1-(p-methoxybenzylmercapto)-2-bromoethane | 188727-96-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(p-methoxybenzylmercapto)-2-bromoethane
• 英文别名: 2-(4-methoxybenzylthio)ethyl bromide；2-(p-methoxybenzylthio)ethyl bromide；1-{[(2-Bromoethyl)sulfanyl]methyl}-4-methoxybenzene；1-(2-bromoethylsulfanylmethyl)-4-methoxybenzene
• CAS: 188727-96-0
• 化学式: C₁₀H₁₃BrOS
• 分子量: 261.183
• InChiKey: QJNZYRNMEHMURS-UHFFFAOYSA-N

物化性质

• 沸点：
  323.4±27.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(p-methoxybenzylmercapto)-2-bromoethane 在 盐酸 、 草酰氯 、 sodium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 109.0h， 生成 N-[2'-(p-methoxybenzylmercapto)ethyl]-3β-(p-chlorophenyl)nortropane-2β-[N'-2'-(p-methoxybenzylmercapto)ethyl]carboxamide
  参考文献：
  名称：

  Technetium-99m labelled integrated tropane–BAT as a potential dopamine transporter tracer

  摘要：

  To reduce the molecular weight of Tc-99m-labelled tropanes with the aim to enhance the passage over the blood-brain barrier, a so-called integrated tropane-BAT construct was developed. For this purpose a mercaptoethyl substituent was attached to the amine nitrogen atom of a nortropane precursor and the methyl carboxylate in 2beta-position was converted to a 2-mercaptoethylaminomethylene substituent. This integrated tropane-BAT construct could be labelled efficiently (85-90%) with technetium-99m. Results of LC-MS analysis of the tracer agent support the assumed structure. Biodistribution studies in normal rats (n = 3) showed a slightly higher brain uptake for the new tracer agents as compared to Tc-99m-TRODAT-1. These results indicate that further biological evaluation of the integrated Tc-99m-tropane-BAT is warranted. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.036
• 作为产物：
  描述：

  2-<<(4-methoxyphenyl)methyl>thio>ethanol 、 三溴化磷 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 1-(p-methoxybenzylmercapto)-2-bromoethane
  参考文献：
  名称：

  Thiol ligands and complexes for X-ray imaging

  摘要：

  本发明提供了新的结构多样的组合物，包括符合以下一般式的化合物：##STR1## 其中R.sup.1、R.sup.2、R.sup.3、R.sup.4和R.sup.5相同或不同，分别为--CO--(CH.sub.2).sub.y --SH、--(CH.sub.2).sub.2 --SH、--SO.sub.2 --(SH.sub.2).sub.t --SH、--SH、--(CH.sub.2).sub.q --COOH和--(CH.sub.2).sub.v --CONR.sup.6 R.sup.7，至少其中之一为含硫基团；n为0至约10；i为2至约5；j为2至约5；y为1至约5；z为1至约6；t为1至约5；q为1至约5；v为1至约5；R.sup.6为H、烷基、羟基烷基、多羟基烷基、芳基烷基或烷氧基烷基；R.sup.7为H、烷基、羟基烷基、多羟基烷基、芳基烷基或烷氧基烷基；当R.sup.6为H时，R.sup.7可以是多胺。本发明还提供了使用该组合物进行成像的方法。

  公开号：

  US05616312A1

文献信息

• Design, synthesis and structure–activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents
  作者：Jinhe Pan、Neale S. Mason、Manik L. Debnath、Chester A. Mathis、William E. Klunk、Kuo-Shyan Lin

  DOI：10.1016/j.bmcl.2013.01.068

  日期：2013.3

  To continue our efforts toward the development of Tc-99m PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of Tc-99m) 2-arylbenzothiazoles, and explored their structure-activity relationship for binding to A beta(1-40) fibrils. These Re complexes were designed and synthesized via the integrated approach, so their 99mTc analogs would have a greater chance of crossing the blood-brain barrier. While the lipophilicities (logP(C18) = 1.59-3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (K-i = 30-617 nM) to A beta(1-40) fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Ab PET tracers to their Tc-99m analogs for more widespread application via the use of SPECT scanners. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and β-amyloid binding properties of rhenium 2-phenylbenzothiazoles
  作者：Kuo-Shyan Lin、Manik L. Debnath、Chester A. Mathis、William E. Klunk

