The role of polycyclic frameworks in modulating P2X7 receptor function

被引：8

作者：

Callis, Timothy B. ^{[1
]}

Reekie, Tristan A. ^{[1
]}

O'Brien-Brown, James ^{[1
]}

Wong, Erick C. N. ^{[2
]}

Werry, Eryn L. ^{[3
]}

Elias, Nabiha ^{[1
]}

Jorgensen, William T. ^{[1
]}

Tsanaktsidis, John ^{[4
]}

Rendina, Louis M. ^{[1
]}

Kassiou, Michael ^{[1
]}

机构：

[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[2] Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia

[3] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia

[4] CSIRO Mfg, Clayton, Vic 3169, Australia

来源：

TETRAHEDRON | 2018年 / 74卷 / 12期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

P2X(7); Polycyclic; Structure-activity relationships; Isoquinoline; Cyanoguanidine; PHARMACOLOGICAL EVALUATION; ANTAGONISTS; IL-1-BETA; MICROGLIA; RELEASE; P2X7R; MACROPHAGES; ACTIVATION; DEPRESSION; CARBORANE;

D O I：

10.1016/j.tet.2017.10.075

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Herein we describe our recent attempts to target the P2X7 receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X7 receptor. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：1207 / 1219

页数：13

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