Asubio Pharma Co., Ltd, 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Asubio Pharma Co., Ltd, 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Bioorg Med Chem Lett. 2019 Jan 15;29(2):334-338. doi: 10.1016/j.bmcl.2018.11.011. Epub 2018 Nov 8.
A series of imidazolinylindole derivatives were discovered as novel kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme) inhibitors. Structure-activity relationship (SAR) studies led to the identification of potent human KLK7 inhibitors. By further modification of the benzenesulfonyl moiety to overcome species differences in inhibitory activity, potent inhibitors against both human and mouse KLK7 were identified. Furthermore, the complex structure of 25 with mouse KLK7 could explain the SAR and the cause of the species differences in inhibitory activity.
一系列咪唑啉吲哚衍生物被发现是新型激肽释放酶 7（KLK7，角质层丝氨酸蛋白酶）抑制剂。构效关系（SAR）研究导致了有效的人类 KLK7 抑制剂的鉴定。通过进一步修饰苯磺酰基部分以克服抑制活性的种属差异，鉴定出对人和鼠 KLK7 均具有抑制活性的有效抑制剂。此外，与鼠 KLK7 的 25 的复合物结构可以解释 SAR 和抑制活性的种属差异的原因。
