We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.

中文翻译：

---

3- [4-（2-羟乙基）哌嗪-1-基] -7-（6-甲氧基吡啶-3-基）-1-（2-丙氧基乙基）吡啶[3,4-]的设计，合成及生物学评价b ] pyrazin-2（1 H）-one，一种有效的，口服活性的磷酸二酯酶5（PDE5）的脑渗透抑制剂。

我们最近描述了一系列新颖的氨基吡啶并吡嗪酮类化合物作为PDE5抑制剂。优化该系列的努力最终确定了3- [4-（2-羟乙基）哌嗪-1-基] -7-（6-甲氧基吡啶-3-基）-1-（2-丙氧基乙基）吡啶基[3]。 ，4 - b ]吡嗪-2（1 H）-一，具有出色的效能和选择性，并在自发性高血压大鼠（SHR）模型中显示出强大的体内降压作用。此外，该化合物是脑渗透剂，并且将是用于评估中枢抑制PDE5的治疗潜力的有用试剂。该化合物最近已进入临床试验。