(1-benzenesulfonyl-1H-indol-4-yl)-methanol | 177210-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1-benzenesulfonyl-1H-indol-4-yl)-methanol
• 英文别名: 1-(benzensulfonyl)-1H-indole-4-methanol；1-(benzenesulphonyl)-1H-indole-4-methanol；[1-(benzenesulfonyl)indol-4-yl]methanol
• CAS: 177210-24-1
• 化学式: C₁₅H₁₃NO₃S
• 分子量: 287.339
• InChiKey: ZAHJGURGEVHXHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1-benzenesulfonyl-1H-indol-4-yl)-methanol 在 盐酸 、 manganese(IV) oxide 、 ammonium acetate 、 汞 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine
  参考文献：
  名称：

  N-Arylsulfonylindole Derivatives as Serotonin 5-HT₆ Receptor Ligands

  摘要：

  A series of N-1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yI in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.

  DOI：

  10.1021/jm010943m
• 作为产物：
  描述：

  1-Benzenesulfonyl-1H-indole-4-carboxylic acid methyl ester 在 二异丁基氢化铝 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 3.0h， 以63%的产率得到(1-benzenesulfonyl-1H-indol-4-yl)-methanol
  参考文献：
  名称：

  N-Arylsulfonylindole Derivatives as Serotonin 5-HT₆ Receptor Ligands

  摘要：

  A series of N-1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yI in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.

  DOI：

  10.1021/jm010943m

文献信息

• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015086635A1

  公开（公告）日：2015-06-18

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.

  本申请揭示了根据通用式（I）定义的化合物，其中所有变量如本文所述，这些化合物抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物可用于治疗由异常B细胞激活引起的肿瘤学、自身免疫和炎症性疾病。还披露了包含通用式（I）化合物和至少一种载体、稀释剂或赋形剂的组合物。
• Preparation of benzindole compounds from naphthalene compounds
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US05498727A1

  公开（公告）日：1996-03-12

  The invention relates to a process for preparing a substituted 2-amino-benz[cd]indole of the Formula I: ##STR1## The nitro group of a substituted 1-nitro-8-cyano-naphthalene compound is reduced to an amine group to form a substituted 1-amino-8-cyano-naphthalene compound, which is cyclized to form the substituted 2-amino-benz[cd]indole. The reduction and cyclization may be effected in a one-pot procedure using a reducing agent such as stannous chloride, which generates an acid that cyclizes the reduction product. The syntheses of the 1-nitro-8-cyanonaphthalene compound and its precursors are also described.

  该发明涉及一种制备Formula I的取代2-氨基苯[cd]吲哚的过程：##STR1## 取代的1-硝基-8-氰基萘烯化合物的硝基团被还原为胺基，形成取代的1-氨基-8-氰基萘烯化合物，然后将其环化形成取代的2-氨基苯[cd]吲哚。还可以使用还原剂（如氯化亚锡）在一个锅中进行还原和环化。描述了1-硝基-8-氰基萘烯化合物及其前体的合成方法。
• Indole and indoline derivatives as 5-HT6 selective ligands
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06187805B1

  公开（公告）日：2001-02-13

  Three classes of indole and indoline derivatives are disclosed as ligands selective for the 5-HT6 receptors, and hence of value in the treatment or prevention of CNS disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, depression and anxiety. A particular class, 1-substituted-4-(&ohgr;-N,N-dialkyl-aminoalkyl)indoles, are claimed as novel compounds.

  揭示了三类吲哚和吲哚啉衍生物作为选择性结合到5-HT6受体的配体，因此在治疗或预防中枢神经系统疾病方面具有价值，包括阿尔茨海默病、帕金森病、精神分裂症、抑郁症和焦虑症。其中一类称为1-取代-4-(&ohgr;-N,N-二烷基氨基烷基)吲哚，被称为新型化合物。
• Cyano naphthalene compounds
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US05545744A1

  公开（公告）日：1996-08-13

  The invention relates to a process for preparing a substituted 2-amino-benz[cd]indole of the Formula I: ##STR1## The nitro group of a substituted 1-nitro-8-cyano-naphthalene compound is reduced to an amine group to form a substituted 1-amino-8-cyano-naphthalene compound, which is cyclized to form the substituted 2-amino-benz[cd]indole. The reduction and cyclization may be effected in a one-pot procedure using a reducing agent such as stannous chloride, which generates an acid that cyclizes the reduction product. The syntheses of the 1-nitro-8-cyano-naphthalene compound and its precursors are also described.

  本发明涉及一种制备取代的2-氨基苯[cd]吲哚（化学式I）的方法：##STR1## 将取代的1-硝基-8-氰基萘化合物的硝基还原为胺基，形成取代的1-氨基-8-氰基萘化合物，该化合物环化形成取代的2-氨基苯[cd]吲哚。还原和环化可以在一个锅中使用还原剂（例如氯化亚锡）进行，该还原剂产生一个酸，使还原产物环化。还描述了1-硝基-8-氰基萘化合物及其前体的合成方法。
• Inhibitors of bruton's tyrosine kinase
  申请人：Hoffmann-La Roche Inc.

  公开号：US10093657B2

  公开（公告）日：2018-10-09

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.

  本申请公开了根据通式（I）：其中所有变量的定义如本文所述，可抑制 Btk 的化合物。本文公开的化合物可用于调节 Btk 的活性，治疗与 Btk 活性过高有关的疾病。这些化合物可用于治疗由异常 B 细胞活化引起的肿瘤、自身免疫和炎症性疾病。还公开了含有式（I）化合物和至少一种载体、稀释剂或赋形剂的组合物。