喹啉作为极具效力和选择性的磷酸二酯酶5抑制剂，有望成为治疗勃起功能障碍的药物。
Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.
作者信息
Bi Yingzhi, Stoy Patrick, Adam Leonard, He Bin, Krupinski John, Normandin Diane, Pongrac Ron, Seliger Laurie, Watson Andrew, Macor John E
机构信息
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
出版信息
Bioorg Med Chem Lett. 2004 Mar 22;14(6):1577-80. doi: 10.1016/j.bmcl.2003.12.090.
In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC(50)'s as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity. Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure-activity relationship of this new series of potent PDE5 inhibitors are described.
为持续致力于发现新型化学类型作为治疗男性勃起功能障碍（ED）的强效且选择性的磷酸二酯酶5（PDE5）抑制剂，我们发现4-苄基氨基喹啉衍生物是非常强效且选择性的PDE5抑制剂。该系列中的一些化合物的PDE5半数抑制浓度（IC50）低至50皮摩尔。虽然喹啉C6位上的吸电子基团显著提高了PDE5活性，但C8位上的乙基不仅提高了PDE5活性，还提高了同工酶选择性。C3位上的取代基可以引入多种不同的基团。本文描述了这一系列新型强效PDE5抑制剂的合成及初步构效关系。
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