methyl 6-(methylsulfanyl)-1H-indole-2-carboxylate | 202584-20-1

• 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: methyl 6-(methylsulfanyl)-1H-indole-2-carboxylate
• 英文别名: methyl 6-methylsulfanyl-1H-indole-2-carboxylate
• CAS: 202584-20-1
• 化学式: C₁₁H₁₁NO₂S
• mdl: MFCD06653517
• 分子量: 221.28
• InChiKey: WIDPUEXDDQAFTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6-(methylsulfanyl)-1H-indole-2-carboxylate 在 Oxone 、 lithium hydroxide 、 草酰氯 、 氨 、 N,N-二甲基甲酰胺 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成 3-(2-chlorophenyl)sulfanyl-6-methylsulfonyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors

  摘要：

  The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6-methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.075
• 作为产物：
  描述：

  methyl-2-azido-3-(4-methylthio-phenyl)propenoate 在 dichloromethane hexane 作用下， 以 邻二甲苯 为溶剂， 反应 20.0h， 以to give 11.2 g (61.0%) of methyl-6-methylsulfanyl-1H-indole-2-carboxylate的产率得到methyl 6-(methylsulfanyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Substituted pyrroles

  摘要：

  公式I的化合物，其中R1和R1'分别独立地为烷基、芳基、烯基或炔基；R2和R2'分别独立地为氢、烷基、芳基烷基、烷氧基烷基、羟基烷基、卤代烷基、氨基烷基、单烷基氨基烷基、二烷基氨基烷基、酰胺基烷基、烷基磺酰胺基烷基、芳基磺酰胺基烷基、巯基烷基、烷基硫基烷基、羧基烷基、烷氧羰基烷基、氨基羰基烷基、烷基硫基或烷基亚砜基；R4、R5、R6、R7、R4'、R5'、R6'和R7'各自独立地为氢、CO2R9、CH2OR10、CHO、CH2NR11R12、CON（R13）2、卤素、氰基、芳基、烷基、羟基、烷氧基、芳氧基、卤代烷基、硝基、氨基、芳基氧基、酰胺基、单烷基氨基、二烷基氨基、硫基、烷基、烷基亚砜基、烷基磺酰基、芳基磺酰基、偶氮基、磷酸酯或膦酸盐，但要求R4、R5、R6和R7中至少有一个以及R4'、R5'、R6'和R7'中至少有一个不是氢，但如果R6是甲氧基，则R5或R5'不是甲氧基；R8为烷基或芳基；R9为烷基或芳基；R10为氢、烷基或芳基；R11和R12独立地为氢、烷基、芳基、芳基烷基或酰基；R13为氢、烷基、芳基或芳基烷基；X和Y中的一个表示O，另一个表示O、S、（H，OH）或（H，H）；以及公式I的酸性化合物的药物可接受的前药或与酸性化合物的药物可接受的盐和/或与公式I的碱性化合物的药物可接受的盐是抗增殖剂，可用于治疗癌症。

  公开号：

  US06228877B1

文献信息

• Substituted pyrroles
  申请人：Hoffmann-La Roche Inc.

  公开号：US05891901A1

  公开（公告）日：1999-04-06

  Compounds of the formula ##STR1## wherein R is alkyl, alkylthio or hydroxy, as well as, pharmaceutically acceptable salts of compounds of formula I are antiproliferative agents useful in the treatment of cancer.

  式I的化合物，其中R是烷基、烷硫基或羟基，以及式I化合物的药用可接受盐是抗增殖剂，用于治疗癌症。
• Indole derivatives as anti-inflammatory agents
  申请人：——

  公开号：US20030130337A1

  公开（公告）日：2003-07-10

  This invention relates to compounds, which are generally anti-inflammatory and analgesic compounds, and which are represented by Formula I: 1 wherein A is a —CH 2 —, —O—, —S—, or —S(O)—; and the other substituents are as defined in the specification; or individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents

