ethyl 1-(4-chlorophenyl)-3-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenylcarbamoyl)-1H-pyrazole-4-carboxylate | 1224172-16-0

• 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: ethyl 1-(4-chlorophenyl)-3-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenylcarbamoyl)-1H-pyrazole-4-carboxylate
• 英文别名: Ethyl 1-(4-chlorophenyl)-3-[[3-methoxy-4-(2-trimethylsilylethoxymethoxy)phenyl]carbamoyl]pyrazole-4-carboxylate
• CAS: 1224172-16-0
• 化学式: C₂₆H₃₂ClN₃O₆Si
• 分子量: 546.095
• InChiKey: XRDZLZSLWTUVOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-chlorophenyl)-3-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenylcarbamoyl)-1H-pyrazole-4-carboxylate 在 锂硼氢 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 2-(4-chlorophenyl)-5-(4-hydroxy-3-methoxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one
  参考文献：
  名称：

  Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup

  摘要：

  Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.008
• 作为产物：
  描述：

  3-benzyl 4-ethyl 1-(4-chlorophenyl)-1H-pyrazole-3,4-dicarboxylate 在 palladium 10% on activated carbon 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 9.5h， 生成 ethyl 1-(4-chlorophenyl)-3-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenylcarbamoyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup

  摘要：

  Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.008

文献信息

• [EN] AZOLOPYRROLONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR-1 DE L'HORMONE DE MÉLANO-CONCENTRATION D'AZOLOPYRROLONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010047956A9

  公开（公告）日：2011-10-06