2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-indene | 1610700-29-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-indene
• CAS: 1610700-29-2
• 化学式: C₁₁H₁₂ClF
• 分子量: 198.668
• InChiKey: HKUPGOHDZHQGNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)piperazine dihydrochloride 、 2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-indene 在 potassium carbonate 、 potassium iodide 作用下， 以 乙二醇二甲醚 为溶剂， 反应 12.0h， 生成 1-(4-chloro-phenyl)-4-[2-(5-fluoro-indan-2-yl)-ethyl]-piperazine
  参考文献：
  名称：

  Identification of a new selective dopamine D4 receptor ligand

  摘要：

  The dopamine D-4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D-4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD(4) receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D-4 receptor. Compound 27 (KiD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D-4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D-4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT(1A)R and 5HT(2B)R, have binding affinity constants better than 100 nM (K-i < 100 nM). Compound 28 is a potentially useful D-4-selective ligand for probing disease treatments involving the D-4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.04.026
• 作为产物：
  描述：

  2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-inden-1-one 在 盐酸 、 zinc amalgam 作用下， 以 水 、 甲苯 为溶剂， 反应 12.0h， 以90%的产率得到2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-indene
  参考文献：
  名称：

  5-HT 1A和5-HT 7双受体配体的设计与合成

  摘要：

  5-HT 1A和5-HT 7受体最近成为讨论的中心，部分原因是它们在主要中枢神经系统疾病（例如抑郁症，睡眠障碍和精神分裂症）的病因学中的重要作用。作为我们为这些受体确定双重靶向配体的研究的一部分，我们对选择性5HT 7受体配体进行了系统修饰，最终鉴定了几个双重5-HT 1A和5-HT 7受体配体。化合物16是四氢异喹啉（THIQ）的丁酮衍生物，被认为是对两种受体均具有低纳摩尔摩尔亲和力的最有效药物。有趣的是，化合物16对其他临床相关的多巴胺受体也显示出中等亲和力。因此，可以预料，在我们寻找具有治疗中枢神经系统疾病潜力的新配体的过程中，化合物16可以作为进一步开发的先导。

  DOI：

  10.1016/j.bmc.2016.05.053

文献信息

• ALKYLATED TETRAHYDROISOQUINOLINES FOR BINDING TO CENTRAL NERVOUS SYSTEM RECEPTORS
  申请人：Florida A&M University

  公开号：US20180193330A1

  公开（公告）日：2018-07-12

  Derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ) having the general formula A-(CH 2 ) n —B are provided, wherein A is THIQ or a substituted derivative thereof and B is an aryl, cycloalkylaryl, or cycloalkyl group, wherein A and B are linked to each other by an alkyl or substituted alkyl chain. The compounds are useful as selective ligands (agonists or antagonists) of central nervous system receptors, and in particular of the seratonin receptors. The compounds or their salts can be formulated into pharmaceutical in need thereof by any route of administration suitable for a desired treatment protocol and especially for the treatment of psychiatric disorders.

  1,2,3,4-四氢异喹啉（THIQ）的衍生物具有一般公式A-(CH2)n—B，其中A是THIQ或其取代衍生物，B是芳基、环烷基芳基或环烷基基团，其中A和B通过烷基或取代烷基链相连。这些化合物可用作中枢神经系统受体的选择性配体（激动剂或拮抗剂），特别是血清素受体的配体。这些化合物或其盐可以通过适合所需治疗方案的任何给药途径制成药物，特别适用于治疗精神障碍。
• New analogs of SYA013 as sigma-2 ligands with anticancer activity
  作者：Gladys Asong、Xue Y. Zhu、Barbara Bricker、Terrick Andey、Felix Amissah、Nazarius Lamango、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2019.04.012

  日期：2019.6

  moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1 for evaluation in several solid tumor cell lines. In addition, we have synthesized new analogs of 1 and now report that several of them bind preferentially at the sigma-2 receptor and have shown inhibition of several cancer cell lines

  我们先前的研究表明4-（4-（4-氯苯基）-1,4-二氮杂-1-基）-1-（4-氟苯基）丁-1--1-酮·2HCl（SYA013）1为sigma配体对sigma-2受体具有中等选择性。鉴于实体肿瘤中sigma受体的过表达以及具有抗癌活性的sigma配体的报道，我们选择1在几种实体瘤细胞系中进行评估。此外，我们合成了1的新类似物，现在报道其中一些类似物优先与sigma-2受体结合，并显示出对多种癌细胞系（包括MDA-MB-231，MDA-MB-486，A549，PC）的抑制作用-3，MIA PaCa-2和Panc-1细胞。特别地，化合物1和12已显示出对Panc-1细胞系的亚微摩尔活性。还发现这些化合物中的几种对癌细胞具有选择性毒性，