  本发明涉及一类化合物，通常为抗炎和镇痛化合物，其由以下式I表示：其中A为—CH2—、—O—、—S—或—S(O)—；其他取代基如规范中定义；或其个别异构体、异构体混合物和其药用可接受盐。该发明还涉及含有这类化合物的药物组合物以及它们作为治疗剂的使用方法。
• [EN] INDOLE DERIVATIVES AS COX II INHIBITORS<br/>[FR] DERIVES D'INDOLE UTILES COMME INHIBITEURS DE COX II
  申请人：HOFFMANN LA ROCHE

  公开号：WO2003029212A1

  公开（公告）日：2003-04-10

  This present invention relates to indole derivatives of Formula (I); wherein A, Ar and R1 to R4 are as defines in the specification. The compounds are useful as a selective COX-II inhibitor and, therefore, may be used for the treatment of COX-II mediated diseases.

  本发明涉及公式（I）中的吲哚衍生物；其中A、Ar和R1至R4如规范中所定义。这些化合物可用作选择性COX-II抑制剂，因此可用于治疗COX-II介导的疾病。
• Development of Novel Small-Molecule Activators of Pyruvate Kinase Muscle Isozyme 2, PKM2, to Reduce Photoreceptor Apoptosis
  作者：Thomas J. Wubben、Sraboni Chaudhury、Brennan T. Watch、Jeanne A. Stuckey、Eric Weh、Roshini Fernando、Moloy Goswami、Mercy Pawar、Jason C. Rech、Cagri G. Besirli

  DOI：10.3390/ph16050705

  日期：——

  Treatment options are lacking to prevent photoreceptor death and subsequent vision loss. Previously, we demonstrated that reprogramming metabolism via the pharmacologic activation of PKM2 is a novel photoreceptor neuroprotective strategy. However, the features of the tool compound used in those studies, ML-265, preclude its advancement as an intraocular, clinical candidate. This study sought to develop the next generation of small-molecule PKM2 activators, aimed specifically for delivery into the eye. Compounds were developed that replaced the thienopyrrolopyridazinone core of ML-265 and modified the aniline and methyl sulfoxide functional groups. Compound 2 demonstrated that structural changes to the ML-265 scaffold are tolerated from a potency and efficacy standpoint, allow for a similar binding mode to the target, and circumvent apoptosis in models of outer retinal stress. To overcome the low solubility and problematic functional groups of ML-265, compound 2’s efficacious and versatile core structure for the incorporation of diverse functional groups was then utilized to develop novel PKM2 activators with improved solubility, lack of structural alerts, and retained potency. No other molecules are in the pharmaceutical pipeline for the metabolic reprogramming of photoreceptors. Thus, this study is the first to cultivate the next generation of novel, structurally diverse, small-molecule PKM2 activators for delivery into the eye.

  目前还缺乏防止光感受器死亡及随后视力丧失的治疗方案。在此之前，我们已经证明，通过药物激活 PKM2 来重塑新陈代谢是一种新型的光感受器神经保护策略。然而，这些研究中使用的工具化合物 ML-265 的特性使其无法作为眼内临床候选药物。这项研究旨在开发下一代小分子 PKM2 激活剂，专门用于眼内给药。所开发的化合物取代了 ML-265 的噻吩并吡嗪酮核心，并修饰了苯胺和甲基亚砜官能团。化合物 2 证明，从效力和疗效的角度来看，ML-265 支架的结构变化是可以承受的，可以与靶点以类似的模式结合，并能在视网膜外层应激模型中避免细胞凋亡。为了克服 ML-265 的低溶解度和功能基团问题，化合物 2 的核心结构具有高效和多功能性，可以加入多种功能基团，因此被用来开发新型 PKM2 激活剂，这种激活剂具有更好的溶解度，没有结构警示，并保留了药效。目前还没有其他分子可用于光感受器的代谢重编程。因此，这项研究首次培育了新一代新型、结构多样的小分子 PKM2 激活剂，并将其输送到眼睛中。
• Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer
  作者：Lei Wang、Kun Fang、Junfei Cheng、Yu Li、Yahui Huang、Shuqiang Chen、Guoqiang Dong、Shanchao Wu、Chunquan Sheng

  DOI：10.1021/acs.jmedchem.9b01626

  日期：2020.1.23

  Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.