琥珀酸酰胺作为白细胞介素-1β转化酶（ICE 或半胱天冬酶 1）抑制剂的 P2-P3 替代品。
Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1).
机构信息
Pfizer Global R&D, Ann Arbor, MI 48105, USA.
出版信息
Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90. doi: 10.1016/j.bmcl.2010.07.004. Epub 2010 Jul 8.
PMID:20656488
Abstract
Succinic acid amides have been found to be effective P2-P3 scaffold replacements for peptidic ICE inhibitors. Heteroarylalkyl fragments occupying the P4 position provided access to compounds with nM affinities. Utilization of an acylal prodrug moiety was required to overcome biopharmaceutical issues which led to the identification of 17f, a potential clinical candidate.
摘要
琥珀酸酰胺已被发现是有效的 P2-P3 支架肽 ICE 抑制剂替代物。占据 P4 位置的杂芳基烷基片段提供了具有纳摩尔亲和力的化合物。需要利用酰基前药部分来克服生物制药问题，这导致了 17f 的鉴定，它是一种有潜力的临床候选药物。
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