1-(benzo[d]thiazol-2-yl)-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-3-(p-tolyl)-1H-pyrazole-4-carboxamide | 1609564-70-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(benzo[d]thiazol-2-yl)-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-3-(p-tolyl)-1H-pyrazole-4-carboxamide
• 英文别名: 1-(1,3-benzothiazol-2-yl)-N-(4-methyl-3-morpholin-4-ylsulfonylphenyl)-3-(4-methylphenyl)pyrazole-4-carboxamide
• CAS: 1609564-70-6
• 化学式: C₂₉H₂₇N₅O₄S₂
• 分子量: 573.696
• InChiKey: CPCPPWITBIJZTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (E)-2-(2-(1-(p-tolyl)ethylidene)hydrazinyl)benzo[d]thiazole 在 Jones reagent 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氯氧磷 作用下， 以 氘代氯仿 、 二氯甲烷 、 丙酮 为溶剂， 反应 31.0h， 生成 1-(benzo[d]thiazol-2-yl)-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-3-(p-tolyl)-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Identification of trisubstituted-pyrazol carboxamide analogs as novel and potent antagonists of farnesoid X receptor

  摘要：

  Farnesoid X receptor (FXR, NRIH4) plays a major role in the control of cholesterol metabolism. This suggests that antagonizing the transcriptional activity of FXR is a potential means to treat cholestasis and related metabolic disorders. Here we describe the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of trisubstituted-pyrazol carboxamides as novel and potent FXR antagonists. One of these novel FXR antagonists, 4j has an IC50 of 7.5 nM in an FXR binding assay and 468.5 nM in a cell-based FXR antagonistic assay. Compound 4j has no detectable FXR agonistic activity or cytotoxicity. Notably, 4j is the most potent FXR antagonist identified to date; it has a promising in vitro profile and could serve as an excellent chemical tool to elucidate the biological function of FXR. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.014

文献信息

• Farnesoid X receptor antagonists
  申请人：City of Hope

  公开号：US10611729B2

  公开（公告）日：2020-04-07

  Provided herein are Famesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.

  本文提供了具有式(I)结构的类雌激素X受体(FXR)拮抗剂，以及包含式(I)化合物和药学上可接受的赋形剂的药物组合物。还提供了拮抗 FXR 的方法，以及治疗有需要的受试者的代谢疾病的方法，包括向受试者施用有效量的式 (I) 的 FXR 拮抗剂。
• [EN] FARNESOID X RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR X DE FARNÉSOÏDE
  申请人：HOPE CITY

  公开号：WO2015116856A3

  公开（公告）日：2015-11-05
• FARNESOID X RECEPTOR ANTAGONISTS
  申请人：City of Hope

  公开号：US20170008851A1

  公开（公告）日：2017-01-12

  Provided herein are Farnesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.
• US9944605B2
  申请人：——

  公开号：US9944605B2

  公开（公告）日：2018-04-17
• Identification of trisubstituted-pyrazol carboxamide analogs as novel and potent antagonists of farnesoid X receptor
  作者：Donna D. Yu、Wenwei Lin、Barry M. Forman、Taosheng Chen

  DOI：10.1016/j.bmc.2014.04.014

  日期：2014.6

  Farnesoid X receptor (FXR, NRIH4) plays a major role in the control of cholesterol metabolism. This suggests that antagonizing the transcriptional activity of FXR is a potential means to treat cholestasis and related metabolic disorders. Here we describe the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of trisubstituted-pyrazol carboxamides as novel and potent FXR antagonists. One of these novel FXR antagonists, 4j has an IC50 of 7.5 nM in an FXR binding assay and 468.5 nM in a cell-based FXR antagonistic assay. Compound 4j has no detectable FXR agonistic activity or cytotoxicity. Notably, 4j is the most potent FXR antagonist identified to date; it has a promising in vitro profile and could serve as an excellent chemical tool to elucidate the biological function of FXR. (C) 2014 Elsevier Ltd. All rights reserved.