Rotella David P, McFarlane Geraldine R, Greenfield Alexander, Grosanu Cristina, Robichaud Albert J, Denny Rajiah Aldrin, Feenstra Rolf W, Núñez-García Sara, Reinders Jan-Hendrik, Neut Martina van der, McCreary Andrew, Kruse Chris G, Sullivan Kelly, Pruthi Farhana, Lai Margaret, Zhang Jean, Kowal Dianne M, Carrick Tikva, Grauer Steven M, Navarra Rachel L, Graf Radka, Brennan Julie, Marquis Karen L, Pausch Mark H
Chemical Sciences, Wyeth Research, CN 8000 Princeton, NJ 08543, United States.
Bioorg Med Chem Lett. 2009 Oct 1;19(19):5552-5. doi: 10.1016/j.bmcl.2009.08.050. Epub 2009 Aug 15.
A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.
一种5-氟-四氢咔唑血清素再摄取抑制剂（SRI）结构单元与多种连接体和多巴胺D2受体配体相结合，试图确定用于治疗精神分裂症的强效D2部分激动剂/SRI分子。与现有疗法相比，这种方法有可能治疗更广泛的症状。该系列中的选定化合物在基于细胞和体内的试验中对两个靶点均表现出高亲和力以及D2部分激动作用。
