1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carboxylic acid amide | 137467-14-2

• 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
• 英文名称: 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carboxylic acid amide
• 英文别名: Bisindolylmaleimide deriv. 46；1-methyl-3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indole-6-carboxamide
• CAS: 137467-14-2
• 化学式: C₂₃H₁₈N₄O₃
• 分子量: 398.421
• InChiKey: JDFHTCHKNZWWME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carbonitrile 在 sodium 1,2,3-dioxaboriran-3-olate tetrahydrate 作用下， 以 甲醇 、 水 为溶剂， 生成 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carboxylic acid amide
  参考文献：
  名称：

  Substituted pyrroles

  摘要：

  式##STR1##中的化合物，其中R.sup.1和R.sup.1'分别独立地是烷基、芳基、烯基或炔基；R.sup.2和R.sup.2'独立地是氢或烷基；R.sup.4、R.sup.5、R.sup.6和R.sup.7每个独立地是##STR2## CH.sub.2 OR.sup.10、CHO、CH.sub.2 NR.sup.11 R.sup.12、氢、卤素、氰基、烷基、羟基、烷氧基、芳氧基、卤代烷基、硝基、氨基、酰胺基、芳基氧基、单烷基氨基、双烷基氨基、烷基硫基、烷基砜基或烷基砜酰基，前提是R.sup.4、R.sup.5、R.sup.6或R.sup.7中至少有一个是氰基，##STR3## CH.sub.2 OR.sup.10、CH.sub.2 NR.sup.11 R.sup.12或CHO；R.sup.8是烷基、芳基烷基或芳基；R.sup.10是氢、烷基、芳基烷基或芳基；R.sup.11和R.sup.12独立地是氢、烷基、芳基、芳基烷基或酰基；X和Y中的一个表示O，另一个表示O、S、(H,OH)或(H,H)；以及具有公认的药用价值的酸性化合物或碱性化合物的药物可接受的前药或盐的抗增殖剂在癌症治疗中有用。

  公开号：

  US05856517A1

文献信息

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

  公开号：EP0915872B1

  公开（公告）日：2003-05-14
• US5856517A
  申请人：——

  公开号：US5856517A

  公开（公告）日：1999-01-05
• US6030994A
  申请人：——

  公开号：US6030994A

  公开（公告）日：2000-02-29
• [EN] SUBSTITUTED BISINDOLYLMALEIMIDES FOR THE INHIBITION OF CELL PROLIFERATION<br/>[FR] BISINDOLYLMALEIMIDES SUBSTITUES D'INHIBITION DE LA PROLIFERATION CELLULAIRE
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1998004552A1

  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 or alkyl; R4, R5, R6 and R7 each independently are (a), CO2R9, CH2OR10, CHO, CH2NR11R12, CON(R13)2, hydrogen, halogen, cyano, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, acylamino, aralkyloxy, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulphonyl, provided that at least one of R4, R5, R6 or R7 is cyano, (a), CO2R9, CH2OR10, CH2NR11R12, CHO or CON(R13)2; R8 is alkyl, aralkyl or aryl; R9 is alkyl, aralkyl or aryl; R10 is hydrogen, alkyl, aralkyl 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 or salts of acidic compounds of formula (I) with bases and or basic compounds of formula (I) with acids are antiproliferative agents useful in the treatment of cancer.(FR) Composés de la formule (I) dans laquelle R1 et R1' représentent indépendamment l'un de l'autre alkyle, aryle, alcényle ou alcynile; R2 and R2' représentent indépendamment l'un de l'autre hydrogène ou alkyl; R4, R5, R6 et R7 représentent indépendamment les uns des autres (a), CO2R9, CH2OR10, CHO, CH2NR11R12, CON(R13)2, hydrogène, halogène, cyano, alkyle, hydroxy, alcoxy, ariloxy, haloalkyle, nitro, amino, acylamino, aralkyloxy, monoalkylamino, dialkylamino, alkylthio, alkylsulfinyl or alkylsulfonyle, si l'un des radicaux R4, R5, R6 ou R7 représente cyano (a), CO2R9, CH2OR10, CH2NR11R12, CHO ou CON(R13)2; R8 représente alkyle, aralkyle ou aryle; R9 représente alkyle, aralkyle ou aryle; R10 représente hydrogène, alkyle, aralkyle ou aryle; R11 et R12 représentent indépendamment l'un de l'autre hydrogène, alkyle, aryle, aralkyle ou acyle; R13 représente hydrogène, alkyle, aryle ou aralkyle; et l'un des éléments X et Y signifie O et l'autre signifie O, S, (H,OH) ou (H,H); de même que des sels ou des promédicaments pharmacologiquement acceptables de composés acidifiants de la formule (I), avec des bases et/ou des composés basiques de ladite formule (I) qui constituent des agents antiproliférants utilisables dans le traitement du cancer.