2-amino-6-(2'-spiro[1',3']dioxolane)-6,7-dihydro-4H-benzo[b]thiophen-3-carboxylic acid ethyl ester | 173032-58-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-amino-6-(2'-spiro[1',3']dioxolane)-6,7-dihydro-4H-benzo[b]thiophen-3-carboxylic acid ethyl ester
• 英文别名: 2-amino-1,4-dioxaspiro[6.6]4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester；ethyl 2-amino-5,7-dihydro-4H-spiro[benzo[b]thiophene-6,2'-[1,3]dioxolane]-3-carboxylate；ethyl 2-amino-4,7-dihydro-5H-spiro[1-benzothiophene-6,2'-[1,3]dioxolane]-3-carboxylate；Ethyl 2-Amino-6,6-ethylenedioxy-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate；Ethyl 2-amino-4,7-dihydro-5H-spiro[1-benzothiophere-6,2'-[1,3]dioxolane]-3-carboxylate；ethyl 2'-aminospiro[1,3-dioxolane-2,6'-5,7-dihydro-4H-1-benzothiophene]-3'-carboxylate
• CAS: 173032-58-1
• 化学式: C₁₃H₁₇NO₄S
• 分子量: 283.348
• InChiKey: HATAXVHWNRVHSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-6-(2'-spiro[1',3']dioxolane)-6,7-dihydro-4H-benzo[b]thiophen-3-carboxylic acid ethyl ester 在 sodium tetrahydroborate 、 TEA 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 2-(ethoxyoxalylamino)-6-hydroxy-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery and SAR of a Novel Selective and Orally Bioavailable Nonpeptide Classical Competitive Inhibitor Class of Protein-Tyrosine Phosphatase 1B

  摘要：

  Reversible phosphorylation and dephosphorylation of key proteins on tyrosine residues are important parts of intracellular signaling triggered by hormones and other agents. Recent knock-out studies in mice have identified PTP1B as a potential target for the treatment of diabetes and obesity. As a consequence, a number of academic and industrial groups are aggressively pursuing the development of selective PTP1B inhibitors. In addition, other protein-tyrosine phosphatases (PTPs) appear to be critically involved in major diseases such as cancer and autoimmunity. Given the diversity of PTPs and their potential as drug targets in different diseases, we have taken a broad approach to develop active site-directed selective inhibitors of specific members of this family of enzymes. Using a high throughput screening, we have previously identified 2-(oxalylamino)benzoic acid 3a as a relatively weak but classical competitive inhibitor of several PTPs.(4) On the basis of our early studies, indicating that 3a might be used as a starting point for the synthesis of selective PTP inhibitors, we now present our efforts in expansion of this concept and provide here a number of new chemical scaffolds for the development of inhibitors of different members of the PTP family. Although the core structure of these inhibitors is charged, good oral bioavailability has been observed in rat for some compounds. Furthermore, we have observed enhancement of 2-deoxy-glucose accumulation in C2C12 cells with prodrug analogues.

  DOI：

  10.1021/jm0209026
• 作为产物：
  描述：

  1,4-环己二酮单乙二醇缩酮 、 氰乙酸乙酯 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-amino-6-(2'-spiro[1',3']dioxolane)-6,7-dihydro-4H-benzo[b]thiophen-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  发现新型（4-哌啶基）-哌嗪作为有效的和口服活性的乙酰辅酶A羧化酶1/2非选择性抑制剂：F-Boc和triF-Boc基团是Boc基团的酸稳定生物等位基因

  摘要：

  合成了新型（4-哌啶基）-哌嗪衍生物，并将其评估为ACC1 / 2非选择性抑制剂。哌啶环氮上取代基的优化导致了氟取代的叔丁氧羰基的鉴定。高级类似物1，，1,1-三氟-2-甲基丙烷-2-基4- {4-[（（2-氨基-6-甲基-1-苯并噻吩-3-基）羰基]哌嗪-1-基}哌啶-1-羧酸盐（12c）在酶测定和基于细胞的测定中显示出有效的抑制活性。口服给药后，化合物12c还表现出大鼠肝新脂肪酸合成的减少。

  DOI：

  10.1016/j.bmc.2011.01.041

文献信息

• NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
  申请人：Carroll William A.

