2-(4-chlorophenyl)-5-(4-(2-hydroxypropoxy)-3-methoxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one | 1224170-91-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-chlorophenyl)-5-(4-(2-hydroxypropoxy)-3-methoxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one
• 英文别名: 2-(4-chlorophenyl)-5-[4-(2-hydroxypropoxy)-3-methoxyphenyl]-4H-pyrrolo[3,4-c]pyrazol-6-one
• CAS: 1224170-91-5
• 化学式: C₂₁H₂₀ClN₃O₄
• 分子量: 413.861
• InChiKey: KPVLBXKYXNCENI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  76.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-4-(hydroxymethyl)-N-(3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)phenyl)-1H-pyrazole-3-carboxamide 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 2-(4-chlorophenyl)-5-(4-(2-hydroxypropoxy)-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

文献信息

• AZOLOPYRROLONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
  申请人：Devasthale Pratik

  公开号：US20110195934A1

  公开（公告）日：2011-08-11

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable faints thereof according to wherein all of the variables are defined herein.

  本申请提供了化合物，包括所有立体异构体、溶剂化物、前药和药学上可接受的盐，其中所有变量在此定义。
• [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
• US8415386B2
  申请人：——

  公开号：US8415386B2

  公开（公告）日：2013-04-09
• Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup
  作者：Pratik Devasthale、Wei Wang、Andres S. Hernandez、Fang Moore、Kishore Renduchintala、Radhakrishnan Sridhar、Mary Ann Pelleymounter、Daniel Longhi、Ning Huang、Neil Flynn、Anthony V. Azzara、Kenneth Rohrbach、James Devenny、Suzanne Rooney、Michael Thomas、Susan Glick、Helen Godonis、Susan Harvey、Mary Jane Cullen、Hongwei Zhang、Christian Caporuscio、Paul Stetsko、Mary Grubb、Christine Huang、Lisa Zhang、Chris Freeden、Yi-Xin Li、Brian J. Murphy、Jeffrey A. Robl、William N. Washburn

  DOI：10.1016/j.bmcl.2015.05.008

  日期：2015.7

  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.