methyl 3-amino-6-methoxy-1H-indole-2-carboxylate | 696649-63-5

• 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: methyl 3-amino-6-methoxy-1H-indole-2-carboxylate
• 英文别名: 3-amino-6-methoxy-1H-indole-2-carboxylic acid methyl ester
• CAS: 696649-63-5
• 化学式: C₁₁H₁₂N₂O₃
• mdl: MFCD03848203
• 分子量: 220.228
• InChiKey: RBSGNWXMWYXCGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  77.3
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-6-methoxy-1H-indole-2-carboxylate 、 N-氰基苯甲酰胺 以52%的产率得到N-(7-methoxy-4-oxo-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)benzamide
  参考文献：
  名称：

  Methyl 3-amino-1H-indole-2-carboxylates in the synthesis of 5H-pyrimido[5,4-b]indole derivatives

  摘要：

  Reactions of methyl 3-amino-1H-indole-2-carboxylates with aryl isocyanates, aryl isothiocyanates, and cyanamides led to the formation of 5H-pyrimido[5,4-b]indole derivatives. In the reaction with isocyanates formed 3-aryl-1H-pyrimido[5,4-b]indole-2,4(3H,5H)-diones that were involved into the alkylation at two nitrogen atoms. The reaction with isothiocyanates afforded 3-aryl-2-thioxo-2,3-dihydro-1H-pyrimido[5,4-b]indol-4(5H)-ones undergoing alkylation at the sulfur atom. The reactions with benzoylcyanamide and N-(4,6-dimethylpyrimidin-2-yl)cyanamide resulted in N-(4-oxo-4,5-dihydro-3H-pyrimido-[5,4-b]indol-2-yl)benzamides and 2-(4,6-dimethylpyrimidin-2-ylamino)-3H-pyrimido[5,4-b]indol-4(5H)-ones respectively.

  DOI：

  10.1134/s1070428009050224
• 作为产物：
  描述：

  6-甲氧基-1H-吲哚-2-羧酸甲酯 在 氯化重氮苯 、 sodium carbonate 、 盐酸 、 tin 作用下， 以 N,N-二甲基甲酰胺 、 水 、 异丙醇 为溶剂， 反应 32.0h， 以47%的产率得到methyl 3-amino-6-methoxy-1H-indole-2-carboxylate
  参考文献：
  名称：

  Methyl 3-amino-1H-indole-2-carboxylates in the synthesis of 5H-pyrimido[5,4-b]indole derivatives

  摘要：

  Reactions of methyl 3-amino-1H-indole-2-carboxylates with aryl isocyanates, aryl isothiocyanates, and cyanamides led to the formation of 5H-pyrimido[5,4-b]indole derivatives. In the reaction with isocyanates formed 3-aryl-1H-pyrimido[5,4-b]indole-2,4(3H,5H)-diones that were involved into the alkylation at two nitrogen atoms. The reaction with isothiocyanates afforded 3-aryl-2-thioxo-2,3-dihydro-1H-pyrimido[5,4-b]indol-4(5H)-ones undergoing alkylation at the sulfur atom. The reactions with benzoylcyanamide and N-(4,6-dimethylpyrimidin-2-yl)cyanamide resulted in N-(4-oxo-4,5-dihydro-3H-pyrimido-[5,4-b]indol-2-yl)benzamides and 2-(4,6-dimethylpyrimidin-2-ylamino)-3H-pyrimido[5,4-b]indol-4(5H)-ones respectively.

  DOI：

  10.1134/s1070428009050224

文献信息

• Design, synthesis and biological evaluation of 2-alkoxycarbonyl-3-anilinoindoles as a new class of potent inhibitors of tubulin polymerization
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Maria Kimatrai Salvador、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Giampietro Viola、Roberta Bortolozzi、Leentje Persoons、Jan Balzarini、Sandra Liekens、Dominique Schols

  DOI：10.1016/j.bioorg.2020.103665

  日期：2020.4

  A new class of inhibitors of tubulin polymerization based on the 2-alkoxycarbonyl-3-(3',4',5'-trimethoxyanilino)indole molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. The results presented show that the methoxy substitution and location on the indole nucleus plays an important role in inhibition of cell growth

