Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, United States.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3715-20. doi: 10.1016/j.bmcl.2011.04.079. Epub 2011 May 1.
Herein we describe the structure-activity relationship (SAR) of amino-caprolactam analogs derived from amino-caprolactam benzene sulfonamide 1, highlighting affects on the potency of γ-secretase inhibition, selectivity for the inhibition of APP versus Notch processing by γ-secretase and selected pharmakokinetic properties. Amino-caprolactams that are efficacious in reducing the cortical Aβ(x-40) levels in FVB mice via a single 100 mpk IP dose are highlighted.
在此，我们描述了氨基己内酰胺苯磺酰胺 1 的类似物的结构-活性关系 (SAR)，重点介绍了对 γ-分泌酶抑制活性、对 γ-分泌酶抑制 APP 与 Notch 加工的选择性以及所选药代动力学性质的影响。通过单次 100mpk IP 剂量，能够有效降低 FVB 小鼠皮质 Aβ(x-40)水平的氨基己内酰胺类化合物被突出强调。
