新型吡唑基硫醚类组织蛋白酶 S 抑制剂的发现和 SAR 研究。第 2 部分：P3、P4 和 P5 区域的修饰。
Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: Modification of P3, P4, and P5 regions.
机构信息
Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
出版信息
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2375-8. doi: 10.1016/j.bmcl.2010.01.104. Epub 2010 Feb 1.
A novel class of tetrahydropyrido-pyrazole thioether amines that display potency against human Cathepsin S have been previously reported. Here, further SAR investigations of the P3, P4, and P5 regions are described. In particular, 4-fluoropiperidine is identified as a competent P3 binding element when utilized in conjunction with a (S)-2-hydroxypropyl linker-containing P5 moiety and oxamide or sulfonamide P4 substitution.
先前曾有报道称，一类新型的四氢吡啶-吡唑硫醚胺类化合物对人组织蛋白酶 S 具有很强的抑制作用。在此，进一步描述了 P3、P4 和 P5 区域的 SAR 研究。特别地，当与含有 (S)-2-羟丙基连接子的 P5 部分以及噁酰胺或磺酰胺 P4 取代基一起使用时，4-氟哌啶被确定为有效的 P3 结合元件。
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