Ethyl 5-methanesulphonylindole-2-carboxylate | 220679-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Ethyl 5-methanesulphonylindole-2-carboxylate
• 英文别名: Ethyl 5-(methylsulfonyl)-1H-indole-2-carboxylate；ethyl 5-methylsulfonyl-1H-indole-2-carboxylate
• CAS: 220679-12-9
• 化学式: C₁₂H₁₃NO₄S
• 分子量: 267.306
• InChiKey: BWJQKKTWLJTDSF-UHFFFAOYSA-N

物化性质

• 沸点：
  510.4±43.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 5-methanesulphonylindole-2-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 锂硼氢 、 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.25h， 生成 [3-(6-Methoxypyridin-3-yl)-5-methylsulfonyl-1-[[3-(trifluoromethoxy)phenyl]methyl]indol-2-yl]methanol
  参考文献：
  名称：

  Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354

  摘要：

  Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was found to have an IC50 of 140nM for PAR-4 with 71-fold selectivity versus PAR-1 (PAR-1IC50=10μM).

  DOI：

  10.1016/j.bmcl.2014.08.021

文献信息

• Structure–Activity Relationship (SAR) Development and Discovery of Potent Indole-Based Inhibitors of the Hepatitis C Virus (HCV) NS5B Polymerase
  作者：Kevin X. Chen、Bancha Vibulbhan、Weiying Yang、Mousumi Sannigrahi、Francisco Velazquez、Tin-Yau Chan、Srikanth Venkatraman、Gopinadhan N. Anilkumar、Qingbei Zeng、Frank Bennet、Yueheng Jiang、Charles A. Lesburg、Jose Duca、Patrick Pinto、Stephen Gavalas、Yuhua Huang、Wanli Wu、Oleg Selyutin、Sony Agrawal、Boris Feld、Hsueh-Cheng Huang、Cheng Li、Kuo-Chi Cheng、Neng-Yang Shih、Joseph A. Kozlowski、Stuart B. Rosenblum、F. George Njoroge

  DOI：10.1021/jm201258k

  日期：2012.1.26

  Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2, extensive SAR studies were performed at different positions of the indole core. The best C-5 groups were found to be compact and nonpolar moieties and that the C-6 attachments were not affecting potency. Limited N-1 benzyl-type substituent studies indicated that the best substitutions were fluoro or methyl groups at 2' or 5' positions of the benzyl group. To improve pharmacokinetic (PK) properties, acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the identification of compound 56, which had an excellent potency in both NS5B enzyme (IC50 = 0.008 mu M) and cell-based replicon (EC50 = 0.02 mu M) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 mu M.h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported.
• The discovery of novel indole-2-carboxamides as cannabinoid CB1 receptor antagonists
  作者：Phillip M. Cowley、James Baker、David R. Barn、Kirsteen I. Buchanan、Ian Carlyle、John K. Clark、Thomas R. Clarkson、Maureen Deehan、Darren Edwards、Richard R. Goodwin、David Jaap、Yasuko Kiyoi、Chris Mort、Ronald Palin、Alan Prosser、Glenn Walker、Nick Ward、Grant Wishart、Trevor Young

  DOI：10.1016/j.bmcl.2010.10.104

  日期：2011.1

  The discovery and structure-activity relationship of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB1 receptor is disclosed. Compound 26i was found to be a high potency, selective cannabinoid CB1 antagonist. (C) 2010 Elsevier Ltd. All rights reserved.
• N-Benzylindole-2-carboxylic acids: potent functional antagonists of the CCR2b chemokine receptor
  作者：Jason G. Kettle、Alan W. Faull、Andy J. Barker、D.Huw Davies、Michael A. Stone

  DOI：10.1016/j.bmcl.2003.10.049

  日期：2004.1

  Screening of the corporate database led to the discovery of a novel series of N-benzylindole-2-carboxylic acid CCR2b chemokine receptor antagonists. These compounds demonstrate high affinity and functional inhibition of the CCR2b receptor. A discussion of the structure-activity relationships is presented, together with evidence for a highly selective receptor binding profile. (C) 2003 Elsevier Ltd. All rights reserved.
• A concise synthesis of 3-hydroxyindole-2-carboxylates by a modified Baeyer–Villiger oxidation
  作者：Zachary L. Hickman、Claudio F. Sturino、Nicolas Lachance

  DOI：10.1016/s0040-4039(00)01456-8

  日期：2000.10

  Indole-2-carboxylates are converted in good yields to 3-hydroxyindole-2-carboxylates by use of a Vilsmeier-Haack/Baeyer-viIliger reaction sequence. A systematic examination of the various indole substituents revealed this route to be general in scope. (C) 2000 Published by Elsevier Science Ltd.
• INDOLE DERIVATIVES AND THEIR USE AS MCP-1 ANTAGONISTS
  申请人：AstraZeneca AB

  公开号：EP1003504B1

  公开（公告）日：2003-07-02