4-bromo-2-(3,4-dichlorophenyl)-2-methylbutyric acid methyl ester | 1093078-84-2

• 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: 4-bromo-2-(3,4-dichlorophenyl)-2-methylbutyric acid methyl ester
• 英文别名: 4-bromo-2-(3,4-dichloro-phenyl)-2-methyl-butyric acid methyl ester；methyl 4-bromo-2-(3,4-dichlorophenyl)-2-methylbutanoate
• CAS: 1093078-84-2
• 化学式: C₁₂H₁₃BrCl₂O₂
• 分子量: 340.044
• InChiKey: RGJAAYLPVHWMBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-甲基-N-(4-哌啶基)乙酰胺 、 4-bromo-2-(3,4-dichlorophenyl)-2-methylbutyric acid methyl ester 以 N,N-二甲基乙酰胺 为溶剂， 反应 86.0h， 以95%的产率得到4-[4-(acetyl(methylamino))piperidin-1-yl]-2-(3,4-dichlorophenyl)-2-methylbutyric acid methyl ester
  参考文献：
  名称：

  Identification of a Critical Residue in the Transmembrane Domain 2 of Tachykinin Neurokinin 3 Receptor Affecting the Dissociation Kinetics and Antagonism Mode of Osanetant (SR 142801) and Piperidine-Based Structures

  摘要：

  In this study, we show that compound 3 (osanetant) binds with a pseudoirreversible, apparent noncompetitive mode of antagonism at the guinea pig NK(3), while it behaves competitively at the human NK(3). This difference is caused by a slower dissociation rate of compound 3 at the guinea pig NK(3) compared to human NK(3). The only amino acid difference between the human and guinea pig NK(3) in the binding site (Thr 139(2.58) in human, corresponding to Ala 114(2.58) in guinea pig) has been shown to be responsible for the different behavior. Compound 1 (talnetant), however, behaves competitively at both receptors. Using these data, 3D homology modeling, and site-directed mutagenesis, a model has been developed to predict the mode of antagonism of NK(3) antagonists based on their binding mode. This model was successfully used to predict the mode of antagonism of compounds of another chemical series including piperidine-based structures at human and guinea pig NK(3).

  DOI：

  10.1021/jm900948q
• 作为产物：
  描述：

  甲醇 、 以 甲苯 为溶剂， 反应 16.0h， 生成 4-bromo-2-(3,4-dichlorophenyl)-2-methylbutyric acid methyl ester
  参考文献：
  名称：

  PIPERAZINE AND [1,4]DIAZEPAN DERIVATIVES AS NK ANTAGONISTS

  摘要：

  本发明涉及一种具有如下式I的化合物，其中R1、R2、R3、R4、R9、R10、m和n如本文所定义，或其药学上可接受的酸盐。本化合物是高潜力的NK-3受体拮抗剂，用于治疗抑郁症、双相情感障碍、疼痛、精神病、帕金森病、精神分裂症、焦虑症和注意缺陷多动障碍（ADHD）。

  公开号：

  US20080312216A1

文献信息

• PIPERIDINE DERIVATIVES AS NK3 ANTAGONISTS
  申请人：Knust Henner

  公开号：US20090076081A1

  公开（公告）日：2009-03-19

  The invention relates to a compound of formula wherein Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , R 5 , and R 5′ or to a pharmaceutically active salt thereof. The 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).

  该发明涉及一种化合物，其化学式为Ar1、Ar2、R1、R2、R3、R4、R5和R5′，或其药用活性盐。这些化合物是用于治疗抑郁症、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）的高潜力NK-3受体拮抗剂。
• Piperazine and [1,4]diazepan derivatives as NK antagonists
  申请人：Hoffmann-La Roche Inc.

  公开号：US07592345B2

  公开（公告）日：2009-09-22

  The present invention relates to a compound of formula I wherein R1, R2, R3, R4, R9, R10, m and n are as defined herein, or to a pharmaceutically acceptable acid addition salt thereof. The present compounds are high potential NK-3 receptor antagonists for the treatment of depression, bipolar disorders, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

  本发明涉及公式I的化合物，其中R1、R2、R3、R4、R9、R10、m和n如本文所定义，或其药学上可接受的酸加盐。本化合物是高潜力的NK-3受体拮抗剂，可用于治疗抑郁症、双相情感障碍、疼痛、精神病、帕金森病、精神分裂症、焦虑症和注意力缺陷多动障碍（ADHD）。
• PIPERAZINE AND Ý1,4¨DIAZEPAN DERIVATIVES AS NK ANTAGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2167509A1

  公开（公告）日：2010-03-31
• PIPERIDINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2200982B1

  公开（公告）日：2012-03-14
• US7592345B2
  申请人：——

  公开号：US7592345B2

  公开（公告）日：2009-09-22