM）为该系列中最有效的化合物。两个 X 射线结构揭示了与 PDE10A 酶催化位点的新型结合模式。
