3-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)propyl benzoate | 1350296-22-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)propyl benzoate
• 英文别名: 3-(2-oxo-3H-1,3-benzothiazol-6-yl)propyl benzoate
• CAS: 1350296-22-8
• 化学式: C₁₇H₁₅NO₃S
• 分子量: 313.377
• InChiKey: KEHSVOQENQBINA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)propyl benzoate 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-(2-(azepan-1-yl)ethyl)-6-(3-hydroxypropyl)benzo[d]-thiazol-2(3H)-one hydrochloride
  参考文献：
  名称：

  New Positron Emission Tomography (PET) Radioligand for Imaging σ-1 Receptors in Living Subjects

  摘要：

  sigma-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([F-18]FTC-146, [F-18]13). [F-18]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 +/- 1.2 Ci/mu mol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [F-18]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [F-18]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [F-18]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [F-18]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

  DOI：

  10.1021/jm300371c
• 作为产物：
  描述：

  6-(3-chloropropyl)benzo[d]thiazol-2(3H)-one 以62的产率得到3-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)propyl benzoate
  参考文献：
  名称：

  J. Med. Chem. 2012, 55, 8272-8282

  摘要：

  DOI：

文献信息

• HIGHLY SELECTIVE SIGMA RECEPTOR RADIOLIGANDS
  申请人：McCurdy Christopher R.

  公开号：US20110280804A1

  公开（公告）日：2011-11-17

  Compounds having the general formula III′, or IV′ wherein R 1 can be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: R 2,4,5,6 can each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y is S; Z can be either H, O, S, S—R or NR where R groups can be either H, aryls, alkyls, or cycloalkyls; “n” can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging R 1 and N can be a substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C 3 -C 5 cycloalkyl group, aromatic, and heterocyclic group; and wherein X is C 1 -C 4 radiohaloalkyl.

  具有通式III'或IV'的化合物，其中R1可以是一个可选取代的C-4到C-7含氮杂环的基团，或者是一个可选取代的环状或非环状三级胺或异吲哚啉-1,3-二酮的基团；R2、4、5、6可以各自独立地是以下任何一种或组合：氰基、硝基、酰基、烷基、酰胺基、偶氮基、异硫氰酸酯基、异氰酸酯基、可选取代的苯胺基、卤素、醚、磺酰胺基、硫代酰基、芳香族、杂环、烯烃、乙炔、氘或氚；Y是S；Z可以是H、O、S、S-R或NR，其中R基团可以是H、芳基、烷基或环烷基；“n”可以是1到5个碳原子，包括立体异构体、功能类似物和药物可接受的盐；其中桥接R1和N的基团可以是取代的烷基、可选取代的烯基或可选取代的炔基，其中烷基可以包括插入的C3-C5环烷基、芳香族和杂环基团；X为C1-C4放射性卤代烷基。
• HIGHLY SELECTIVE SIGMA RECEPTOR LIGANDS AND RADIOLIGANDS AS PROBES IN NOCICEPTIVE PROCESSING AND THE PATHPHYSIOLOGICAL STUDY OF MEMORY DEFICITS AND COGNITIVE DISORDERS
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20140328755A1

  公开（公告）日：2014-11-06

  A method for localizing and quantifying S1R role in nociceptive processing; for providing a guide to providing an analgesic therapy; of using an S1R selective ligand as a biomarker for pathphysiological study of memory deficits and cognitive disorders; or of detecting increased S1R density at the site of nerve injury arising from neuropathic pain comprising using as a probe at least one SR1 selective compound or radioligand of the general formula III′, or IV′:

  一种定位和量化S1R在伤害处理中的作用的方法；为提供镇痛疗法提供指导；使用S1R选择性配体作为记忆缺陷和认知障碍的病理生理研究的生物标志物；或者使用至少一种SR1选择性化合物或放射性配体作为探针，检测神经病理性疼痛引起的神经损伤部位的S1R密度增加，其化学结构为通式III'或IV'。
• Improved protocol for the radiosynthesis of [ ¹⁸ F]FTC‐146: A potent and selective sigma‐1 receptor radioligand
  作者：Masoud Sadeghzadeh、Barbara Wenzel、Julia Nikodemus、Alexandru Florea、Fabian Hertel、Klaus Kopka、Andreas T. J. Vogg、Fabian Kiessling、Felix M. Mottaghy

  DOI：10.1002/jlcr.4018

  日期：2023.3

  [18F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4–7% was not satisfactory to us, and efforts were made to improve it. Herein, we describe an improved approach for the radiosynthesis of [18F]FTC-146 resulting in a RCY, which is sevenfold higher than that previously reported. A tosylate precursor was synthesized and radio-fluorination experiments were performed via aliphatic nucleophilic substitution reactions using either K[18F]F-Kryptofix®222 (K2.2.2)-carbonate system or tetra-n-butylammonium [18F]fluoride ([18F]TBAF). Several parameters affecting the radiolabeling reaction such as solvent, 18F-fluorination agent with the corresponding amount of base, labeling time, and temperature were investigated. Best labeling reaction conditions were found to be [18F]TBAF and acetonitrile as solvent at 100°C. The new protocol was then translated to an automated procedure using a FX2 N synthesis module. Finally, the radiotracer reproducibly obtained with RCYs of 41.7 ± 4.4% in high radiochemical purity (>98%) and molar activities up to 171 GBq/μmol.

  [18F]FTC-146是一种非常有效且具有选择性的sigma-1受体放射性配体，它作为正电子发射断层扫描神经病理性疼痛成像剂的应用前景广阔。为了配合一个有关动物福利的多实验室项目，我们选择了这种放射性配体来研究它在检测肿瘤动物的神经病理性疼痛和组织损伤方面的潜力。然而，4-7%左右的放射化学收率（RCY）并不能令我们满意，因此我们一直在努力改进。在此，我们介绍了一种改进的[18F]FTC-146 辐射合成方法，其 RCY 比以前报道的方法高出七倍。我们合成了一种对甲苯磺酸盐前体，并使用 K[18F]F-Kryptofix®222 (K2.2.2)-carbonate 体系或[18F]氟化四正丁基铵（[18F]TBAF）通过脂肪族亲核取代反应进行了放射性氟化实验。研究了影响放射性标记反应的几个参数，如溶剂、18F-氟化剂与相应量的碱基、标记时间和温度。结果发现，[18F]TBAF 和乙腈作为溶剂，温度为 100°C，是最佳的标记反应条件。然后，使用 FX2 N 合成模块将新方案转化为自动程序。最后，放射性示踪剂以高放射化学纯度（>98%）和最高 171 GBq/μmol 的摩尔活度重复获得，RCYs 为 41.7 ± 4.4%。
• HIGHLY SELECTIVE SIGMA RECEPTOR LIGANDS AND RADIOLIGANDS AS PROBES IN NOCICEPTIVE PROCESSING AND THE PATHPHYSIOLOGICAL STUDY OF MEMORY DEFICITS AND CONITIVE DISORDERS
  申请人：The University Of Mississippi

  公开号：EP3102204A2

  公开（公告）日：2016-12-14
• HIGHLY SELECTIVE SIGMA 1 RECEPTOR LIGANDS AND RADIOLIGANDS AS PROBES IN NOCICEPTIVE PROCESSING AND THE PATHOPHYSIOLOGICAL STUDY OF MEMORY DEFICITS AND COGNITIVE DISORDERS
  申请人：The University Of Mississippi

  公开号：EP3102204B1

  公开（公告）日：2021-05-05