(4-methoxy-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride | 143137-55-7

• 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: (4-methoxy-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride
• 英文别名: 1-methyl-4-methoxy-α-oxo-3-indoleacetyl chloride；2-(4-Methoxy-1-methylindol-3-yl)-2-oxoacetyl chloride
• CAS: 143137-55-7
• 化学式: C₁₂H₁₀ClNO₃
• 分子量: 251.669
• InChiKey: MBMZNVBRAUARDX-UHFFFAOYSA-N

物化性质

• 沸点：
  428.6±48.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-methoxy-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride 在 ammonium hydroxide 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-(4-methoxy-1-methyl-3-indolyl)-4-(1-methyl-3-indolyl)-1H-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：

  4-甲氧基吲哚 在 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 (4-methoxy-1-methyl-1H-indol-3-yl)-oxo-acetyl 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 pyrroles
  申请人：Hoffmann-La Roche Inc.

  公开号：US06228877B1

  公开（公告）日：2001-05-08

  Compounds of the formula 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, CO2R9, CH2OR10, CHO, CH2NR11R12, CON(R13)2, halogen, cyano, aryl, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, aralkyloxy, acylamino, monoalkylamino, dialkylamino, thio, alkyl, 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 or pharmaceutically acceptable 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.

  化合物的公式为其中R1和R1'分别独立地为烷基、芳基、烯基或炔基；R2和R2'分别独立地为氢、烷基、芳基烷基、烷氧基烷基、羟基烷基、卤代烷基、氨基烷基、单烷基氨基烷基、双烷基氨基烷基、酰胺基烷基、烷基磺酰胺基烷基、芳基磺酰胺基烷基、巯基烷基、烷硫基烷基、羧基烷基、烷氧羰基烷基、氨基羰基烷基、烷硫基或烷基亚磺酰基；R4、R5、R6、R7、R4'、R5'、R6'和R7'各自独立地为氢、CO2R9、CH2OR10、CHO、CH2NR11R12、CON(R13)2、卤素、氰基、芳基、烷基、羟基、烷氧基、芳氧基、卤代烷基、硝基、氨基、芳基氧基、酰胺基、单烷基氨基、双烷基氨基、硫基、烷基、烷基亚磺酰基、烷基磺酰基、芳基亚磺酰基、偶氮基、磷酸酯或膦酸酯，但至少有R4、R5、R6和R7中的一个和R4'、R5'、R6'和R7'中的一个不是氢，如果R6是甲氧基，则R5或R5'不是甲氧基；R8为烷基或芳基；R9为烷基或芳基；R10为氢、烷基或芳基；R11和R12独立地为氢、烷基、芳基、芳基烷基或酰基；R13为氢、烷基、芳基或芳基烷基；X和Y中的一个表示O，另一个表示O、S、(H,OH)或(H,H)；以及公式I的酸性化合物的药学上可接受的前药或与酸的公式I的碱性化合物的药学上可接受的盐是抗增殖剂，可用于癌症的治疗。
• Serotonergic alpha-oxoacetamides
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05192770A1

  公开（公告）日：1993-03-09

  .alpha.-Oxoacetamides of the formula R.sup.1 C(O)C(O)NR.sup.2 R.sup.3 in which R.sup.1 is optionally substituted phenyl, 1-indolyl, 2,3-dihydro-1-indolyl, 1-benzimidazolidinonyl, 3-benzofuranyl, 3-benzothiophenyl, 3-indolyl, and 1,2-alkano-3-indolyl; R.sup.2 is selected from: ##STR1## and R.sup.3 is selected from hydrogen or lower alkyl; and the pharmaceutically acceptable salts, individual isomers, mixtures of isomers, processes for preparation, compositions, and methods of use thereof.

  该文献描述了式为R.sup.1 C(O)C(O)NR.sup.2 R.sup.3的.alpha.-羰基乙酰胺，其中R.sup.1为可选取代的苯基、1-吲哚基、2,3-二氢-1-吲哚基、1-苯并咪唑啉基、3-苯并呋喃基、3-苯并硫杂苯基、3-吲哚基和1,2-烷基-3-吲哚基；R.sup.2选自：##STR1## R.sup.3选自氢或低碳基；以及其药学上可接受的盐、单体异构体、异构体混合物、制备过程、组合物和使用方法。
• Alpha-oxoacetamide derivatives
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0490263A1

  公开（公告）日：1992-06-17

  α-Oxoacetamides represented by Formula I wherein R¹ is selected from in which: the dashed line denotes an optional bond; X and Y are independently selected from hydrogen, halo, cyano, hydroxy, lower alkoxy, benzyloxy, lower alkyl, nitro, amino, aminocarbonyl, (lower alkyl)amino, di(lower alkyl)amino, and (lower alkanoyl)amino; Z is -O-, -S- or -N(R⁴)-; and R⁴ and R⁵ are independently selected from hydrogen or lower alkyl or (lower cycloalkyl) lower alkyl or are together -(CH₂)n- wherein n is an integer from 3 to 5; R² is selected from in which: p is 0 or 1; q is 1, 2 or 3; and R⁶ is C₁₋₇ alkyl; and R³ is selected from hydrogen or lower alkyl; their pharmaceutically acceptable salts, individual isomers and mixtures of isomers, processes for their preparation, compositions, and methods of use thereof.

  由式 I 代表的 α-氧代乙酰胺 其中 R¹ 选自 其中 虚线表示任选键； X和Y独立地选自氢、卤素、氰基、羟基、低级烷氧基、苄氧基、低级烷基、硝基、氨基、氨基羰基、(低级烷基)氨基、二(低级烷基)氨基和(低级烷酰基)氨基； Z 是-O-、-S-或-N(R⁴)-；以及 R⁴ 和 R⁵ 独立选自氢或低级烷基或（低级环烷基）低级烷基，或共同为-(CH₂)n-，其中 n 为 3 至 5 的整数； R² 选自 其中 p 是 0 或 1 q 是 1、2 或 3；以及 R⁶ 是 C₁₋₇ 烷基；以及 R³ 选自氢或低级烷基； 它们的药学上可接受的盐、单个异构体和异构体混合物、制备工艺、组合物及其使用方法。
• Discovery of potent and bioavailable GSK-3β inhibitors
  作者：Leyi Gong、Don Hirschfeld、Yun-Chou Tan、J. Heather Hogg、Gary Peltz、Zafrira Avnur、Pete Dunten

  DOI：10.1016/j.bmcl.2010.01.038

  日期：2010.3

  Here we report on the discovery of a series of maleimides which have high potency and good selectivity for GSK-3 beta. The incorporation of polar groups afforded compounds with good bioavailability. The most potent compound 34 has an IC(50) of 0.6 nM for GSK-3 beta, over 100-fold selectivity against a panel of other kinases, and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3 beta protein with 34 bound revealed the binding mode of the template and provided insights for future optimization opportunities. (C) 2010 Elsevier Ltd. All rights reserved.
• 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