[2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1'-联苯基]-4-基](2,5,6,7-四氢-1'-甲基螺[3H-呋喃并[2,3-F]吲哚-3,4'-哌啶]-5-基)甲酮 | 180083-23-2

• 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: [2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1'-联苯基]-4-基](2,5,6,7-四氢-1'-甲基螺[3H-呋喃并[2,3-F]吲哚-3,4'-哌啶]-5-基)甲酮
• 英文名称: 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)
• 英文别名: SB 224289；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]；[4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl]-(1'-methylspiro[6,7-dihydro-2H-furo[2,3-f]indole-3,4'-piperidine]-5-yl)methanone；SB224289；SB‐224289；SB-224289；(2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)(1'-methyl-6,7-dihydrospiro[furo[2,3-f]indole-3,4'-piperidin]-5(2H)-yl)methanone
• CAS: 180083-23-2
• 化学式: C₃₂H₃₂N₄O₃
• 分子量: 520.631
• InChiKey: ATQMRMGXINTJHV-UHFFFAOYSA-N

物化性质

• 熔点：
  >280℃
• 沸点：
  724.8±70.0 °C(Predicted)
• 密度：
  1.34
• 溶解度：
  在DMSO中的溶解度为4.5 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  39
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  71.7
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 储存条件：
  存放在室温、干燥且密封的环境中。

制备方法与用途

SB-224289 是一种选择性 5-HT1B 受体拮抗剂，具有抗焦虑的作用。

反应信息

• 作为反应物：
  描述：

  [2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1'-联苯基]-4-基](2,5,6,7-四氢-1'-甲基螺[3H-呋喃并[2,3-F]吲哚-3,4'-哌啶]-5-基)甲酮 在 m-chloroperoxybenzoic acid 作用下， 以 氯仿 为溶剂， 以39%的产率得到1'-Methyl-5-(2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carbonyl)-1'-oxo-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]
  参考文献：
  名称：

  Tetracyclic spiro compounds, process for their preparation and their use

  摘要：

  披露了公式(I)的新哌啶衍生物，它们的制备过程，含有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应用。

  公开号：

  US05972951A1
• 作为产物：
  描述：

  2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 73.0h， 生成 [2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1'-联苯基]-4-基](2,5,6,7-四氢-1'-甲基螺[3H-呋喃并[2,3-F]吲哚-3,4'-哌啶]-5-基)甲酮
  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 AS 5HT1D RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0799226B1

  公开（公告）日：2001-02-07
• AZASPIRODERIVATIVES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0889893A1

  公开（公告）日：1999-01-13
• METHODS FOR TREATING NEUROLOGICAL DISORDERS OR DAMAGE
  申请人：Tyers Mike

  公开号：US20090076019A1

  公开（公告）日：2009-03-19

  A clonogenic neurosphere assay is described that carries out high throughput screens (HTS) to identify potent and/or selective modulators of proliferation, differentiation and/or renewal of neural precursor cells, neural progenitor cells and/or self-renewing and multipotent neural stem cells (NSCs). Compositions comprising the identified modulators and methods of using the modulators and compositions, in particular to treat neurological disorders (e.g. brain or CNS cancer) or damage are also disclosed.
• US5972951A
  申请人：——

  公开号：US5972951A

  公开（公告）日：1999-10-26