4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]benzamide | 871483-20-4

• 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: 4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]benzamide
• CAS: 871483-20-4
• 化学式: C₁₉H₁₉ClN₂O₂
• 分子量: 342.825
• InChiKey: WQVMYRGATKLURS-UHFFFAOYSA-N

物化性质

• 沸点：
  589.6±50.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]benzamide 、 对溴溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以57%的产率得到N-(2-(1-(4-bromobenzyl)-5-methoxy-2-methyl-1H-indol-3-yl)ethyl)-4-chlorobenzamide
  参考文献：
  名称：

  Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors

  摘要：

  Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.073
• 作为产物：
  描述：

  2-(5-甲氧基-2-甲基-1H-吲哚-3-基)乙酰胺 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 63.0h， 生成 4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]benzamide
  参考文献：
  名称：

  Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors

  摘要：

  Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.073

文献信息

• 5,6 substituierte Benzamid-Derivate als Modulatoren des EP2-Rezeptors
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2149552A1

  公开（公告）日：2010-02-03

  Die vorliegende Erfindung betrifft 5,6 substituierte Benzamid-Derivate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie deren Verwendung zur Herstellung von pharmazeutischen Mitteln zur Behandlung von Erkrankungen und Indikationen, die im Zusammenhang stehen mit dem EP2 Rezeptor.

  本发明涉及通式（I）的 5,6-取代苯甲酰胺衍生物、其制备工艺及其在制备治疗与 EP2 受体有关的疾病和适应症的药物组合物中的用途。
• [DE] 5,6 SUBSTITUIERTE BENZAMID-DERIVATE ALS MODULATOREN DES EP2-REZEPTORS<br/>[EN] 5,6 SUBSTITUTED BENZAMIDE DERIVATIVES AS MODULATORS OF THE EP2 RECEPTOR<br/>[FR] DÉRIVÉS DE BENZAMIDES SUBSTITUÉS EN 5, 6 COMME MODULATEURS DU RÉCEPTEUR EP2
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2010012396A1

  公开（公告）日：2010-02-04

  Die vorliegende Erfindung betrifft 5,6 substituierte Benzamid-Derivate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie deren Verwendung zur Herstellung von pharmazeutischen Mitteln zur Behandlung von Erkrankungen und Indikationen, die im Zusammenhang stehen mit dem EP2-Rezeptor.