Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 Labeled 2-Carbomethoxy-3![]()
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- 作者：Jeffrey S. Stehouwer ; Nachwa Jarkas ; Fanxing Zeng ; Ronald J. Voll ; Larry Williams ; Michael J. Owens ; John R. Votaw ; Mark M. Goodman
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：November 16, 2006
- 年：2006
- 卷：49
- 期：23
- 页码：6760 - 6767
- 全文大小：203K
- 年卷期：v.49,no.23(November 16, 2006)
- ISSN：1520-4804
文摘
2![]()
RC="/images/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-Carbomethoxy-3
rs/beta2.gif" BORDER=0 ALIGN="middle">-(3'-((Z)-2-iodoethenyl)phenyl)nortropane (mZIENT, 1) and 2rs/beta2.gif" BORDER=0 ALIGN="middle">-carbomethoxy-3rs/beta2.gif" BORDER=0 ALIGN="middle">-(3'-((Z)-2-bromoethenyl)phenyl)nortropane (mZBrENT, 2) were synthesized and evaluated for binding to thehuman serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively) usingtransfected cells. Both 1 and 2 have a high affinity for the SERT (Ki = 0.2 nM) and are ~160 times moreselective for the SERT than the DAT. Compound 2 has a significantly higher affinity for the NET than 1,and this may be a result of the different size and electronegativity of the halogen atoms. MicroPET imagingin nonhuman primates with [11C]1 and [11C]2 demonstrated that both tracers behave similarly in vivo withhigh uptake being observed in the SERT-rich brain regions and peak uptake being achieved in about 55 minpostinjection. Chase studies with citalopram and methylphenidate demonstrated that this uptake is the resultof preferential binding to the SERT.
rs/beta2.gif" BORDER=0 ALIGN="middle">-(3'-((Z)-2-iodoethenyl)phenyl)nortropane (mZIENT, 1) and 2rs/beta2.gif" BORDER=0 ALIGN="middle">-carbomethoxy-3rs/beta2.gif" BORDER=0 ALIGN="middle">-(3'-((Z)-2-bromoethenyl)phenyl)nortropane (mZBrENT, 2) were synthesized and evaluated for binding to thehuman serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively) usingtransfected cells. Both 1 and 2 have a high affinity for the SERT (Ki = 0.2 nM) and are ~160 times moreselective for the SERT than the DAT. Compound 2 has a significantly higher affinity for the NET than 1,and this may be a result of the different size and electronegativity of the halogen atoms. MicroPET imagingin nonhuman primates with [11C]1 and [11C]2 demonstrated that both tracers behave similarly in vivo withhigh uptake being observed in the SERT-rich brain regions and peak uptake being achieved in about 55 minpostinjection. Chase studies with citalopram and methylphenidate demonstrated that this uptake is the resultof preferential binding to the SERT.