4-溴-5-甲氧基吲哚-2-羧酸乙酯 | 30933-69-8

• 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: 4-溴-5-甲氧基吲哚-2-羧酸乙酯
• 英文名称: ethyl 4-bromo-5-methoxy-1H-indole-2-carboxylate
• 英文别名: Ethyl-4-bromo-5-methoxyindole-2-carboxylate；ethyl 4-bromo-5-methoxyindole-2-carboxylate；4-bromo-5-methoxy-indole-2-carboxylic acid ethyl ester；Bromo-4-methoxy-5-ethoxycarbonyl-2-indol；3-Brom-2-ethoxycarbonyl-5-methoxyindol
• CAS: 30933-69-8
• 化学式: C₁₂H₁₂BrNO₃
• 分子量: 298.136
• InChiKey: NBTXRPQZVZUOGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-溴-5-甲氧基吲哚-2-羧酸乙酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.0h， 以99.3%的产率得到4-溴-5-甲氧基吲哚-2-羧酸
  参考文献：
  名称：

  Ergoline synthons. 2. Synthesis of 1,5-dihydrobenz[cd]indol-4(3H)-ones and 1,3,4,5-tetrahydrobenz[cd]indol-4-amines

  摘要：

  DOI：

  10.1021/jo00199a004
• 作为产物：
  描述：

  5-甲氧基吲哚-2-甲酸乙酯 在 溴 、 溶剂黄146 作用下， 反应 48.0h， 生成 4-溴-5-甲氧基吲哚-2-羧酸乙酯
  参考文献：
  名称：

  SUBSTITUTED TRICYCLIC ACID DERIVATIVES AS S1P1 RECEPTOR AGONISTS USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS

  摘要：

  本发明涉及某些取代的三环酸衍生物，其具有式(I)和药用可接受的盐，并表现出有用的药理性质，例如，作为S1P1受体的激动剂。本发明还提供了含有发明的化合物的药物组合物，以及使用发明中的化合物和组合物治疗与S1P1相关的疾病的方法，例如，银屑病、类风湿性关节炎、克罗恩病、移植排斥反应、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、痤疮、心肌缺血再灌注损伤、高血压肾病、肾小球硬化症、胃炎、多发性肌炎、甲状腺炎、白癜风、肝炎、胆汁性肝硬化、微生物感染及相关疾病、病毒感染及相关疾病、由淋巴细胞介导的疾病和障碍、自身免疫性疾病、炎症性疾病和癌症。

  公开号：

  US20110160243A1

文献信息

• SUBSTITUTED TRICYCLIC ACID DERIVATIVES AS S1P1 RECEPTOR AGONISTS USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
  申请人：Jones Robert M.

  公开号：US20110160243A1

  公开（公告）日：2011-06-30

  The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.

  本发明涉及某些取代的三环酸衍生物，其具有式(I)和药用可接受的盐，并表现出有用的药理性质，例如，作为S1P1受体的激动剂。本发明还提供了含有发明的化合物的药物组合物，以及使用发明中的化合物和组合物治疗与S1P1相关的疾病的方法，例如，银屑病、类风湿性关节炎、克罗恩病、移植排斥反应、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、痤疮、心肌缺血再灌注损伤、高血压肾病、肾小球硬化症、胃炎、多发性肌炎、甲状腺炎、白癜风、肝炎、胆汁性肝硬化、微生物感染及相关疾病、病毒感染及相关疾病、由淋巴细胞介导的疾病和障碍、自身免疫性疾病、炎症性疾病和癌症。
• 2-Hydroxy-1-substituted-1,2,3,4-tetrahydro-.BETA.-carbolines. The Pictet-Spengler reaction of N-hydroxytryptamine with aldehydes.
  作者：Tohru HINO、Atsushi HASEGAWA、Jin-Jun LIU、Masako NAKAGAWA

