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设计、合成及氮杂双环[2.2.2]辛烷和吡咯烷衍生物作为双重去甲肾上腺素再摄取抑制剂和 5-HT(1A)部分激动剂的药理学评价。

Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine derivatives as dual norepinephrine reuptake inhibitors and 5-HT(1A) partial agonists.

机构信息

Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, United States.

出版信息

Bioorg Med Chem Lett. 2011 Jan 15;21(2):865-8. doi: 10.1016/j.bmcl.2010.11.066. Epub 2010 Nov 21.

DOI:10.1016/j.bmcl.2010.11.066
PMID:21185183
Abstract

Compounds with combined norepinephrine reuptake inhibitor (NRI) and serotonin 1A (5-HT(1A)) partial agonist pharmacology may offer a new therapeutic approach for treating symptoms of neuropsychiatric disorders including ADHD, depression, and anxiety. Herein we describe the design and optimization of novel chemical matter that exhibits favorable dual NRI and 5-HT(1A) partial agonist activity. Lead compounds in this series were found to be devoid of activity at the dopamine transporter and were shown to be brain penetrant with high receptor occupancy.

摘要

具有去甲肾上腺素再摄取抑制剂（NRI）和 5-羟色胺 1A（5-HT1A）部分激动剂药理学双重作用的化合物可能为治疗包括 ADHD、抑郁和焦虑在内的神经精神疾病的症状提供一种新的治疗方法。在此，我们描述了具有有利的双重 NRI 和 5-HT1A 部分激动剂活性的新型化学物质的设计和优化。该系列的先导化合物被发现对多巴胺转运体没有活性，并表现出脑穿透性和高受体占有率。

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