2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl methanesulfonate | 910457-38-4

• 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: 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl methanesulfonate
• 英文别名: 2-[1-(4-Chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]ethyl methanesulfonate
• CAS: 910457-38-4
• 化学式: C₂₀H₂₀ClNO₅S
• 分子量: 421.901
• InChiKey: LYPADUOVGJRNAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl methanesulfonate 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 3-(2-azidoethyl)-5-methoxy-2-methylindolyl 4-chlorophenyl ketone
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Indomethacin Derivatives as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors

  摘要：

  Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.

  DOI：

  10.1021/jm0611861
• 作为产物：
  描述：

  吲哚美辛 在 dimethyl sulfide borane 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl methanesulfonate
  参考文献：
  名称：

  使用双哌啶二氧化硫（一种未充分利用的 SO2 转移试剂）光氧化还原催化制备砜

  摘要：

  据报道，由硅烷介导的卤素原子转移活化的烷基溴制备光氧化还原催化的一锅砜。在此过程中，人们发现之前未利用的 SO 2加合物双（哌啶）二氧化硫（PIPSO）是反应条件下自由基捕获的最佳 SO 2来源。制备了烷基和芳基砜以及磺酰化 API。

  DOI：

  10.1002/chem.202303976

文献信息

• Photoinduced <scp>NaI‐Promoted</scp> Radical Borylation of Alkyl Halides and Pseudohalides
  作者：Chenglan Wang、Lu Zhou、Kai Yang、Feng Zhang、Qiuling Song

  DOI：10.1002/cjoc.202100115

  日期：2021.7

  A method for photoinduced NaI-promoted radical borylation of aliphatic halides and pseudohalides with bis(catecholato)diboron (B2cat2) as the boron source is introduced. The borylation reaction is operationally simple and shows high functional group tolerance and broad substrate scope. Preliminary mechanistic studies suggest that the reaction proceeds through SN2-based radical-generation strategy.

  介绍了一种以双(儿茶酚)二硼(B 2 cat 2 )为硼源的光诱导NaI促进的脂肪族卤化物和拟卤化物自由基硼化的方法。硼酸化反应操作简单，显示出高官能团耐受性和广泛的底物范围。初步机理研究表明，该反应通过基于S N 2 的自由基生成策略进行。
• WO2006/99416
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] 2-METHYL INDOLE CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE<br/>[FR] INHIBITEURS SELECTIFS DE LA 2-METHYLE-INDOLE CYCLOOXYGENASE-2, COMPOSITIONS ET PROCEDES D'UTILISATION
  申请人：NITROMED INC

  公开号：WO2006099416A1

  公开（公告）日：2006-09-21

  [EN] The invention describes compositions and kits comprising 2-methyl indole cyclooxygenase 2 (COX-2) selective inhibitors or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The 2-methyl indole cyclooxygenase 2 selective inhibitors can be optionally substituted with at least one nitric oxide enhancing group. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders and/or improving the gastrointestinal properties of COX-2 selective inhibitors; (c) facilitating wound healing; (d) treating renal and/or respiratory toxicities; (e) treating disorders resulting from elevated levels of cyclooxygenase-2; (f) improving the cardiovascular profile of COX-2 selective inhibitors; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; (j) treating diseases caused by endothelial dysfunctions; (k) treating inflammatory disease states and/or disorders; (1) treating ophthalmic disorders; and (m) treating peripheral vascular diseases. The nitric oxide enhancing groups are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
  [FR] L'invention décrit des compositions et des kits comprenant des inhibiteurs 2-méthyle-indole sélectifs de la cyclooxygénase 2 (COX-2) ou des sels desdits inhibiteurs acceptables sur le plan pharmaceutique et, éventuellement au moins un composé renforçateur monoxyde d'azote et/ou au moins un agent thérapeutique. Les inhibiteurs 2-méthyle-indole sélectifs de la cyclooxygénase 2 peuvent éventuellement être substitués avec au moins un groupe renforçateur ***monoxyde d'azote. L'invention prévoit également des procédés destinés à (a) traiter l'inflammation, la douleur et la fièvre ; (b) traiter les troubles gastro-intestinaux et/ou améliorer les propriétés gastro-intestinales d'inhibiteurs sélectifs de COX-2 ; (c) faciliter la guérison des blessures ; (d) traiter les intoxications rénales et/ou respiratoires ; (e) traiter des troubles résultant de niveaux élevés de cyclooxygénase-2 ; (f) améliorer le profil cardiovasculaire des inhibiteurs sélectifs de COX-2 ; (g) traiter des maladies résultant de stress oxydatif ; (h) traiter les dysfontionnements endothéliaux ; (j) traiter des maladies dues aux dysfonctionnement endothéliaux ; (k) traiter des états et/ou des troubles dus à une maladie inflammatoire ; (l) traiter des troubles ophthalmiques ; et (m) traiter des maladies vasculaires périphériques. Les groupes renforçateurs monoxyde d'azote sont des nitrates organiques, des nitrites organiques, des nitrosothiols, des thionitrites, des thionitrates, des NONOates, des donneurs hétérocycliques d'acide nitrique et/ou des nitroxydes. Les donneurs de monoxyde d'azote hétérocycliques sont des furoxanes, des sydnonimines, des oxatriazole-5-ones et/ou des oxatriazole-5-imines.
• Structure-Based Design, Synthesis, and Biological Evaluation of Indomethacin Derivatives as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors
  作者：Shiow-Jyi Wey、Michael E. Augustyniak、Edward D. Cochran、James L. Ellis、Xinqin Fang、David S. Garvey、David R. Janero、L. Gordon Letts、Allison M. Martino、Terry L. Melim、Madhavi G. Murty、Steward K. Richardson、Joseph D. Schroeder、William M. Selig、A. Mark Trocha、Roseanne S. Wexler、Delano V. Young、Irina S. Zemtseva、Brian M. Zifcak

  DOI：10.1021/jm0611861

  日期：2007.12.13

  Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.
• Photoredox‐Catalyzed Preparation of Sulfones Using <i>Bis</i>‐Piperidine Sulfur Dioxide – An Underutilized Reagent for SO₂ Transfer
  作者：Oliver M. Griffiths、Henrique A. Esteves、Darcy C. Emmet、Steven V. Ley

  DOI：10.1002/chem.202303976

  日期：2024.2.26

  photoredox-catalyzed one-pot sulfone preparation is reported from alkyl bromides activated by silane-mediated halogen atom transfer. In the process, a previously unutilized SO2 adduct bis(piperidine) sulfur dioxide – or PIPSO – was found to be the best source of SO2 for radical capture under the reaction conditions. Alkyl and aryl sulfones were prepared as well as sulfonylated APIs.

  据报道，由硅烷介导的卤素原子转移活化的烷基溴制备光氧化还原催化的一锅砜。在此过程中，人们发现之前未利用的 SO 2加合物双（哌啶）二氧化硫（PIPSO）是反应条件下自由基捕获的最佳 SO 2来源。制备了烷基和芳基砜以及磺酰化 API。