ethyl thieno[2’,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate | 27035-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: ethyl thieno[2’,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate
• 英文别名: Aethyl-5,6-methylendioxybenzothiophen-2-carboxylat；ethyl 5,6-methylenedioxylbenzo[b]thiophene-2-carboxylate；Ethyl thieno[2,3-f][1,3]benzodioxole-6-carboxylate
• CAS: 27035-40-1
• 化学式: C₁₂H₁₀O₄S
• 分子量: 250.275
• InChiKey: DTJWYHCMYXXXGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  73
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl thieno[2’,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate 在 sodium hydride 、 二甲基亚砜 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 0.5h， 生成 1-(5,6-methylenedioxylbenzo[b]thiophen-2-yl)-2-(methylsulfinyl)ethanone
  参考文献：
  名称：

  新型取代苯并噻吩或苯并呋喃衍生物作为BMP-2上调剂的合成及其对BMP-2上调作用的评价及对糖皮质激素引起的大鼠骨质疏松的影响

  摘要：

  BMP途径是设计用于治疗低骨量的治疗剂的有希望的新目标。为了丰富我们对SAR的理解，并基于我们先前得出的结构效应关系，在这项工作中准备了23种衍生物。提出了这些化合物在糖皮质激素诱导的骨质疏松症大鼠中的合成，上调其BMP-2表达的活性以及预防骨丢失的功效。通过光学显微镜评估所测试的大鼠的骨组织学表明，化合物1，21，35，和与模型组相比，38显著增加了小梁，以及与治疗的组的小梁8A与雷洛昔芬和阿法骨化醇相似。该化合物显示出发展为同化剂的潜力。

  DOI：

  10.1016/j.ejmech.2015.04.016
• 作为产物：
  描述：

  6-硝基胡椒醛 、 巯基乙酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 ethyl thieno[2’,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate
  参考文献：
  名称：

  新型取代苯并噻吩或苯并呋喃衍生物作为BMP-2上调剂的合成及其对BMP-2上调作用的评价及对糖皮质激素引起的大鼠骨质疏松的影响

  摘要：

  BMP途径是设计用于治疗低骨量的治疗剂的有希望的新目标。为了丰富我们对SAR的理解，并基于我们先前得出的结构效应关系，在这项工作中准备了23种衍生物。提出了这些化合物在糖皮质激素诱导的骨质疏松症大鼠中的合成，上调其BMP-2表达的活性以及预防骨丢失的功效。通过光学显微镜评估所测试的大鼠的骨组织学表明，化合物1，21，35，和与模型组相比，38显著增加了小梁，以及与治疗的组的小梁8A与雷洛昔芬和阿法骨化醇相似。该化合物显示出发展为同化剂的潜力。

  DOI：

  10.1016/j.ejmech.2015.04.016

文献信息

• 苯并五元不饱和杂环类化合物或其药用盐及其 制备方法、药物组合物及其应用
  申请人：中国医学科学院医药生物技术研究所

  公开号：CN103130705B

  公开（公告）日：2016-04-20

  本发明提供了具有如通式I所示结构的苯并五元不饱和杂环化合物或其药用盐及其制备方法、药物组合物及其应用。实验表明，本发明所述的化合物具有上调骨形成蛋白BMP-2表达活性，抗体内抗骨质疏松作用，并具有改善SAMP6小鼠骨质疏松症状的效果；体外活性测试显示，本发明化合物表现出对骨形态发生蛋白BMP-2表达的明显上调作用。
• [EN] MODULATORS FOR NICOTINIC ACETYLCHOLINE RECEPTOR α2 AND α4 SUBUNITS<br/>[FR] MODULATEURS POUR LES SOUS-UNITÉS Α2 ET Α4 DE RÉCEPTEUR NICOTINIQUE DE L'ACÉTYLCHOLINE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2016191366A1

  公开（公告）日：2016-12-01

  Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs, but is without effect on α3* or α6* nAChRs ("*" indicates presence of other nAChR subunits). Br-BPTC binds to the C-terminal extracellular sequences of a4 subunits, which is also a PAM site for steroid hormone estrogens such as 17-β estradiol. Br-PBTC is much more potent than estrogens. Like 17-P-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more a4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Various bioactive analogs of Br-PBTC are provided.

