1-methyl-7-nitroindole-3-glyoxylyl chloride | 137467-18-6

• 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-methyl-7-nitroindole-3-glyoxylyl chloride
• 英文别名: 2-(1-Methyl-7-nitroindol-3-yl)-2-oxoacetyl chloride
• CAS: 137467-18-6
• 化学式: C₁₁H₇ClN₂O₄
• 分子量: 266.641
• InChiKey: ADURISYFQJCUOT-UHFFFAOYSA-N

物化性质

• 沸点：
  480.2±48.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  84.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-7-nitroindole-3-glyoxylyl chloride 在 palladium on activated charcoal ammonium hydroxide 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0~140.0 ℃ 、101.33 kPa 条件下， 反应 26.0h， 生成 3-(7-(acetylamino)-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)pyrrole-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024
• 作为产物：
  描述：

  7-硝基吲哚 在 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 1-methyl-7-nitroindole-3-glyoxylyl chloride
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024

文献信息

• SUBSTITUTED BISINDOLYLMALEIMIDES FOR THE INHIBITION OF CELL PROLIFERATION
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0915870A1

  公开（公告）日：1999-05-19
• US6228877B1
  申请人：——

  公开号：US6228877B1

  公开（公告）日：2001-05-08
• [EN] SUBSTITUTED BISINDOLYLMALEIMIDES FOR THE INHIBITION OF CELL PROLIFERATION<br/>[FR] BIS-INDOLYLMALEIMIDES SUBSTITUES DESTINES A INHIBER LA PROLIFERATION CELLULAIRE
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1998004551A1

  公开（公告）日：1998-02-05

  (EN) Compounds of formula (I) wherein: R1 and R1' are independently alkyl, aryl, alkenyl or alkynyl; R2 and R2' are independently hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonyl-aminoalkyl, mercaptoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylthio or alkylsulphinyl; R4, R5, R6, R7, R4', R5', R6' and R7' each independently are hydrogen, formula (II), CO2R9, CH2OR10, CHO, CH2NR11R12, CON(R13)2, halogen, cyano, aryl, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, aralkyloxy, acylamino, monoalkylamino, dialkylamino, thio, alkylthio, alkylsulphinyl, alkylsulphonyl, arylsulphinyl, azide, phosphate or phosphonate provided that at least one of R4, R5, R6 and R7 and at least one of R4', R5', R6' and R7' are other than hydrogen, with the proviso that when R6 is methoxy, R5 or R5' are not methoxy; R8 is alkyl or aryl; R9 is alkyl or aryl; R10 is hydrogen, alkyl or aryl; R11 and R12 are independently hydrogen, alkyl, aryl, aralkyl or acyl; R13 is hydrogen, alkyl, aryl or aralkyl; and one of X and Y signifies O and the other signifies O, S, (H,OH) or (H,H); as well as pharmaceutically acceptable prodrugs therefor or pharmaceutically acceptable salts of acidic compounds of formula (I) with basis or basic compounds of formula (I) with acids are antiproliferative agents useful in the treatment of cancer.(FR) L'invention concerne des composés de formule (I), dans laquelle R1 et R1' sont indépendamment alkyle, aryle, alcényle ou alkynyle; R2 et R2' sont indépendamment hydrogène, alkyle, aralkyle, alcoxyalkyle, hydroxyalkyle, haloalkyle, aminoalkyle, monoalkylaminoalkyle, dialkylaminoalkyle, acylaminoalkyle, alkylsulfonylaminoalkyle, arylsulfonylaminoalkyle, mercaptoalkyle, alkylthioalkyle, carboxyalkyle, alcoxycarbonylalkyle, aminocarbonylalkyle, alkylthio ou alkylsulfinyle; R4, R5, R6, R7, R4', R5', R6' et R7' sont indépendamment hydrogène, (II), CO2R9, CH2OR10, CHO, CH2NR11R12, CON(R13)2, halogène, cyano, aryle, alkyle, hydroxy, alcoxy, aryloxy, haloalkyle, nitro, amino, aralkyloxy, acylamino, monoalkylamino, dialkylamino, thio, alkylthio, alkylsulfinyle, alkylsulfonyle, arylsulfinyle, azide, phosphate ou phosphonate, à condition qu'au moins R4, R5, R6 et/ou R7 et au moins R4', R5', R6' et/ou R7' soient autres qu'hydrogène, à condition que quand R6 est méthoxy, R5 ou R5' ne soit pas méthoxy; R8 est alkyle ou aryle; R9 est alkyle ou aryle; R10 est hydrogène, alkyle ou aryle; R11 et R12 sont indépendamment hydrogène, alkyle, aryle, aralkyle ou acyle; R13 est hydrogène, alkyle, aryle ou aralkyle; et X ou Y signifie O et l'autre signifie O, S, (H,OH) ou (H,H). L'invention concerne également des promédicaments pharmaceutiquement acceptables pour ces composés, ou des sels pharmaceutiquement acceptables de composés acides de formule (I) avec des bases ou de composés basiques de formule (I) avec des acides. Ces composés sont des agents antiprolifératifs utiles dans le traitement du cancer.
• Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides
  作者：Peter D. Davis、Christopher H. Hill、Geoffrey Lawton、John S. Nixon、Sandra E. Wilkinson、Steven A. Hurst、Elizabeth Keech、Susan E. Turner

  DOI：10.1021/jm00079a024

  日期：1992.1

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).