2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-inden-1-one | 1366349-29-2

• 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-inden-1-one
• 英文别名: 2-(2-chloro-ethyl)-5-fluoro-indan-1-one；2-(2-Chloroethyl)-5-fluoro-2,3-dihydroinden-1-one；2-(2-chloroethyl)-5-fluoro-2,3-dihydroinden-1-one
• CAS: 1366349-29-2
• 化学式: C₁₁H₁₀ClFO
• 分子量: 212.651
• InChiKey: QCSSORBIOJVBFO-UHFFFAOYSA-N

物化性质

• 沸点：
  325.2±35.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 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：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-inden-1-one 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙二醇二甲醚 、 甲苯 为溶剂， 反应 64.0h， 生成 2-{2-[4-(4-chlorophenyl)-[1,4]diazepan-1-yl]-ethyl}-5-fluoro-indan-1-one ethylene acetal
  参考文献：
  名称：

  Structure–activity relationship studies of SYA 013, a homopiperazine analog of haloperidol

  摘要：

  Structure-activity relationship studies on 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl) butan-1-one (SYA 013), a homopiperazine analog of haloperidol has resulted in an understanding of the effect of structural modifications on binding affinity at dopamine and serotonin receptor subtypes. Further exploration, using bioisosteric replacement strategies has led to the identification of several new agents including compounds 7, 8, 11 and 12 which satisfy the initial criteria for further exploration as new antipsychotic agents. In addition, compound 18, a D-3 selective tropanol, has been identified as having the potential for further optimization into a useful drug which may combat neuropsychiatric diseases. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.01.022
• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 在 硫酸 、 乙酸酐 作用下， 反应 17.0h， 生成 2-(2-chloroethyl)-5-fluoro-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  Structure–activity relationship studies of SYA 013, a homopiperazine analog of haloperidol

  摘要：

  Structure-activity relationship studies on 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl) butan-1-one (SYA 013), a homopiperazine analog of haloperidol has resulted in an understanding of the effect of structural modifications on binding affinity at dopamine and serotonin receptor subtypes. Further exploration, using bioisosteric replacement strategies has led to the identification of several new agents including compounds 7, 8, 11 and 12 which satisfy the initial criteria for further exploration as new antipsychotic agents. In addition, compound 18, a D-3 selective tropanol, has been identified as having the potential for further optimization into a useful drug which may combat neuropsychiatric diseases. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.01.022

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 dual 5-HT1A and 5-HT7 receptor ligands derived from SYA16263
  作者：Edward Ofori、Edem K. Onyameh、Uma M. Gonela、Chandrashekhar Voshavar、Barbara Bricker、Tracy L. Swanson、Amy J. Eshleman、Jennifer L. Schmachtenberg、Shelley H. Bloom、Aaron J. Janowsky、Seth Y. Ablordeppey

  DOI：10.1016/j.ejmech.2021.113243

  日期：2021.3

  nM). Thus, it was of interest to exploit its pharmacophore elements in designing new dual receptor ligands. Using SYA16263 as the lead molecule, we have conducted a limited structure-affinity relationship (SAFIR) study by modifying various structural elements in the arylalkyl moiety, resulting in the identification of a new dual 5-HT1AR and 5-HT7R ligand, 6-chloro-2-methyl-2-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)-2

  我们之前曾报道，双重 5-HT 1A和 5-HT 7受体配体可能会发现作为各种 CNS 相关疾病（包括认知和抗焦虑障碍）的治疗选择。我们最近还报道了 SYA16263 具有抗精神病药样特性，在动物模型中没有僵直症，这归因于其将 β-抑制蛋白募集到 D 2受体的能力。然而，SYA16263 也以非常高的亲和力与 5-HT 1A R ( Ki = 1.1 nM) 结合，在 5-HT 7 R ( Ki= 90纳米）。因此，在设计新的双受体配体中利用其药效团元素是有意义的。使用 SYA16263 作为先导分子，我们通过修饰芳烷基部分中的各种结构元素进行了有限结构亲和关系 (SAFIR) 研究，从而鉴定出新的双 5-HT 1A R 和 5-HT 7 R 配体, 6-chloro-2-methyl-2-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)-2,3-dihydro-1H-inden-1-one
• Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands
  作者：Edward Ofori、Xue Y. Zhu、Jagan R. Etukala、Kwakye Peprah、Kamanski R. Jordan、Adia A. Adkins、Barbara A. Bricker、Hye J. Kang、Xi-Ping Huang、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2016.05.053

  日期：2016.8

  5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7 receptor ligand culminating in the identification

  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。
• 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，