[(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-hydroxymethyl-pyrrolidin-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone

• 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: [(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-hydroxymethyl-pyrrolidin-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone
• 英文别名: [(3R,4S)-3-(3,4-dichlorophenyl)-4-(hydroxymethyl)pyrrolidin-1-yl]-(4-methylsulfonylpiperazin-1-yl)methanone
• 化学式: C₁₇H₂₃Cl₂N₃O₄S
• 分子量: 436.359
• InChiKey: HTXSEHJHAASEMQ-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  89.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-hydroxymethyl-pyrrolidin-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone 、 对氯苯酚 在 三苯基膦树脂 、 偶氮二甲酸二叔丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成 [(3SR,4RS)-3-(4-chloro-phenoxymethyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone
  参考文献：
  名称：

  PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS

  摘要：

  该发明涉及一种通式为的化合物，其中Ar、R1、R2、R3、R4、n、o、p、s、X和如本文所定义的或其药用活性盐，包括通式（I）化合物的所有立体异构形式、各个对映异构体和对映体，以及它们的消旋和非消旋混合物。这些化合物是治疗抑郁症、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。

  公开号：

  US20090054644A1
• 作为产物：
  描述：

  (3SR,4RS)-4-(3,4-dichloro-phenyl)-1-(4-methanesulfonyl-piperazine-1-carbonyl)-pyrrolidine-3-carboxylic acid ethyl ester 在 锂硼氢 、 水 作用下， 以 甲醇 为溶剂， 反应 50.0h， 以81%的产率得到[(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-hydroxymethyl-pyrrolidin-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone
  参考文献：
  名称：

  PYRROLIDINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS

  摘要：

  本发明涉及公式I的化合物，其中A、Ar、R、R2、R3、R4、p和o如规范和声明中定义的那样，或其药用活性盐。该化合物是高潜力的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、躁郁症、焦虑症和注意力缺陷多动障碍（ADHD）。

  公开号：

  US20100210659A1

文献信息

• US7812021B2
  申请人：——

  公开号：US7812021B2

  公开（公告）日：2010-10-12
• [EN] PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS<br/>[FR] PYRROLIDINE ARYL-ÉTHER EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DE NK3
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009024502A1

  公开（公告）日：2009-02-26

  The invention relates to a compound of general formula (I) wherein is aryl or a five or six membered heteroaryl; is a six to nine membered mono or bi-heterocyclic group, wherein X may be a carbon atom, SO2 or a further hetero atom, selected from the group consisting of N or O; if X is a carbon atom, O, SO2 or unsubstituted N, then R1 is hydrogen, hydroxy, cyano, -(CH 2 ) q -OH, -(CH 2 ) q -NRR', -(CH 2 )q-CN, lower alkyl, -S(O) 2 -lower alkyl, -NR-S(O) 2 -lower alkyl, -C(O)-lower alkyl, -NR-C(O)-lower alkyl, phenyl, or is a heterocyclic group selected from piperidinyl-2-one; if X is a N-atom, substituted by R 1, then R 1 is hydrogen, -(CH 2 ) q -OH, -(CH 2 ) q -NRR', -(CH 2 )q-CN, lower alkyl, -S(O) 2 - lower alkyl, aryl or a five or six membered heteroaryl or -C(O)-lower alkyl, provided that q is 2 or 3. R/R' are independently from each other hydrogen or lower alkyl; R 2 is hydrogen, halogen, lower alkyl, cyano, lower alkoxy substituted by halogen, lower alkyl substituted by halogen or is a five or six membered heteroaryl; R 3 is hydrogen or halogen; R 4 is hydrogen or lower alkyl; n is 1 or 2; in case n is 2, R 1 may be the same or different; o is 1 or 2; in case o is 2, R 2 may be the same or different; p is 1 or 2; in case p is 2, R 3 may be the same or different; q is 1, 2 or 3; s is 0, 1, 2, 3 or 4; 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).
• PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS
  申请人：Jablonski Philippe

  公开号：US20090054644A1

  公开（公告）日：2009-02-26

  The invention relates to a compound of general formula wherein Ar, R 1 , R 2 , R 3 , R 4 , n, o, p, s, X and are as defined herein 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. 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).

  该发明涉及一种通式为的化合物，其中Ar、R1、R2、R3、R4、n、o、p、s、X和如本文所定义的或其药用活性盐，包括通式（I）化合物的所有立体异构形式、各个对映异构体和对映体，以及它们的消旋和非消旋混合物。这些化合物是治疗抑郁症、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。
• PYRROLIDINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS
  申请人：Knust Henner

  公开号：US20100210659A1

  公开（公告）日：2010-08-19

  The present invention relates to a compounds of formula I wherein A, Ar, R, R2, R3, R4, p, and o are as defined in the specification and claims or to a pharmaceutically active salt thereof. The present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, bipolar disorders, anxiety and attention deficit hyperactivity disorder (ADHD).

  本发明涉及公式I的化合物，其中A、Ar、R、R2、R3、R4、p和o如规范和声明中定义的那样，或其药用活性盐。该化合物是高潜力的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、躁郁症、焦虑症和注意力缺陷多动障碍（ADHD）。