1-(6-溴-2,3-二氢-5-羟基-1H-吲哚-1-基)乙酮 | 42443-15-2

• 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
• 中文名称: 1-(6-溴-2,3-二氢-5-羟基-1H-吲哚-1-基)乙酮
• 英文名称: 1-acetyl-6-bromo-2,3-dihydro-1H-indol-5-ol
• 英文别名: 1-(6-bromo-5-hydroxy-2,3-dihydroindol-1-yl)ethanone；1-acetyl-6-bromo-5-hydroxyindoline；1-acetyl-6-bromoindolin-5-ol；1-(6-Bromo-5-hydroxy-2,3-dihydro-1H-indol-1-yl)ethan-1-one
• CAS: 42443-15-2
• 化学式: C₁₀H₁₀BrNO₂
• 分子量: 256.099
• InChiKey: YLMUSSQQLTWOLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(6-溴-2,3-二氢-5-羟基-1H-吲哚-1-基)乙酮 在 盐酸 、 偶氮二异丁腈 、 三正丁基氢锡 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 苯 为溶剂， 反应 25.0h， 生成 1'-methyl-2,3,6,7-tetrahydrospiroindole-3,4'-piperidine>
  参考文献：
  名称：

  The Selective 5-HT_1B Receptor Inverse Agonist 1‘-Methyl-5-[[2‘-methyl-4‘- (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo

  摘要：

  5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively Linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1D beta and 5-HT1D alpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

  DOI：

  10.1021/jm970457s
• 作为产物：
  描述：

  1-乙酰基-5-硝基二氢吲哚 在 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 palladium on activated charcoal 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 、 异丙醇 为溶剂， 反应 15.0h， 生成 1-(6-溴-2,3-二氢-5-羟基-1H-吲哚-1-基)乙酮
  参考文献：
  名称：

  [EN] BROMODOMAIN INHIBITOR
  [FR] INHIBITEUR DE BROMODOMAINE

  摘要：

  公开号：

  WO2016168682A3

文献信息

• Novel and Selective 5-HT_2C/2B Receptor Antagonists as Potential Anxiolytic Agents:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling of Substituted 1-(3-Pyridylcarbamoyl)indolines
  作者：Steven M. Bromidge、Steven Dabbs、David T. Davies、D. Malcolm Duckworth、Ian T. Forbes、Peter Ham、Graham E. Jones、Frank D. King、Damian V. Saunders、Susannah Starr、Kevin M. Thewlis、Paul A. Wyman、Frank E. Blaney、Christopher B. Naylor、Fiona Bailey、Thomas P. Blackburn、Vicky Holland、Guy A. Kennett、Graham J. Riley、Martyn D. Wood

  DOI：10.1021/jm970741j

  日期：1998.5.1

  The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously

  报道了一系列新的取代的1-（3-吡啶基氨基甲酰基）二氢吲哚的合成，生物活性和分子模型。这些化合物是先前公开的吲哚脲1（SB-206553）的等排体，并说明了在5-HT2C / 2B受体拮抗剂的背景下使用芳香族脱位取代稠合的五元环。通过靶向先前鉴定为在5-HT2C受体上空间允许但在5-HT2A受体上不允许的空间区域，我们已经鉴定出许多化合物，它们是迄今报道的最有效和选择性最强的5-HT2C / 2B受体拮抗剂。根据其整体生物学特征选择了46（SB-221284）作为新的潜在非镇静抗焦虑药进行进一步评估。
• Method for synthesis of aryl difluoromethyl ethers
  申请人：SmithKline Beecham Corporation

  公开号：US05731477A1

  公开（公告）日：1998-03-24

  This invention relates to a method for preparing difluoromethyl ethers, thiols and amines without using chlorofluorocarbon gases. The intermediates prepared by this method can be used to make certain compounds which act as PDE IV inhibitors which are useful for treating asthma and other diseases implicated with the PDE IV isozyme.

  这项发明涉及一种制备二氟甲基醚、硫醇和胺的方法，而不使用氯氟烃气体。通过这种方法制备的中间体可用于制备某些化合物，这些化合物作为PDE IV抑制剂，对治疗哮喘和其他与PDE IV同工酶有关的疾病有用。
• [EN] TETRACYCLIC SPIRO COMPOUNDS, PROCESS FOR THEIR PREPARATION AND THEIR USE AS 5HT1D RECEPTOR ANTAGONISTS<br/>[FR] COMPOSES SPIRO TETRACYCLIQUES, PROCEDES DE PREPARATION ET UTILISATION COMME ANTAGONISTES DU RECEPTEUR 5HT1D
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1996019477A1

  公开（公告）日：1996-06-27

  (EN) Novel piperidine derivatives of formula (I), processes for their preparation, pharmaceutical compositions containing them and their use as medicaments for the treatment of CNS disorders are disclosed.(FR) La présente invention concerne de nouveaux dérivés de pipéridine représentés par la formule générale (I), des procédés permettant leur préparation, des compositions pharmaceutiques à base de ces dérivés, ainsi que leur utilisation en tant que médicaments destinés au traitement de troubles du système nerveux central.

  （中文）本发明涉及一种新的哌啶衍生物，其化学式为（I），其制备方法，包含它们的药物组合物以及它们作为治疗中枢神经系统疾病的药物的使用。
• [EN] PIPERAZINE DERIVATIVES AS 5-HT1B ANTAGONISTS<br/>[FR] DERIVES DE PIPERAZINE UTILISES EN TANT QU'ANTAGONISTES DE 5-HT1B
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2001023374A1

  公开（公告）日：2001-04-05

  Piperazine derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them and to their use in therapy as 5-HT1B antagonists. W,Y,Ra-Reare so defined in the application.

  式(I)的哌嗪衍生物，其制备方法，包含它们的制药组合物以及作为5-HT1B拮抗剂在治疗中的用途。W，Y，Ra-Re在申请中有定义。
• 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。