6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-1H-indole | 332399-04-9

• 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: 6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-1H-indole
• 英文别名: cis-6-(3,5-Dimethylpiperazin-1-yl)-5-methoxyindoline；6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-5-methoxy-2,3-dihydro-1H-indole
• CAS: 332399-04-9
• 化学式: C₁₅H₂₃N₃O
• 分子量: 261.367
• InChiKey: YUGOSHZSZJPSHD-PHIMTYICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  36.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-1H-indole 、 2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid 在 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 SB-616234-A
  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 盐酸 、 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 6-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-5-methoxy-2,3-dihydro-1H-indole
  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 as 5-HT1B antagonists
  申请人：SmithKline Beecham p.I.c.

  公开号：US20040176388A1

  公开（公告）日：2004-09-09

  Piperazine derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them and to their use in therapy as 5-HT 1B antagonists. W,Y,R a -R e are so defined in the application. 1

  公式(I)的吡哆醇衍生物，其制备方法，包含它们的制药组合物以及它们作为5-HT1B拮抗剂在治疗中的应用。其中，W，Y，Ra-Re在申请中有定义。
• 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 AS 5-HT1B ANTAGONISTS
  申请人：SmithKline Beecham plc

  公开号：EP1216239B1

  公开（公告）日：2004-02-11
• Potent achiral agonists of the ghrelin (growth hormone secretagogue) receptor. Part I: Lead identification
  作者：Tom D. Heightman、Jackie S. Scott、Mark Longley、Vincent Bordas、David K. Dean、Richard Elliott、Gail Hutley、Jason Witherington、Lee Abberley、Barry Passingham、Manuela Berlanga、Maite de los Frailes、Alan Wise、Ben Powney、Alison Muir、Fiona McKay、Sharon Butler、Kim Winborn、Christopher Gardner、Jill Darton、Colin Campbell、Gareth Sanger

  DOI：10.1016/j.bmcl.2007.09.067

  日期：2007.12

  High throughput screening combined with efficient datamining and parallel synthesis led to the discovery of a novel series of indolines showing potent in vitro ghrelin receptor agonist activity and acceleration of gastric emptying in rats. (c) 2007 Elsevier Ltd. All rights reserved.