2-(2-chloroethyl)-indan-1-one | 1610700-28-1

• 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)-indan-1-one
• 英文别名: 2-(2-chloroethyl)-2,3-dihydro-1H-inden-1-one；2-(2-Chloroethyl)-2,3-dihydroinden-1-one
• CAS: 1610700-28-1
• 化学式: C₁₁H₁₁ClO
• 分子量: 194.661
• InChiKey: HGEOKGVLGMQHLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(2-chloroethyl)-indan-1-one 在 potassium carbonate 、 对甲苯磺酸 、 potassium iodide 作用下， 以 乙二醇二甲醚 、 甲苯 为溶剂， 反应 73.0h， 生成 2-{2-[4-(4-chlorophenyl)-piperazin-1-yl]-ethyl}indan-1-one
  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：

  4-氯苯丁酮 在 硫酸 、 乙酸酐 作用下， 反应 19.0h， 生成 2-(2-chloroethyl)-indan-1-one
  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

文献信息

• Synthesis and evaluation of the structural elements in alkylated tetrahydroisoquinolines for binding to CNS receptors
  作者：Edward Ofori、Xue Y. Zhu、Jagan R. Etukala、Barbara A. Bricker、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2016.09.019

  日期：2016.11

  complex and involve multiple receptor systems and thus, the treatment options for these diseases must focus on targeting the multiple receptors implicated in the various disorders. Schizophrenia and depression are examples of such diseases and their pharmacotherapy thus depends on agents which target multiple receptors including the dopamine, serotonin and even cholinergic receptors at the same time. In our

  中枢神经系统疾病通常很复杂，涉及多个受体系统，因此，这些疾病的治疗方案必须集中于针对与各种疾病有关的多个受体。精神分裂症和抑郁症是此类疾病的例子，因此它们的药物治疗取决于同时靶向多种受体的药物，包括多巴胺、血清素甚至胆碱能受体。在我们之前寻找多受体配体的活动中，我们已确定苯并噻唑1a作为初始先导分子。在目前的工作中，我们扩展了1a的结构亲和关系 (SAFIR) ，从而鉴定出部分抑制的丁酰苯3j作为有效且选择性的双 5-HT 1A和 5-HT 7受体配体。预计化合物3j可以作为我们寻找具有治疗 CNS 起源疾病潜力的新型配体的进一步开发的新先导。
• 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，