  DOI：10.1016/j.bmcl.2009.02.096

  日期：2009.4

  As a first step toward the development of (99m)Tc PiB analogs, we have synthesized six neutral Re 2-phenylbenzothiazoles via pendant or integrated approach. These Re compounds bind to A beta(1-40) fibrils with fairly good affinities (K(i) = 10.0-88.6 nM) and have moderate lipophilicities (logP(C18) = 1.21-3.26). The Re compounds prepared via the integrated approach are smaller in size, and therefore their corresponding 99mTc analogs would have a greater chance of crossing the blood-brain barrier well. For potential clinical applications, further optimization on the structure-activity relationship to obtain Re 2-phenylbenzothiazoles with higher binding affinities (< 10 nM) might be needed. The integrated approach reported here to obtain neutral, compact and lipophilic Re 2-phenylbenzothiazoles could to be applied to other high affinity pharmacophores as well as to generate (99m)Tc analogs that could hold promise for extending the use of Ab imaging in living human brain to many more clinical settings because they could be used with SPECT. (c) 2009 Elsevier Ltd. All rights reserved.
• US5616312A
  申请人：——

  公开号：US5616312A

  公开（公告）日：1997-04-01
• Technetium-99m labelled integrated tropane–BAT as a potential dopamine transporter tracer
  作者：Bernard J. Cleynhens、Tjibbe J. de Groot、Hubert P. Vanbilloen、Davy Kieffer、Luc Mortelmans、Guy M. Bormans、Alfons M. Verbruggen

  DOI：10.1016/j.bmc.2004.11.036

  日期：2005.2

  To reduce the molecular weight of Tc-99m-labelled tropanes with the aim to enhance the passage over the blood-brain barrier, a so-called integrated tropane-BAT construct was developed. For this purpose a mercaptoethyl substituent was attached to the amine nitrogen atom of a nortropane precursor and the methyl carboxylate in 2beta-position was converted to a 2-mercaptoethylaminomethylene substituent. This integrated tropane-BAT construct could be labelled efficiently (85-90%) with technetium-99m. Results of LC-MS analysis of the tracer agent support the assumed structure. Biodistribution studies in normal rats (n = 3) showed a slightly higher brain uptake for the new tracer agents as compared to Tc-99m-TRODAT-1. These results indicate that further biological evaluation of the integrated Tc-99m-tropane-BAT is warranted. (C) 2004 Elsevier Ltd. All rights reserved.
• Thiol ligands and complexes for X-ray imaging
  申请人：Mallinckrodt Medical, Inc.

  公开号：US05616312A1

  公开（公告）日：1997-04-01

  The present invention provides new and structurally diverse compositions comprising compounds of the general formula: ##STR1## Wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are the same or different and are --CO--(CH.sub.2).sub.y --SH, --(CH.sub.2).sub.2 --SH, --SO.sub.2 --(SH.sub.2).sub.t --SH,--SH,--(CH.sub.2).sub.q --COOH, and --(CH.sub.2).sub.v --CONR.sup.6 R.sup.7, provided at least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 is a sulfur containing moiety; n is 0 to about 10; i is 2 to about 5; j is 2 to about 5; y is 1 to about 5; z is 1 to about 6; t is 1 to about 5; q is 1 to about 5; v is 1 to about 5; R.sup.6 is H, alkyl, hydroxyalkyl, polyhydroxyalkyl, arylalkyl or alkoxyalkyl; R.sup.7 is H, alkyl, hydroxyalkyl, polyhydroxyalkyl, arylalkyl or alkoxyalkyl; and R.sup.7 can be polyamine when R.sup.6 is H. Methods for imaging using compositions of the invention are also provided.

  本发明提供了新的结构多样的组合物，包括符合以下一般式的化合物：##STR1## 其中R.sup.1、R.sup.2、R.sup.3、R.sup.4和R.sup.5相同或不同，分别为--CO--(CH.sub.2).sub.y --SH、--(CH.sub.2).sub.2 --SH、--SO.sub.2 --(SH.sub.2).sub.t --SH、--SH、--(CH.sub.2).sub.q --COOH和--(CH.sub.2).sub.v --CONR.sup.6 R.sup.7，至少其中之一为含硫基团；n为0至约10；i为2至约5；j为2至约5；y为1至约5；z为1至约6；t为1至约5；q为1至约5；v为1至约5；R.sup.6为H、烷基、羟基烷基、多羟基烷基、芳基烷基或烷氧基烷基；R.sup.7为H、烷基、羟基烷基、多羟基烷基、芳基烷基或烷氧基烷基；当R.sup.6为H时，R.sup.7可以是多胺。本发明还提供了使用该组合物进行成像的方法。