ethyl 5-methoxy-2,3-dihydro-1,4-benzodioxin-2-carboxylic ester | 75929-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: ethyl 5-methoxy-2,3-dihydro-1,4-benzodioxin-2-carboxylic ester
• 英文别名: 8-methoxy-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid ethyl ester；Ethyl 5-methoxy-2,3-dihydro-1,4-benzodioxine-3-carboxylate
• CAS: 75929-47-4
• 化学式: C₁₂H₁₄O₅
• 分子量: 238.24
• InChiKey: KEXNOFJIMHTHLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-methoxy-2,3-dihydro-1,4-benzodioxin-2-carboxylic ester 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 (2R)-8-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl-4-methylbenzenesulfonate
  参考文献：
  名称：

  N-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents

  摘要：

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.

  DOI：

  10.1021/jm9910122
• 作为产物：
  描述：

  乙醇 、 8-methoxy-1,4-benzodioxan-2-carboxamide 在 盐酸 作用下， 反应 16.0h， 生成 ethyl 5-methoxy-2,3-dihydro-1,4-benzodioxin-2-carboxylic ester
  参考文献：
  名称：

  N-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents

  摘要：

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.

  DOI：

  10.1021/jm9910122

文献信息

• .alpha.-Adrenoreceptor reagents. 1. Synthesis of some 1,4-benzodioxans as selective presynaptic .alpha.2-adrenoreceptor antagonists and potential antidepressants
  作者：Christopher B. Chapleo、Peter L. Myers、Richard C. M. Butler、John C. Doxey、Alan G. Roach、Colin F. C. Smith

  DOI：10.1021/jm00360a008

  日期：1983.6

  None of these derivatives are as potent or selective as 5, although some do display a degree of selectivity as antagonists. Some derivatives were found to possess agonist properties that, with the exception of 23, favored the postsynaptic site. Compounds 9, 12, 16, 21, 30, and 51 possessing presynaptic alpha 2-adrenoreceptor antagonist and postsynaptic alpha 1-adrenoreceptor partial agonist properties

  讨论了RX 781094，2-（1,4-苯并二恶烷-2-基）-2-咪唑啉盐酸盐（5）的合理设计，该化合物是新型的α2-肾上腺素受体有效和选择性拮抗剂。在突触前α2肾上腺素受体上起拮抗剂作用的化合物可能是有效的新型抑郁症治疗方法，因为它具有增加中央受体部位去甲肾上腺素浓度的能力。已经研究了芳族和咪唑啉环中取代基的作用，以及用examined官能团或其他杂环系统取代咪唑啉环的作用。尽管有些衍生物确实表现出一定程度的拮抗剂，但这些衍生物都不像5那样有效或具有选择性。发现一些衍生物具有激动剂特性，除23种外，它们更有利于突触后位点。化合物9
• BENZIMIDAZOLES AND ANALOGS AS RHO KINASE INHIBITORS
  申请人：Feng Yangbo

  公开号：US20110052562A1

  公开（公告）日：2011-03-03

  Compounds useful as Rho kinase inhibitors according to formula IA or IB: wherein A, B, D, E, R 1 , R 2 and Ar 1 are as defined herein, and any tautomer, salt, stereoisomer, hydrate, solvent, or prodrug thereof, pharmaceutical compositions, methods of treatment, and synthetic methods are provided.

  提供公式IA或IB所示的有用的Rho激酶抑制剂化合物：其中A、B、D、E、R1、R2和Ar1的定义如本文所述，并提供任何互变异构体、盐、立体异构体、水合物、溶剂或前药，以及制药组合物、治疗方法和合成方法。
• New and promising type of leukotriene B4 (LTB4) antagonists based on the 1,4-benzodioxine structure
  作者：Latifa Bouissane、Mostafa Khouili、Gérard Coudert、M. Dolors Pujol、Gérald Guillaumet

  DOI：10.1016/j.ejmech.2023.115332

  日期：2023.6

  allow the development of new types of structures based on 1,4-benzodioxine. Forty-one new 1,4-benzodioxine molecules substituted at different positions of the heterocyclic nucleus were synthesized to determine the minimum structural requirements by studying structure-activity relationships. Eighteen of them were tested in vitro and in vivo for their anti-inflammatory activity related to the antagonist

  新的白三烯 B4 (LTB4) 拮抗剂已被合成，可被视为潜在的抗炎药物。含有 1,4-苯并二恶英双氧化核的结构构成了一组潜在的白三烯 B4 (LTB4) 拮抗剂。本研究的目的是获得有效和选择性的 LTB4 拮抗剂，作为阐明 LTB4 在炎症过程中的作用的一种方式，从而允许开发基于 1,4-苯并二恶英的新型结构。合成了 41 个在杂环核不同位置取代的新 1,4-苯并二恶英分子，通过研究构效关系确定最低结构要求。其中十八个在体外和体内进行了测试因为它们的抗炎活性与 LTB4 的拮抗剂特性有关。药理学试验表明化合物24b、24c和24e具有令人满意的体外活性，IC50 分别为 288、439、477 nM。使用在体外试验24b中表现出更大活性的化合物进行的体内试验的结果显示出显着的抗炎特性。
• Khouili, Mostafa; Souizi, Abdelaziz; Pujol, Ma. Dolors, Scientia Pharmaceutica, 1997, vol. 65, # 1-2, p. 21 - 32
  作者：Khouili, Mostafa、Souizi, Abdelaziz、Pujol, Ma. Dolors、Coudert, Gerard、Guillaumet, Gerald

  DOI：——

  日期：——
• <i>N</i>-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents
  作者：Alan M. Birch、Paul A. Bradley、Julie C. Gill、Frank Kerrigan、Pat L. Needham

  DOI：10.1021/jm9910122

  日期：1999.8.1

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.