6-[(R)-2-(2-bromo-ethyl)pyrrolidine-1-sulfonyl]-1H-indole | 446020-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-[(R)-2-(2-bromo-ethyl)pyrrolidine-1-sulfonyl]-1H-indole
• 英文别名: 6-[(2R)-2-(2-bromoethyl)pyrrolidin-1-yl]sulfonyl-1H-indole
• CAS: 446020-63-9
• 化学式: C₁₄H₁₇BrN₂O₂S
• 分子量: 357.271
• InChiKey: SGCCUFPBPJGEQA-GFCCVEGCSA-N

物化性质

• 沸点：
  534.9±46.0 °C(Predicted)
• 密度：
  1.551±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4’-哌啶基)-1H-吲哚 、 6-[(R)-2-(2-bromo-ethyl)pyrrolidine-1-sulfonyl]-1H-indole 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 3-[1-[2-[(2R)-1-(1H-indol-6-ylsulfonyl)pyrrolidin-2-yl]ethyl]piperidin-4-yl]-1H-indole
  参考文献：
  名称：

  SB-656104-A: A novel 5-HT7 receptor antagonist with improved In vivo properties

  摘要：

  A focused SAR study around the previously reported selective 5-HT7 receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00690-x
• 作为产物：
  描述：

  2-[(R)-1-(1H-Indole-6-sulfonyl)-pyrrolidin-2-yl]-ethanol 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 6-[(R)-2-(2-bromo-ethyl)pyrrolidine-1-sulfonyl]-1H-indole
  参考文献：
  名称：

  SB-656104-A: A novel 5-HT7 receptor antagonist with improved In vivo properties

  摘要：

  A focused SAR study around the previously reported selective 5-HT7 receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00690-x

文献信息

• [EN] SULFONAMIDE COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] COMPOSES DE SULFONAMIDE, PREPARATION ET UTILISATION
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2002062788A1

  公开（公告）日：2002-08-15

  Compounds possessing 5HT7 activity of formula (I) or a pharmaceutically acceptable salt thereof are disclosed (Formula I), in which X is a 5 or 6 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitroxygen and sulfur; R2 is alogen, C1-6alkyl, haloC1-6alkyl, hydroxy, C1-6alkoxy or C1-6alkylthio; R3 is hydrogen, C1-6alkyl, hydroxy or oxo; m is 0, 1 or 2; p is 0, 1 or 2; n is 1 or 2; R4 and R5 are both hydrogen, or R4 and R5 combine together to form a further group: -(CH2)q- where q is 2 or 3; D is a single bond, C1-4alkylene, C=O or oxygen; Z is either a group (a) (Formula II), in which R1 is halogen, C1-6alkyl, cyano, haloC1-6cycloalkyl, C1-6alkoxy, hadroxy, amino, mono- or di-C1-6alkylamino, acylamino, nitro, carboxy, C1-6alkoxycarbonyl, C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, sulfamoyl, mono- and di-C1-6alkylsulfamoyl, carbamoyl, mono- or di-C1-6alkylcarbamoyl, C1-6alkylsulfonamido, aryl, arylC1-6alkyl, arylC1-6alkoxy, aryloxy or arylthio, and y is 0, 1, 2 or 3; or a group (b) (formula III), in which P is a 5 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur; R8 is hydrogen, C1-6alkyl, hydroxy or oxo; R6 and R7 form the residue of a phenyl ring or a 6 membered heteroaryl ring comprising from one to three heteroatoms selected from nitrogen, oxygen and sulfur and optionally substituted with one or two substitutents which may be the same or different and selected from the group consisting of halogen, C1-6alkyl, cyano, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, hydroxy, amino, mono- or di-C1-6alkylamino, acylamino, nitro, carboxy, C1-6alkoxycarbonyl, C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, sulfamoyl, mono- and di-C1-6alkylsufamoyl, carbamoyl, mono- and di-C1-6alkylcarbamoyl, C1-6alkylsulfonamido, arylsulfonamido, aryl, arylC1-6alkyl, arylC1-6alkoxy, aryloxy and arylthio. Also disclosed are processes for preparation of the compounds, and uses in the treatment of CNS and other disorders.

