[(3R,4S)-3-[(R)-1-(5-Chloro-pyridin-2-yloxy)-2-hydroxy-ethyl]-4-(3,4-difluoro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone | 1115961-51-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [(3R,4S)-3-[(R)-1-(5-Chloro-pyridin-2-yloxy)-2-hydroxy-ethyl]-4-(3,4-difluoro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone
• 英文别名: [(3R,4S)-3-[(R)-1-(5-chloropyridin-2-yloxy)-2-hydroxyethyl]-4-(3,4-difluorophenyl)pyrrolidin-1-yl]-(2-methylpyrimidin-5-yl)-methanone；[(3R,4S)-3-[(1R)-1-(5-chloropyridin-2-yl)oxy-2-hydroxyethyl]-4-(3,4-difluorophenyl)pyrrolidin-1-yl]-(6-methylpyridazin-4-yl)methanone
• CAS: 1115961-51-7
• 化学式: C₂₃H₂₁ClF₂N₄O₃
• 分子量: 474.895
• InChiKey: XWLXWCSCHTXBKC-LQWHRVPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  88.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [(3R,4S)-3-[(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-difluoro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以84%的产率得到[(3R,4S)-3-[(R)-1-(5-Chloro-pyridin-2-yloxy)-2-hydroxy-ethyl]-4-(3,4-difluoro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone
  参考文献：
  名称：

  PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS

  摘要：

  该发明涉及一种化合物，其化学式为I，其中Ar1、Ar2、R1、R2、R3、R4、n、o、p和q如本文所定义，并且涉及其药用活性盐，包括化合物(I)的所有立体异构形式、单个对映体异构体和对映体，以及其外消旋和非外消旋混合物。这些化合物是高潜力的NK-3受体拮抗剂，用于治疗抑郁症、疼痛、精神病、帕金森病、精神分裂症、焦虑和注意力缺陷多动障碍（ADHD）。

  公开号：

  US20090042896A1

文献信息

• SUBSTITUTED BICYCLOLACTAM COMPOUNDS
  申请人：Pfizer Products Inc.

  公开号：EP2185567A2

  公开（公告）日：2010-05-19
• US8012998B2
  申请人：——

  公开号：US8012998B2

  公开（公告）日：2011-09-06
• [EN] SUBSTITUTED BICYCLOLACTAM COMPOUNDS<br/>[FR] BICYCLOLACTAMES SUBSTITUÉS
  申请人：PFIZER PROD INC

  公开号：WO2009016462A2

  公开（公告）日：2009-02-05

  The invention provides compounds of formula (1), and the pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5a, R5b, R5c, R5d, Q, A, Z, and R7 are as described herein; compositions thereof; and uses thereof for the treatment of diabetes and obesity.
• [EN] PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS DE PYRROLIDINE ARYLE-ÉTHER UTILISÉS COMME ANTAGONISTES DES RÉCEPTEURS NK3
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009019163A1

  公开（公告）日：2009-02-12

  The invention relates to a compound of general formula (I) wherein Ar1 is aryl or a five or six membered heteroaryl; Ar2 is aryl or a five or six membered heteroaryl; R1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, S-lower alkyl, -S(O)2-lower alkyl, -S(O)2-di-lower alkyl amino, -(CH2)qR, cyano, amino, mono or di-lower alkyl amino, NHC(O)-lower alkyl, cycloalkyl or is or a five membered heteroaryl, optionally substituted by lower alkyl; wherein R is cyano, di-lower alkyl amino or pyrrolidin-1-yl; R2 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen or cyano; R3 is hydrogen or lower alkyl or CH2OH; R4 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen or cyano; n is 1, 2 or 3; in case n is 2 or 3, R1 may be the same or different; o is 1, 2 or 3; in case o is 2 or 3, R2 may be the same or different; p is 1, 2 or 3; in case p is 2 or 3, R4 may be the same or different; q is 1 or 2; or to a pharmaceutically active salt thereof, including all stereoisomeric forms, individual diastereoisomers and enantiomers of the compound of formula (I) as well as racemic and non-racemic mixtures thereof. It has been found that the present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).