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同二价喹唑啉亚胺作为新型纳摩尔级胆碱酯酶抑制剂，对丁酰胆碱酯酶具有可控选择性。

Homobivalent quinazolinimines as novel nanomolar inhibitors of cholinesterases with dirigible selectivity toward butyrylcholinesterase.

作者信息

Decker Michael

机构信息

Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.

出版信息

J Med Chem. 2006 Sep 7;49(18):5411-3. doi: 10.1021/jm060682m.

DOI:10.1021/jm060682m
PMID:16942014
Abstract

Homobivalent dimers of quinazolinimines, which bridge the imine nitrogen atoms via a hepta- and an octamethylene spacer, with different ring sizes of the alicycles were synthesized from the corresponding quinazolinethiones. The resulting compounds show >100-fold increase of inhibitory activities compared to related monomeric compounds yielding low-nanomolar inhibitors. For heptamethylene dimers, mixed inhibition profiles were obtained, whereas for the octamethylene compounds selectivity toward butyrylcholinesterase (>180) can be achieved with an eight-membered alicycle.

摘要

喹唑啉亚胺的同二价二聚体通过七亚甲基和八亚甲基间隔基连接亚胺氮原子，由相应的喹唑啉硫酮合成了具有不同脂环大小的化合物。与产生低纳摩尔抑制剂的相关单体化合物相比，所得化合物的抑制活性提高了100倍以上。对于七亚甲基二聚体，获得了混合抑制模式，而对于八亚甲基化合物，使用八元脂环可以实现对丁酰胆碱酯酶的选择性（>180）。

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