  公开了具有5HT7活性的化合物的公式（I）或其药学上可接受的盐（公式I），其中X是含有1至3个氧、硝基氧和硫的杂环5或6元环，R2是卤素、C1-6烷基、卤代C1-6烷基、羟基、C1-6烷氧基或C1-6烷基硫基；R3是氢、C1-6烷基、羟基或氧代；m为0、1或2；p为0、1或2；n为1或2；R4和R5都是氢，或者R4和R5结合形成进一步的基团：-(CH2)q-，其中q为2或3；D是单键、C1-4烷基、C=O或氧代；Z是一个群（a）（公式II），其中R1是卤素、C1-6烷基、氰基、卤代C1-6环烷基、C1-6烷氧基、羟基、氨基、单-或双C1-6烷基氨基、酰胺基、硝基、羧基、C1-6烷氧羰基、C1-6烷基硫基、C1-6烷基亚磺酰基、C1-6烷基磺酰基、磺酰胺基、单-和双C1-6烷基磺酰胺基、氨基甲酰基、单-或双C1-6烷基氨基甲酰基、C1-6烷基磺酰胺基、芳基、芳基C1-6烷基、芳基C1-6烷氧基、芳氧基或芳硫基，y为0、1、2或3；或者一个群（b）（公式III），其中P是含有1至3个氧、氮和硫的杂环5元环，R8是氢、C1-6烷基、羟基或氧代；R6和R7形成苯环或含有1至3个氮、氧和硫的6元杂环的残基，并且可以选择地被一个或两个取代基取代，这些取代基可以相同或不同，并且选择自以下群：卤素、C1-6烷基、氰基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、羟基、氨基、单-或双C1-6烷基氨基、酰胺基、硝基、羧基、C1-6烷氧羰基、C1-6烷基硫基、C1-6烷基亚磺酰基、C1-6烷基磺酰基、磺酰胺基、单-和双C1-6烷基磺酰胺基、氨基甲酰基、单-或双C1-6烷基氨基甲酰基、C1-6烷基磺酰胺基、芳基磺酰胺基、芳基、芳基C1-6烷基、芳基C1-6烷氧基、芳氧基和芳硫基。还公开了制备这些化合物的方法，并在中枢神经系统和其他疾病的治疗中使用的用途。
• Sulfonamide compounds, their preparation and use
  申请人：——

  公开号：US20040267010A1

  公开（公告）日：2004-12-30

  Compounds possessing 5HT7 activity of formula (I) or a pharmaceutically acceptable salt thereof are disclosed: 1 in which X is a 5 or 6 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur; R 2 is halogen, C 1-6 alkyl, haloC 1-6 alkyl, hydroxy, C 1-6 alkoxy or C 1-6 alkylthio; R 3 is hydrogen, C 1-6 alkyl, hydroxy or oxo; m is 0, 1 or 2; p is 0, 1 or 2; n is 1 or 2; R 4 and R 5 are both hydrogen, or R 4 and R 5 combine together to form a further group: —(CH 2 )q- where q is 2 or 3; D is a single bond, C 1-4 alkylene, C═O or oxygen; Z is either a group (a): 2 in which R 1 is halogen, C 1 - 6 alkyl, cyano, haloC 1-6 alkyl, C 3 - 7 cycloalkyl, C 1 - 6 alkoxy, hydroxy, amino, mono- or di-C 1 - 6 alkylamino, acylamino, nitro, carboxy, C 1 - 6 alkoxycarbonyl, C 1 - 6 alkylthio, C 1 - 6 alkylsulfinyl, C 1 - 6 alkylsulfonyl, sulfamoyl, mono- and di-C 1 - 6 alkylsulfamoyl, carbamoyl, mono- or di-C 1 - 6 alkylcarbamoyl, C 1 - 6 alkylsulfonamido, arylsulfonamido, aryl, arylC 1 - 6 alkyl, arylC 1 - 6 alkoxy, aryloxy or arylthio, and y is 0, 1, 2 or 3; or a group (b): 3 in which P is a 5 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur; R 8 is hydrogen, C 1-6 alkyl, hydroxy or oxo; R 6 and R 7 form the residue of a phenyl ring or a 6 membered heteroaryl ring comprising from one to three heteroatoms selected from nitrogen, oxygen and sulfur and optionally substituted with one or two substitutents which may be the same or different and selected from the group consisting of halogen, C 1 - 6 alkyl, cyano, haloC 1-6 alkyl, C 3 - 7 cycloalkyl, C 1 - 6 alkoxy, hydroxy, amino, mono- or di-C 1 - 6 alkylamino, acylamino, nitro, carboxy, C 1 - 6 alkoxycarbonyl, C 1 - 6 alkylthio, C 1 - 6 alkylsulfinyl, C 1 - 6 alkylsulfonyl, sulfamoyl, mono- and di-C 1 - 6 alkylsulfamoyl, carbamoyl, mono- and di-C 1 - 6 alkylcarbamoyl, C 1 - 6 alkylsulfonamido, arylsulfonamido, aryl, arylC 1 - 6 alkyl, arylC 1 - 6 alkoxy, aryloxy and arylthio. Also disclosed are processes for preparation of the compounds, and uses in the treatment of CNS and other disorders.

