1-acetyl-6-bromo-2,3-dihydro-5-<(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)methoxy>-1H-indole | 180083-89-0

• 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: 1-acetyl-6-bromo-2,3-dihydro-5-<(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)methoxy>-1H-indole
• 英文别名: 1-acetyl-6-bromo-2,3-dihydro-5-(1-methyl-1,2,3,6-tetrahydropyridin-4-ylmethoxy)-1H-indole；1-[6-bromo-5-[(1-methyl-3,6-dihydro-2H-pyridin-4-yl)methoxy]-2,3-dihydroindol-1-yl]ethanone
• CAS: 180083-89-0
• 化学式: C₁₇H₂₁BrN₂O₂
• 分子量: 365.27
• InChiKey: TUMJDRZPUGXHES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-acetyl-6-bromo-2,3-dihydro-5-<(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)methoxy>-1H-indole 在 盐酸 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 乙醇 、 苯 为溶剂， 反应 24.0h， 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：

  1,2,3,6-四氢-1-甲基-4-吡啶甲醇 、 1-(6-溴-2,3-二氢-5-羟基-1H-吲哚-1-基)乙酮 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以75%的产率得到1-acetyl-6-bromo-2,3-dihydro-5-<(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)methoxy>-1H-indole
  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

文献信息

• [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。
• Tetracyclic spiro compounds, process for their preparation and their use
  申请人：SmithKline Beecham plc

  公开号：US05972951A1

  公开（公告）日：1999-10-26

  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.

  本发明揭示了式(I)的新型哌啶衍生物，其制备过程，含有它们的制药组合物以及它们作为治疗中枢神经系统疾病的药物的用途。
• Development of a Catalytic Tributyltin Hydride Cyclisation Process
  作者：Robin P. Attrill、Mark A. Blower、Keith R. Mulholland、John K. Roberts、John E. Richardson、Martin J. Teasdale、Andre Wanders

  DOI：10.1021/op9900941

  日期：2000.3.1

  piperidine (2) from the tetrahydropyridine (4) via a radical cyclisation reaction is described. The pilot plant process involves the use of a catalytic amount of tributyltin hydride (0.14 equiv) generated in situ by the reaction of tributyltin chloride with sodium borohydride (1.1 equiv) in 2-propanol/ethanol containing azo-bis(isobutyronitrile) (AIBN). Initial laboratory conditions are described as well

  描述了通过自由基环化反应从四氢吡啶 (4) 制备螺环哌啶 (2) 的中试工厂工艺的开发。中试工厂工艺涉及使用催化量的三丁基氢化锡（0.14 equiv），该催化量是通过三丁基氯化锡与硼氢化钠（1.1 equiv）在含有偶氮双（异丁腈）（AIBN）的 2-丙醇/乙醇中反应而产生的. 描述了初始实验室条件以及转移到中试工厂时所做的更改。报告了生产的批次 (2) 中锡残留量水平的测量。
• TETRACYCLIC SPIRO COMPOUNDS, PROCESS FOR THEIR PREPARATION AND THEIR USE AS 5HT1D RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0799226B1

  公开（公告）日：2001-02-07
• US5972951A
  申请人：——

  公开号：US5972951A

  公开（公告）日：1999-10-26