3-carboxy-4-pyridyl 1'-(phenylsulfonyl)-5'-methoxy-2'-indolyl ketone | 143706-87-0

• 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: 3-carboxy-4-pyridyl 1'-(phenylsulfonyl)-5'-methoxy-2'-indolyl ketone
• 英文别名: 1-(phenylsulfonyl)-5-methoxyindol-2-yl 3-carboxy-4-pyridyl ketone；4-[[5-Methoxy-1-(phenyl sulfonyl)-1H-indol-2-yl]carbonyl]-3-pyridine-carboxylic acid；4-[1-(Benzenesulfonyl)-5-methoxyindole-2-carbonyl]pyridine-3-carboxylic acid
• CAS: 143706-87-0
• 化学式: C₂₂H₁₆N₂O₆S
• 分子量: 436.445
• InChiKey: RVOBNJGKSCIECV-UHFFFAOYSA-N

物化性质

• 沸点：
  739.7±70.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-carboxy-4-pyridyl 1'-(phenylsulfonyl)-5'-methoxy-2'-indolyl ketone 在 乙酸酐 、 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 31.0h， 生成 8-methoxyindolo<1,2-b><2,7>naphthyridine-5,12-quinone
  参考文献：
  名称：

  A versatile and efficient construction of the 6H-pyrido[4,3-b]carbazole ring system. Syntheses of the antitumor alkaloids ellipticine, 9-methoxyellipticine, and olivacine, and their analogs

  摘要：

  A general and efficient synthesis of the 6H-pyrido[4,3-b]carbazole ring system is described, in which the key steps are (1) regioselective acylation of a 2-lithio-1-(phenylsulfonyl)indole (14) with 3,4-pyridinedicarboxylic acid anhydride (10), (2) cyclization of the deprotected keto acid 17 to keto lactam 19 with acetic anhydride, and (3) the addition of methyllithium to give, after reduction of the intermediate diol 23 with sodium borohydride, the target ring system. In this fashion, ellipticine (1a), 9-methoxyellipticine (1b), and 9-hydroxyellipticine (1c) were synthesized in excellent overall yields from indole. The use of Superhydride, in place of 1 equiv of methyllithium, provided a synthesis of olivacine (2), and the use of phthalic anhydride in the sequence allowed for the preparation of 6,11-dimethylbenzo[b]carbazole (48). The overall yields of ellipticine (1a) (54%) and 9-methoxyellipticine (1b) (47%) in six steps from their respective indoles represent one of the most efficient syntheses of these antitumor alkaloids.

  DOI：

  10.1021/jo00048a022
• 作为产物：
  描述：

  4-硝基间甲苯酚 在 palladium on activated charcoal 正丁基锂 、 氢气 、 sodium methylate 、 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， -100.0~25.0 ℃ 、303.98 kPa 条件下， 反应 54.0h， 生成 3-carboxy-4-pyridyl 1'-(phenylsulfonyl)-5'-methoxy-2'-indolyl ketone
  参考文献：
  名称：

  A versatile and efficient construction of the 6H-pyrido[4,3-b]carbazole ring system. Syntheses of the antitumor alkaloids ellipticine, 9-methoxyellipticine, and olivacine, and their analogs

  摘要：

  A general and efficient synthesis of the 6H-pyrido[4,3-b]carbazole ring system is described, in which the key steps are (1) regioselective acylation of a 2-lithio-1-(phenylsulfonyl)indole (14) with 3,4-pyridinedicarboxylic acid anhydride (10), (2) cyclization of the deprotected keto acid 17 to keto lactam 19 with acetic anhydride, and (3) the addition of methyllithium to give, after reduction of the intermediate diol 23 with sodium borohydride, the target ring system. In this fashion, ellipticine (1a), 9-methoxyellipticine (1b), and 9-hydroxyellipticine (1c) were synthesized in excellent overall yields from indole. The use of Superhydride, in place of 1 equiv of methyllithium, provided a synthesis of olivacine (2), and the use of phthalic anhydride in the sequence allowed for the preparation of 6,11-dimethylbenzo[b]carbazole (48). The overall yields of ellipticine (1a) (54%) and 9-methoxyellipticine (1b) (47%) in six steps from their respective indoles represent one of the most efficient syntheses of these antitumor alkaloids.

  DOI：

  10.1021/jo00048a022

文献信息

• Use of Indole Derivatives as Nurr-1 Activators for the Application Thereof as a Medicament for the Treatment of Parkinson's Disease
  申请人：Amaudrut Jerome

  公开号：US20120232070A1

  公开（公告）日：2012-09-13

  Compounds derived from indole, notably useful in therapeutics, selected from: i) the compounds of formula: and ii) the pharmaceutically acceptable salts of the compounds of formula (I); in which R1, R2, R3, R4, R5, R6, R8, R9 and Cy have defined meanings, and the use of such compounds in pharmaceuticals for the treatment of neurodegenerative diseases, particularly Parkinson's disease.

  从吲哚衍生的化合物，在治疗中特别有用，从以下中选择： i) 公式的化合物： 和 ii) 公式（I）的化合物的药用盐； 其中R1、R2、R3、R4、R5、R6、R8、R9和Cy具有定义的含义，并且在制药中使用这些化合物治疗神经退行性疾病，特别是帕金森病。
• N-Methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines
  作者：John C. Ruckdeschel、Sandeep P. Modi、Wageeh El-Hamouly、Enrico Portuese、Sydney Archer

  DOI：10.1021/jm00104a011

  日期：1992.12

  A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 muM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 muM). N-methylcarbamates of 9-methoxy-6H-pyrido[4,3-b] carbazole 1-, 5-, and 11-methanols gave IC50 values ranging from 0.02 to 0.11 muM against N417, H460, and H358 and were only slightly less effective against H69.
• A versatile and efficient construction of the 6H-pyrido[4,3-b]carbazole ring system. Syntheses of the antitumor alkaloids ellipticine, 9-methoxyellipticine, and olivacine, and their analogs
  作者：Gordon W. Gribble、Mark G. Saulnier、Judy A. Obaza-Nutaitis、Daniel M. Ketcha

  DOI：10.1021/jo00048a022

  日期：1992.10

  A general and efficient synthesis of the 6H-pyrido[4,3-b]carbazole ring system is described, in which the key steps are (1) regioselective acylation of a 2-lithio-1-(phenylsulfonyl)indole (14) with 3,4-pyridinedicarboxylic acid anhydride (10), (2) cyclization of the deprotected keto acid 17 to keto lactam 19 with acetic anhydride, and (3) the addition of methyllithium to give, after reduction of the intermediate diol 23 with sodium borohydride, the target ring system. In this fashion, ellipticine (1a), 9-methoxyellipticine (1b), and 9-hydroxyellipticine (1c) were synthesized in excellent overall yields from indole. The use of Superhydride, in place of 1 equiv of methyllithium, provided a synthesis of olivacine (2), and the use of phthalic anhydride in the sequence allowed for the preparation of 6,11-dimethylbenzo[b]carbazole (48). The overall yields of ellipticine (1a) (54%) and 9-methoxyellipticine (1b) (47%) in six steps from their respective indoles represent one of the most efficient syntheses of these antitumor alkaloids.