1-[6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-indol-1-yl]-ethanone | 461658-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-indol-1-yl]-ethanone
• 英文别名: cis-1-Acetyl-6-(3,5-dimethylpiperazin-1-yl)-5-methoxyindoline；1-[6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-5-methoxy-2,3-dihydroindol-1-yl]ethanone
• CAS: 461658-31-1
• 化学式: C₁₇H₂₅N₃O₂
• 分子量: 303.404
• InChiKey: LDQZWVSSIRADGL-TXEJJXNPSA-N

物化性质

• 沸点：
  551.0±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-indol-1-yl]-ethanone 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 [6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-indol-1-yl]-(2'-methyl-4'-pyrimidin-2-yl-biphenyl-4-yl)-methanone
  参考文献：
  名称：

  Identification of a potent and selective 5-HT1B receptor antagonist

  摘要：

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.085
• 作为产物：
  描述：

  N-乙酰基吲哚啉 在 过氧乙酸 、 palladium diacetate 、 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 三氯化铝 、 potassium carbonate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 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， 生成 1-[6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-indol-1-yl]-ethanone
  参考文献：
  名称：

  Identification of a potent and selective 5-HT1B receptor antagonist

  摘要：

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.085

文献信息

• Piperazine derivatives their preparation and uses in therapy
  申请人：——

  公开号：US20040142925A1

  公开（公告）日：2004-07-22

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof are disclosed: 1 in which R a is a group of formula (i) 2 wherein P 2 is phenyl, naphthyl, heteroaryl or a 5 to 7 membered heterocyclic ring; P 3 is phenyl, naphthyl or heteroaryl; R 1 is NR 4 COR 5 , NR 4 SO 2 R 5 , CH 2 NR 4 SO 2 R 5 , CH 2 NR 4 COR 5 or CH 2 NR 4 CO 2 R 5 where R 4 and R 5 are independently hydrogen or C 1-6 alkyl; R 2 and R 3 are independently halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, COC 1-6 alkyl, haloC 1-6 alkyl, cyano or NR 6 R 7 where R 6 and R 7 are independently hydrogen or C 1-6 alkyl; b and c are independently 0, 1, 2 or 3; Y is a single bond, CH 2 or NH; W is —(CR 9 R 10 ) t - where t is 2, 3 or 4 and R 9 and R 10 are independently hydrogen or C 1-6 alkyl or W is a group CH═CH; R b is hydrogen, halogen, C 1-6 alkyl, haloC 1-6 alkyl, COC 1-6 alkyl, cyano or C 1-6 alkoxy; and R c is hydrogen or C 1-6 alkyl. Processes for preparation of the compounds and their uses in therapy, particularly depression, are also disclosed.

  揭示了式（I）的化合物或其药学上可接受的盐：其中，R是式（i）的基团，式中P2是苯基、萘基、杂环芳基或5至7成员杂环环；P3是苯基、萘基或杂环芳基；R1是NR4COR5、NR4SO2R5、CH2NR4SO2R5、CH2NR4COR5或CH2NR4CO2R5，其中R4和R5独立地为氢或C1-6烷基；R2和R3独立地为卤素、C1-6烷基、C3-6环烷基、C1-6烷氧基、COC1-6烷基、卤基C1-6烷基、氰基或NR6R7，其中R6和R7独立地为氢或C1-6烷基；b和c独立地为0、1、2或3；Y为单键、CH2或NH；W为—（CR9R10）t-，其中t为2、3或4，且R9和R10独立地为氢或C1-6烷基，或W为基团CH═CH；Rb为氢、卤素、C1-6烷基、卤基C1-6烷基、COC1-6烷基、氰基或C1-6烷氧基；Rc为氢或C1-6烷基。还揭示了制备这些化合物的方法以及它们在治疗中的用途，特别是抑郁症。
• Piperazine derivatives, their preparation and uses in therapy
  申请人：SmithKline Beecham plc

  公开号：US07109201B2

  公开（公告）日：2006-09-19

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof are disclosed: in which Ra is a group of formula (i) wherein P2 is phenyl, naphthyl, heteroaryl or a 5 to 7 membered heterocyclic ring; P3 is phenyl, naphthyl or heteroaryl; R1 is NR4COR5, NR4SO2R5, CH2NR4SO2R5, CH2NR4COR5 or CH2NR4CO2R5 where R4 and R5 are independently hydrogen or C1-6alkyl; R2 and R3 are independently halogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy, COC1-6alkyl, haloC1-6alkyl, cyano or NR6R7 where R6 and R7 are independently hydrogen or C1-6alkyl; b and c are independently 0, 1, 2 or 3; Y is a single bond, CH2 or NH; W is —(CR9R10)t—where t is 2, 3 or 4 and R9 and R10 are independently hydrogen or C1-6alkyl or W is a group CH═CH; Rb is hydrogen, halogen, C1-6alkyl, haloC1-6alkyl, COC1-6alkyl, cyano or C1-6alkoxy; and Rc is hydrogen or C1-6alkyl. Processes for preparation of the compounds and their uses in therapy, particularly depression, are also disclosed.

  公开了式（I）的化合物或其药学上可接受的盐：其中Ra是式（i）的基团，其中P2是苯基，萘基，杂环芳基或5到7成员杂环环；P3是苯基，萘基或杂环芳基；R1是NR4COR5，NR4SO2R5，CH2NR4SO2R5，CH2NR4COR5或CH2NR4CO2R5，其中R4和R5独立地是氢或C1-6烷基；R2和R3独立地是卤素，C1-6烷基，C3-6环烷基，C1-6烷氧基，COC1-6烷基，卤基C1-6烷基，氰基或NR6R7，其中R6和R7独立地是氢或C1-6烷基；b和c独立地为0、1、2或3；Y是单键，CH2或NH；W是—（CR9R10）t—，其中t为2、3或4，R9和R10独立地是氢或C1-6烷基，或W是基团CH═CH；Rb是氢，卤素，C1-6烷基，卤基C1-6烷基，COC1-6烷基，氰基或C1-6烷氧基；Rc是氢或C1-6烷基。还公开了制备这些化合物的方法以及它们在治疗中的用途，特别是抑郁症。
• PIPERAZINE DERIVATIVES AND THEIR USE AS 5-HT1B LIGANDS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1368337B1

  公开（公告）日：2005-06-15
• US7109201B2
  申请人：——

  公开号：US7109201B2

  公开（公告）日：2006-09-19
• Identification of a potent and selective 5-HT1B receptor antagonist
  作者：Paul A. Wyman、Howard R. Marshall、Sean T. Flynn、Ron J. King、Mervyn Thompson、Paul W. Smith、Michael S. Hadley、Gary W. Price、Claire M. Scott、Lee A. Dawson

  DOI：10.1016/j.bmcl.2005.07.085

  日期：2005.11

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.