Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications.
Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications.
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DOI：
10.1021/acs.jmedchem.7b00584
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发表时间：
2017-07-27
影响因子：
7.3
通讯作者：
Kozikowski AP
中科院分区：
文献类型：
--
作者：
Zhang G;Cheng J;McCorvy JD;Lorello PJ;Caldarone BJ;Roth BL;Kozikowski AP
设计并合成了一系列n取代的2-苯基环丙基甲胺，目的是寻找优先于Gq信号传导的5- ht2c选择性激动剂。与β-阻滞蛋白募集相比，许多这些化合物表现出5-HT2C选择性，偏爱gq介导的信号传导。此外，n -甲基化合物(+)-15a在钙通量试验中显示出23 nM的EC50，而没有β-阻滞蛋白募集活性，是迄今为止报道的功能选择性最高的5-HT2C激动剂。n -苄基化合物(+)-19对5-HT2C受体的EC50为24 nM，对5-HT2B受体具有完全选择性。在安非他明诱导的多动症模型中，化合物(+)-19显示出明显的抗精神病药物样活性。这些新化合物阐明了5-HT2C受体在抗精神病活性方面的功能选择性作用。
A series of N-substituted 2-phenylcyclopropylmethylamines were designed and synthesized, with the aim of finding 5-HT2C-selective agonists with preference for Gq signaling. A number of these compounds exhibit 5-HT2C selectivity with preference for Gq-mediated signaling compared with β-arrestin recruitment. Furthermore, the N-methyl compound (+)-15a, which displayed an EC50 of 23 nM in the calcium flux assay while showing no β-arrestin recruitment activity, is the most functionally-selective 5-HT2C agonist reported to date. The N-benzyl compound (+)-19, which showed an EC50 of 24 nM at the 5-HT2C receptor, is fully selective over the 5-HT2B receptor. In an amphetamine-induced hyperactivity model, compound (+)-19 showed significant antipsychotic drug-like activity. These novel compounds shed light on the role of functional selectivity at the 5-HT2C receptor with respect to antipsychotic activity.
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影响因子：
7.6
作者：
Pogorelov, Vladimir M.;Rodriguiz, Ramona M.;Wetsel, William C.
通讯作者：
Wetsel, William C.
DOI：
10.1124/jpet.106.106989
发表时间：
2007-01-01
影响因子：
3.5
作者：
Marquis, Karen L.;Sabb, Annmarie L.;Rosenzweig-Lipson, Sharon
通讯作者：
Rosenzweig-Lipson, Sharon
2-苯基丙烷基甲胺作为选择性5-羟色胺2C受体激动剂的优化及其作为潜在抗精神病药的评估。
影响因子：
7.3
作者：
Cheng J;Giguère PM;Onajole OK;Lv W;Gaisin A;Gunosewoyo H;Schmerberg CM;Pogorelov VM;Rodriguiz RM;Vistoli G;Wetsel WC;Roth BL;Kozikowski AP
通讯作者：
Kozikowski AP
影响因子：
5
作者：
Ghose, Arup K.;Herbertz, Torsten;Hudkins, Robert L.;Dorsey, Bruce D.;Mallamo, John P.
通讯作者：
Mallamo, John P.
影响因子：
3.4
作者：
Cheng J;Kozikowski AP
通讯作者：
Kozikowski AP