  本文披露了具有5HT7活性的化合物的公式（I）或其药学上可接受的盐：其中X是含有1至3个氧、氮和硫杂原子的5或6元杂环环，R2为卤素、C1-6烷基、卤代C1-6烷基、羟基、C1-6烷氧基或C1-6烷基硫醚；R3为氢、C1-6烷基、羟基或氧代；m为0、1或2；p为0、1或2；n为1或2；R4和R5均为氢，或R4和R5结合形成另一基团：-（CH2）q-其中q为2或3；D为单键、C1-4烷基、C═O或氧；Z为以下两种基团之一：（a）其中R1为卤素、C1-6烷基、氰基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、羟基、氨基、单-或双C1-6烷基氨基、酰胺基、硝基、羧基、C1-6烷氧羰基、C1-6烷基硫醇基、C1-6烷基亚磺酰基、磺酰胺基、单-和双C1-6烷基磺酰胺基、氨基甲酰基、单-或双C1-6烷基氨基甲酰基、C1-6烷基磺酰胺基、芳基磺酰胺基、芳基、芳基C1-6烷基、芳基C1-6烷氧基、芳氧基或芳硫醚基，y为0、1、2或3；或（b）其中P为含有1至3个氧、氮和硫杂原子的5元杂环环，R8为氢、C1-6烷基、羟基或氧代；R6和R7形成苯环或含有从一个到三个氮、氧和硫杂原子的6元杂环环的残基，且可选择地被一个或两个取代基取代，所述取代基可能相同或不同，并从以下基团中选择：卤素、C1-6烷基、氰基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、羟基、氨基、单-或双C1-6烷基氨基、酰胺基、硝基、羧基、C1-6烷氧羰基、C1-6烷基硫醇基、C1-6烷基亚磺酰基、磺酰胺基、单-和双C1-6烷基磺酰胺基、氨基甲酰基、单-或双C1-6烷基氨基甲酰基、C1-6烷基磺酰胺基、芳基磺酰胺基、芳基、芳基C1-6烷基、芳基C1-6烷氧基、芳氧基或芳硫醚基。本文还披露了制备这些化合物的方法以及在治疗中枢神经系统和其他疾病中的用途。
• SULFONAMIDE COMPOUNDS, THEIR PREPARATION AND USE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1355902A1

  公开（公告）日：2003-10-29
• SB-656104-A: A novel 5-HT7 receptor antagonist with improved In vivo properties
  作者：Ian T. Forbes、Sara Douglas、Andrew D. Gribble、Robert J. Ife、Andrew P. Lightfoot、Ashley E. Garner、Graham J. Riley、Phillip Jeffrey、Alexander J. Stevens、Tania O. Stean、David R. Thomas

  DOI：10.1016/s0960-894x(02)00690-x

  日期：2002.11

  A focused SAR study around the previously reported selective 5-HT7 receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A. (C) 2002 Elsevier Science Ltd. All rights reserved.