We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor (S)-3 readily attains free plasma concentrations above PDE1 IC₅₀ values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue. These compounds represent promising new tools to probe the value of PDE1 inhibition in the treatment of cardiovascular disease.

中文翻译：

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环状核苷酸磷酸二酯酶PDE1的有效和选择性外围限制喹唑啉抑制剂的发现。

我们公开了有效的，选择性的PDE1喹唑啉抑制剂的发现和X射线共晶数据。抑制剂（S）-3的游离血浆浓度容易达到PDE1 IC ₅₀值以上，并且大脑进入受限。外消旋化合物3在人心肌的可溶性样品中抑制> 75％的PDE水解活性，这与该组织中PDE1活性的提高一致。这些化合物代表了有前途的新工具，可探讨PDE1抑制作用在心血管疾病治疗中的价值。