  公开号：US20090018114A1

  公开（公告）日：2009-01-15

  The present application relates to cannabinoid receptor ligands containing compounds of formula (I) wherein A, R 1 , R 2 , and R 3 are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

  本申请涉及含有式(I)化合物的大麻素受体配体，其中A、R1、R2和R3如规范中所定义。本申请还涉及包含这种化合物的组合物，以及使用这种化合物和组合物治疗疾病和疾病的方法。
• New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds
  作者：Gábor Szántó、Attila Makó、Imre Bata、Bence Farkas、Sándor Kolok、Mónika Vastag、Attila Cselenyák

  DOI：10.1016/j.bmcl.2016.07.009

  日期：2016.8

  human P2X3 receptor antagonist compound that can penetrate the central nervous system, the compound collection of Gedeon Richter was screened. A hit series of tricyclic compounds was subjected to a rapid, two-step optimization process focusing on increasing potency, improving metabolic stability and CNS penetrability. Attempts resulted in compound 65, a potential tool compound for testing P2X3 inhibitory

  嘌呤能P2X3受体是三聚体配体门控离子通道，其拮抗作用是吸引人的但具有挑战性且尚未得到充分验证的药物开发构想。为了鉴定可穿透中枢神经系统的口服活性，有效的人P2X3受体拮抗剂化合物，筛选了Gedeon Richter的化合物集合。对命中的三环化合物系列进行了快速的两步优化过程，重点是提高效力，改善代谢稳定性和CNS渗透性。尝试产生了化合物65，这是一种用于在体内测试P2X3抑制作用的潜在工具化合物。
• Use of src SH2 specific compounds to treat a bone resorption disease
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0727211A1

  公开（公告）日：1996-08-21

  Invented is a method of treating a bone resorption disease in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human src SH2 domain with a binding affinity greater than fifty-fold higher than the binding affinity with which the compound binds to a human lck SH2 domain and a human fyn SH2 domain, and, binds to a human hcp SH2 domain, a human Grb2 SH2 domain, a human SH-PTP2 SH2 domain and a human p85 SH2 domain with a binding affinity which is greater than fifty-fold lower than the binding affinity with which the compound binds to such src SH2 domain.

  已发明一种治疗骨吸收疾病的方法，包括向受试者施用与人src SH2结构域结合的化合物的治疗有效量，其结合亲和力比其与人lck SH2结构域和人fyn SH2结构域结合的结合亲和力高出五十倍以上，并且与人hcp SH2结构域、人Grb2 SH2结构域、人SH-PTP2 SH2结构域和人p85 SH2结构域结合的结合亲和力比其与该src SH2结构域结合的结合亲和力低五十倍以上。
• [EN] SUBSTITUTED TETRAHYDROBENZOTHIENOPYRIMIDINAMINE COMPOUNDS USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS<br/>[FR] COMPOSES TETRAHYDROBENZOTHIENOPYRIMIDINAMINE A SUBSTITUTION UTILES POUR LE TRAITEMENT DE TROUBLES HYPER-PROLIFERATIFS
  申请人：BAYER PHARMACEUTICALS CORP

  公开号：WO2005010008A1

  公开（公告）日：2005-02-03

  The present invention relates to a compound of Formula (I) and its use in treating hyper-proliferative disorders.

  这项发明涉及一种式（I）化合物及其在治疗高增殖性疾病中的用途。
• An Efficient One-Pot Synthesis of Substituted 2-Aminothiophenes via Three-Component Gewald Reaction Catalyzed by l-Proline
  作者：Xiao-Yong Xu、Bu-Bing Zeng、Tao Wang、Xian-Gui Huang、Jia Liu、Bo Li、Jin-Jin Wu、Kai-Xian Chen、Wei-Liang Zhu

  DOI：10.1055/s-0029-1219917

  日期：2010.6

  An efficient one-pot procedure for the direct catalytic synthesisof substituted 2-aminothiophenes catalyzed by L-proline undermild reaction conditions has been developed. A variety of functionalized2-aminothiophene scaffolds were assembled in high yields by thiscatalytic protocol. Low catalyst loading, simple procedure, andhigh yields are the important attributes of this methodology.

  已开发出一种在温和反应条件下由 L-脯氨酸催化直接催化合成取代 2-氨基噻吩的有效一锅法。通过该催化方案以高产率组装了多种功能化的2-氨基噻吩支架。低催化剂负载、简单程序和高产率是该方法的重要属性。