Gong Paul K, Blough Bruce E, Brieaddy Lawrence E, Huang Xiaodong, Kuhar Michael J, Navarro Hernán A, Carroll F Ivy
Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA.
J Med Chem. 2007 Jul 26;50(15):3686-95. doi: 10.1021/jm0703035. Epub 2007 Jun 30.
Synthetic methods were developed for the synthesis of the 3beta-(4-substituted phenyl)-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3beta-(4-methylphenyl-2 beta-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).
已开发出合成3β-(4-取代苯基)-2β-[5-(取代苯基)噻唑-2-基]托烷(4a - s)的合成方法。使用大鼠脑组织和克隆转运体测定法评估了这些化合物的单胺转运体结合和单胺摄取抑制特性。一般来说，相对于血清素和去甲肾上腺素转运体（分别为SERT和NET），这些化合物显示出更高的多巴胺转运体（DAT）亲和力，并且相对于[3H]血清素和[3H]去甲肾上腺素摄取抑制，具有更强的[3H]多巴胺摄取抑制效力。在单胺转运体结合测定中，相对于SERT和NET，几种化合物对DAT具有选择性。在功能性单胺摄取抑制试验中，最有效和选择性最强的类似物是3β-(4-甲基苯基)-2β-[5-(3-硝基苯基)噻唑-2-基]托烷(4p)。
