(R)-6-(6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)thieno[2,3-d]pyridazin-7(6H)-one | 868661-42-1

• 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: (R)-6-(6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)thieno[2,3-d]pyridazin-7(6H)-one
• 英文别名: 6-[6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyridin-3-yl]-2-[4-(trifluoromethyl)phenyl]thieno[2,3-d]pyridazin-7-one
• CAS: 868661-42-1
• 化学式: C₂₃H₂₀F₃N₅OS
• 分子量: 471.506
• InChiKey: VKAMBSPXFFZIQB-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  89.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-6-(6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)thieno[2,3-d]pyridazin-7(6H)-one 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 20.0h， 以17%的产率得到6-[5-bromo-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyridin-3-yl]-2-[4-(trifluoromethyl)phenyl]thieno[2,3-d]pyridazin-7-one
  参考文献：
  名称：

  [EN] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES AS MELANIN-CONCENTRATING HORMONE RECEPTOR AN TAGONISTS
  [FR] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES UTILISEES COMME ANTAGONISTES DU RECEPTEUR DE L'HORMONE CONCENTRANT LA MELANINE, ET COMPOSITIONS ET PROCEDES ASSOCIES

  摘要：

  黑色素浓缩激素（MCH）受体拮抗剂被披露具有治疗基于MCH受体的疾病如肥胖的效用。本发明的化合物具有以下结构：包括立体异构体、前药和其药用盐，其中R1、R2、R5、Het、X和Cyc如本文所定义。还披露了含有本发明化合物的组合物，以及与其使用相关的方法。

  公开号：

  WO2005103039A1
• 作为产物：
  描述：

  4-chloro-2-(tetrahydropyran-2-yl)-5-(4-trifluoromethylphenylethynyl)-2H-pyridazin-3-one 在 盐酸 、 sodium sulfide 、 copper(l) iodide 、 (1S,2S)-(+)-1,2-环己二胺 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 (R)-6-(6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)thieno[2,3-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  A Thienopyridazinone-Based Melanin-Concentrating Hormone Receptor 1 Antagonist with Potent in Vivo Anorectic Properties

  摘要：

  Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg(-1).

  DOI：

  10.1021/jm051263c

文献信息

• A Thienopyridazinone-Based Melanin-Concentrating Hormone Receptor 1 Antagonist with Potent in Vivo Anorectic Properties
  作者：Brian Dyck、Stacy Markison、Liren Zhao、Junko Tamiya、Jonathan Grey、Martin W. Rowbottom、Mingzhu Zhang、Troy Vickers、Katie Sorensen、Christi Norton、Jenny Wen、Christopher E. Heise、John Saunders、Paul Conlon、Ajay Madan、David Schwarz、Val S. Goodfellow

  DOI：10.1021/jm051263c

  日期：2006.6.1

  Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg(-1).
• [EN] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES AS MELANIN-CONCENTRATING HORMONE RECEPTOR AN TAGONISTS<br/>[FR] 2- (3-AMINOPYRROLIDIN-1-YL) PYRIDINES UTILISEES COMME ANTAGONISTES DU RECEPTEUR DE L'HORMONE CONCENTRANT LA MELANINE, ET COMPOSITIONS ET PROCEDES ASSOCIES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005103039A1

  公开（公告）日：2005-11-03

  Melanin-concentrating hormone (MCH) receptor antagonists are disclosed having utility for the treatment of MCH receptor-based disorders such as obesity. The compounds of this invention have the following structure: including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein R1, R2, R5, Het, X and Cyc are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.

  黑色素浓缩激素（MCH）受体拮抗剂被披露具有治疗基于MCH受体的疾病如肥胖的效用。本发明的化合物具有以下结构：包括立体异构体、前药和其药用盐，其中R1、R2、R5、Het、X和Cyc如本文所定义。还披露了含有本发明化合物的组合物，以及与其使用相关的方法。