tert-butyl 1-(5-(1-(4-chlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxamido)pyridin-2-yl)pyrrolidin-3-yl(methyl)carbamate | 1224172-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 1-(5-(1-(4-chlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxamido)pyridin-2-yl)pyrrolidin-3-yl(methyl)carbamate
• 英文别名: tert-butyl N-[1-[5-[[1-(4-chlorophenyl)-4-(hydroxymethyl)pyrazole-3-carbonyl]amino]pyridin-2-yl]pyrrolidin-3-yl]-N-methylcarbamate
• CAS: 1224172-22-8
• 化学式: C₂₆H₃₁ClN₆O₄
• 分子量: 527.023
• InChiKey: ZQEYNFVYZBRQIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(5-(1-(4-chlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxamido)pyridin-2-yl)pyrrolidin-3-yl(methyl)carbamate 在 盐酸 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-(4-chlorophenyl)-5-(6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)-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：

  ethyl 1-(4-chlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 18.0h， 生成 tert-butyl 1-(5-(1-(4-chlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxamido)pyridin-2-yl)pyrrolidin-3-yl(methyl)carbamate
  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