Synthesis, Monoamine Transporter Binding, Properties, and Functional Monoamine Uptake Activity of 3-[4-Methylphenyl a
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- 作者：Paul K. Gong ; Bruce E. Blough ; Lawrence E. Brieaddy ; Xiaodong Huang ; Michael J. Kuhar ; Herná ; n A. Navarro ; F. Ivy Carroll
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：July 26, 2007
- 年：2007
- 卷：50
- 期：15
- 页码：3686 - 3695
- 全文大小：132K
- 年卷期：v.50,no.15(July 26, 2007)
- ISSN：1520-4804
文摘
Synthetic methods were developed for the synthesis of the 3
-(4-substituted phenyl)-2-[5-(substitutedphenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter bindingand monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. Ingeneral, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin andnorepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potencyrelative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selectiverelative to the SERT and NET in the monoamine transporter binding assays. The most potent and selectiveanalog in the functional monoamine uptake inhibition test was 3-(4-methylphenyl-2-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).
-(4-substituted phenyl)-2-[5-(substitutedphenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter bindingand monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. Ingeneral, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin andnorepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potencyrelative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selectiverelative to the SERT and NET in the monoamine transporter binding assays. The most potent and selectiveanalog in the functional monoamine uptake inhibition test was 3-(4-methylphenyl-2-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).