  正向变构调节剂（PAMs）对尼古丁乙酰胆碱受体（nAChR）是重要的治疗候选药物，同时也是有价值的研究工具。我们发现了一种新型II型PAM，(R)-7-溴-N-(哌啶-3-基)苯并[b]噻吩-2-甲酰胺（Br-PBTC），它既增加了激活，又重新激活了脱敏的nAChRs。这种化合物增加了α2*和α4* nAChRs对乙酰胆碱的响应，但对α3*或α6* nAChRs没有影响（"*"表示存在其他nAChR亚基）。Br-BPTC结合到α4亚基的C端外胞外序列，这也是类固醇激素雌激素如17-β雌二醇的PAM位点。Br-PBTC比雌激素更有效。与17-β雌二醇一样，非类固醇Br-PBTC只需要一个α4亚基来增强nAChR功能，并且随着更多的α4亚基，其增强作用更强。这个特性使Br-BPTC能够增强(α4β2)(α6β2)β3而不是(α6β2)2β3 nAChRs的激活。提供了各种生物活性类似物的Br-PBTC。
• Substituted Benzothiophene or Benzofuran Derivatives as a Novel Class of Bone Morphogenetic Protein-2 Up-Regulators: Synthesis, Structure−Activity Relationships, and Preventive Bone Loss Efficacies in Senescence Accelerated Mice (SAMP6) and Ovariectomized Rats
  作者：Hui-fang Guo、Hua-yi Shao、Zhao-yong Yang、Si-tu Xue、Xue Li、Zong-ying Liu、Xiao-bo He、Jian-dong Jiang、Yue-qin Zhang、Shu-yi Si、Zhuo-rong Li

  DOI：10.1021/jm901685n

  日期：2010.2.25

  In this work, substituted benzothiophene and benzofuran compounds were found to be a new class of potential anabolic agents by enhancing BMP-2 expression. A series of benzothiophene and benzofuran derivatives have been synthesized, and their activities of up-regulating BMP-2 and bone loss prevention efficacies in SAMP6 mice and OVX rats have been studied. Benzothiophenes 1, 3, 14, 4a, 7a, 8a, and benzofuran analogue 2 showed higher BMP-2 up-regulation rates in vitro. Compound 8111 was found to significantly affect the bone formation rate of tested SAMP6 mice. Compound I showed an improved bone quality in SAMP6 mice and also showed activity in OVX rats. We have demonstrated that Substituted benzothiophene and benzofuran derivatives, especially compounds I and 8a, enhance BMP-2 expression in vitro and in vivo and stimulate bone formation and trabecular connectivity restoration ill vivo. The compounds represent potential leads in the development of a new class of anabolic agents.
• Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties
  作者：Si-tu Xue、Lei Zhang、Zhuo-song Xie、Jie Jin、Hui-Fang Guo、Hong Yi、Zong-ying Liu、Zhuo-rong Li

  DOI：10.1016/j.ejmech.2020.112465

  日期：2020.8

  The bone morphogenetic protein (BMP) pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. This study optimized the structure of the anti-osteoporosis compound 38 by balancing its lipophilicity and improving its stability. Twenty derivatives which were not reported in the literature were designed and synthesized. The ovariectomized rat model of osteoporosis was selected to evaluate the therapeutic effects. Compound 125 showed better therapeutic efficacy than that of 38. We verified the anti-osteoporosis activity and BMP-2 protein upregulation after treatment with 125 in a zebrafish osteoporosis model. We found that 125 improved the ADME properties, therapeutic efficacy, and pharmacokinetics of the drug. Overall, we evaluated the anti-osteoporosis effects of the compounds of this type, preliminarily determined the target patient population, verified the mechanism of action, clarified the level of toxicity, and provided preliminary ADME data. We believe that these compounds can both correct bone loss that is already occurring in patients and have broad clinical applicability. (C) 2020 Elsevier Masson SAS. All rights reserved.
• [EN] BENZO 5-MEMBERED UNSATURATED HETEROCYCLIC COMPOUNDS AND PREPARATION METHODS THEREOF<br/>[FR] COMPOSÉS DE BENZO HÉTÉROCYCLIQUES INSATURÉS À 5 ÉLÉMENTS ET PROCÉDÉS POUR LES PRÉPARER
  申请人：INST MED BIOTECHNOLOGY CAMS

  公开号：WO2012068702A1

  公开（公告）日：2012-05-31

  Disclosed are benzo 5-membered unsaturated heterocyclic compounds represented by formula I and their pharmaceutically acceptable salts, preparation methods and uses thereof in the preparation of the drugs for treating osteoporosis, wherein each substituent of formula (I) is defined as the description.