Diphenyl purine derivatives as peripherally selective cannabinoid receptor 1 antagonists.
Diphenyl purine derivatives as peripherally selective cannabinoid receptor 1 antagonists.
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DOI：
10.1021/jm301181r
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发表时间：
2012-11-26
影响因子：
7.3
通讯作者：
Maitra, Rangan
中科院分区：
文献类型：
--
作者：
Pulp, Alan;Bortoff, Katherine;Zhang, Yanan;Seltzman, Herbert;Mathews, James;Snyder, Rodney;Fennell, Tim;Maitra, Rangan
大麻素受体1 （CB1）拮抗剂可用于治疗多种疾病。然而，由于中枢神经系统（CNS）相关的副作用，包括一些使用者的抑郁和自杀意念，几种CB1拮抗剂的临床开发被停止。最近，研究表明，选择性调节外周CB1受体是治疗几种重要疾病的可行策略。过去开发CB1的外周选择性拮抗剂的努力主要针对利莫那班，一种CB1的逆激动剂。本文报道了我们开发基于奥特纳班支架的外周选择性CB1拮抗剂的努力。尽管奥特纳班特能穿透中枢神经系统，但它在经过临床测试的CB1拮抗剂中是独一无二的，因为它具有通常与外周选择性化合物相关的特性。我们的努力已经产生了一种口服吸收的化合物，它是一种有效的选择性CB1拮抗剂，对中枢神经系统的渗透有限。
Cannabinoid receptor 1 (CB1) antagonists are potentially useful for the treatment of several diseases. However, clinical development of several CB1 antagonists was halted due to central nervous system (CNS)-related side effects including depression and suicidal ideation in some users. Recently, studies have indicated that selective regulation of CB1 receptors in the periphery is a viable strategy for treating several important disorders. Past efforts to develop peripherally selective antagonists of CB1 have largely targeted rimonabant, an inverse agonist of CB1. Reported here are our efforts toward developing a peripherally selective CB1 antagonist based on the otenabant scaffold. Even though otenabant penetrates the CNS, it is unique among CB1 antagonists that have been clinically tested because it has properties that are normally associated with peripherally selective compounds. Our efforts have resulted in an orally absorbed compound that is a potent and selective CB1 antagonist with limited penetration into the CNS.
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影响因子：
3.9
作者：
Doran, A;Obach, RS;Zhang, CH
通讯作者：
Zhang, CH
影响因子：
2.7
作者：
LoVerme J;Duranti A;Tontini A;Spadoni G;Mor M;Rivara S;Stella N;Xu C;Tarzia G;Piomelli D
通讯作者：
Piomelli D
影响因子：
7.3
作者：
Griffith, David A.;Hadcock, John R.;Scott, Dennis O.
通讯作者：
Scott, Dennis O.
DOI：
10.1016/j.bbrc.2010.03.015
发表时间：
2010-04-02
影响因子：
3.1
作者：
Hadcock, John R.;Griffith, David A.;Scott, Dennis O.
通讯作者：
Scott, Dennis O.
影响因子：
2.7
作者：
Receveur, Jean-Marie;Murray, Anthony;Hogberg, Thomas
通讯作者：
Hogberg, Thomas