  DOI：10.1248/cpb.38.59

  日期：——

  The Pictet-Spengler reaction of N-hydroxytryptamine (6) with various aldehydes was examined. Reduction of 3-(2-nitroethyl) indole (5) with aluminum amalgam gave 6, which was not so stable and was readily oxidized to the azoxy compound (10) in solution under an oxygen atmosphere. Reaction of 6 with saturated aldehydes gave the corresponding nitrones (11b, c) without an acid catalyst at room temperature, while the reaction with α, β-unsaturated aldehydes provided nitrones (11d, e, f) in the presence of trifluoroacetic acid. Cyclization of the nitrones with trifluoroacetic acid in methylene chloride gave the 2-hydroxy-1, 2, 3, 4-tetrahydro-β-carbolines (2) in good yields. The cyclization of the saturated nitrones proceeded rapidly, whereas the similar reaction of the unsaturated nitrones was slow. Direct Pictet-Spengler reaction of 6 with aldehydes in methylene chloride in the presence of trifluoroacetic acid gave 2a, b, c in excellent yields. Dehydration of the 2-hydroxy-β-carboline (2b) with trifluoroacetic anhydride in benzene gave the 3, 4-dihydro-β-carboline (15). 6-Bromo-5-methoxy-N-hydroxytryptamine (25) was prepared from 3-bromo-4-methyoxyaniline (17) via the indole (22). The Pictet-Spengler reaction of 25 with isovaleraldehyde gave the 2-hydroxy-tetrahydro-β-carboline (26).

  N-羟基色氨酸（6）与各种醛的Pictet-Spengler反应进行了研究。用铝汞还原3-(2-硝基乙基)吲哚（5）得到6，但该化合物不太稳定，容易在氧气气氛下氧化为氮氧化物（10）。在室温下，6与饱和醛的反应生成相应的亚硝酮（11b，c），而与α, β-不饱和醛的反应则在三氟乙酸存在下生成亚硝酮（11d，e，f）。亚硝酮与三氟乙酸在二氯甲烷中环化良好，得到了2-羟基-1, 2, 3, 4-四氢-β-卡伯林（2），产率可观。饱和亚硝酮的环化反应进展迅速，而不饱和亚硝酮的相似反应则较慢。在二氯甲烷中，6与醛的直接Pictet-Spengler反应在三氟乙酸的存在下优异地生成2a，b，c。用三氟乙酸酐在苯中脱水得到2-羟基-β-卡伯林（2b）的3, 4-二氢-β-卡伯林（15）。由3-溴-4-甲氧基苯胺（17）通过吲哚（22）合成了6-溴-5-甲氧基-N-羟基色氨酸（25）。25与异戊醛的Pictet-Spengler反应生成2-羟基-四氢-β-卡伯林（26）。
• New compounds
  申请人：Angbrant Joean

  公开号：US20080032968A1

  公开（公告）日：2008-02-07

  The present invention relates to novel compounds of formula (I): wherein m, n, R 0 , R 1 , R 2 , R 3 and R 4 are as described herein, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament against 5-HT 6 receptor-related disorders.

  本发明涉及公式（I）的新化合物：其中m，n，R0，R1，R2，R3和R4如本文所述，以及包含这些化合物的制药组合物，用于它们的制备过程，以及用于制备针对5-HT6受体相关疾病的药物的化合物的用途。
• Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
  申请人：Jones Robert M.

  公开号：US08415484B2

  公开（公告）日：2013-04-09

  The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.

  本发明涉及某些Formula (I)的取代三环酸衍生物及其药学上可接受的盐，其具有有用的药理学特性，例如作为S1P1受体的激动剂。本发明还提供了含有本发明化合物的制药组合物，以及使用本发明化合物和组合物治疗S1P1相关疾病的方法，例如牛皮癣、类风湿性关节炎、克罗恩病、移植排斥反应、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、1型糖尿病、痤疮、心肌缺血再灌注损伤、高血压性肾病、肾小球硬化、胃炎、多发性肌炎、甲状腺炎、白癜风、肝炎、胆汁性肝硬化、微生物感染及相关疾病、病毒感染及相关疾病、淋巴细胞介导的疾病和疾病、自身免疫性疾病、炎症性疾病和癌症。
• 6-Oxygenated-1,3,,4,5-Tetrahydrobenz(cd)indol-4-amines
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0162695A1

  公开（公告）日：1985-11-27

  Compounds of formula (I): in which R1 is hydrogen or C1-5 alkyl; and R2 and R3 are hydrogen, C1-4 alkyl, phenyl (CH2)n where n is 0-3, C5-6 cycloalkyl or C3-5 alkenyl; intermediates and processes for their preparation, pharmaceutical compositions containing them and their use as selective serotonin receptor antagonists.

  式(I)化合物： 其中 R1 为氢或 C1-5 烷基；R2 和 R3 为氢、C1-4 烷基、苯基 (CH2)n（其中 n 为 0-3）、C5-6 环烷基或 C3-5 烯基；制备它们的中间体和工艺、含有它们的药物组合物以及它们作为选择性血清素受体拮抗剂的用途。