  合成了基于2-烷氧基羰基-3-（3'，4'，5'-三甲氧基苯胺基）吲哚分子骨架的新型微管蛋白聚合抑制剂，并评估了其抗增殖活性，抑制微管蛋白聚合和细胞周期的作用。给出的结果表明，甲氧基取代和吲哚核上的位置在抑制细胞生长中起着重要作用，最优选的取代基是在C-6处。另外，期望在吲哚核的2-位具有小尺寸的酯官能团（甲氧基/乙氧基羰基）。同样，被甲基，乙基或正丙基烷基化或在N-1吲哚氮上具有苄基部分的类似物保留的活性与在母体N-1H类似物中观察到的活性相同。
• [EN] PYRROLOPYRIMIDINE DERIVATIVES AS MODULATORS OF MULTI-DRUG RESISTANCE (MDR)<br/>[FR] DERIVES PYRROLOPYRIMIDINIQUES CONVENANT COMME MODULATEURS DE LA MULTIRESISTANCE AUX MEDICAMENTS
  申请人：XENOVA LTD

  公开号：WO2004111052A1

  公开（公告）日：2004-12-23

  A compound which is a pyrrolopyrimidine of formula (I) wherein R1 is selected from H, Cl-C6 alkyl which is unsubstituted or substituted, (CH2)nAr1, (CH2)pNR4R5, halogen and (CH2)pX; R2 is CH2)pArl; R3 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)pZ and (CH2)pArl; P is an unsaturated 5, 6, or 7 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted; R4 and R5 which are the same or different are selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)nC3-C10 cycloalkyl, (CH2)nAr1 , and (CH2)nOR6, or R4 and R5 together with the nitrogen atom to which they are attached, form a saturated five or six membered nitrogen containing heterocyclic ring which may contain one extra heteroatom selected from 0, N and S and which is unsubstituted or substituted; R6 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, C3-C10 cycloalkyl, (CH2)nOC1-C6alkyl which is unsubstituted or substituted, (CH2)nO(CH2)nAr1 , (CH2)nCO2C1-C6,alkyl which is unsubstituted or substituted and (CH2)nAr1; X is selected from CN, azide, (CH2)nNHSO2R6 and (CH2)nNHCOR6; Z is selected from CN, CO2R6 and CONR4R5; Ar1 is the same or different when more than one is present within a given substituent group and is an unsaturated C6-C10 membered carbocylic group or an unsaturated 5-11 membered heterocycle, either of which is unsubstituted or substituted; p is an integer of 1 to 6; n is the same or different when more than one is present within a given substituent group and is 0 or an integer of 1 to 6; with the proviso that the pyrrolepyrimidine compound of formula (I) is other than 1-(4-benzyl-piperazin-1-yl)-9H-2,4,9-triaza-fluorene; and the pharmaceutically acceptable salts thereof, have activity as inhibitors of MRP (multidrug resistant protein) and may thus be used to modulate multidrug resistance, for instance in potentiating the cytotoxicity of a chemotherapeutic agent.

  化合物是一种公式为（I）的吡咯吡嘧啶，其中R1从H、未取代或取代的Cl-C6烷基、（CH2）nAr1、（CH2）pNR4R5、卤素和（CH2）pX中选择；R2为（CH2）pArl；R3从H、未取代或取代的Cl-C6烷基、（CH2）pZ和（CH2）pArl中选择；P为未取代或取代的不饱和5、6或7成员碳环或杂环；R4和R5相同或不同，从H、未取代或取代的Cl-C6烷基、（CH2）nC3-C10环烷基、（CH2）nAr1和（CH2）nOR6中选择，或者R4和R5与它们连接的氮原子一起形成饱和的含氮五元或六元杂环，可能含有一个额外的杂原子，选择自O、N和S，未取代或取代；R6从H、未取代或取代的Cl-C6烷基、C3-C10环烷基、（CH2）nOC1-C6烷基、未取代或取代的（CH2）nO（CH2）nAr1、未取代或取代的（CH2）nCO2C1-C6烷基和（CH2）nAr1中选择；X从CN、叠氮、（CH2）nNHSO2R6和（CH2）nNHCOR6中选择；Z从CN、CO2R6和CONR4R5中选择；Ar1当多个存在于给定的取代基组内时相同或不同，为未取代或取代的不饱和C6-C10成员碳环或未取代或取代的不饱和5-11成员杂环；p为1至6的整数；n当多个存在于给定的取代基组内时相同或不同，为0或1至6的整数；但是，公式（I）的吡咯吡嘧啶化合物不是1-（4-苄基哌嗪-1-基）-9H-2,4,9-三氮杂萘；其药学上可接受的盐具有作为MRP（多药耐药蛋白）抑制剂的活性，因此可用于调节多药耐药性，例如在增强化疗药物的细胞毒性方面。
• Methyl 3-amino-1H-indole-2-carboxylates in the synthesis of 5H-pyrimido[5,4-b]indole derivatives
  作者：A. S. Shestakov、Kh. S. Shikhaliev、O. E. Sidorenko、V. G. Kartsev、S. V. Simakov

  DOI：10.1134/s1070428009050224

  日期：2009.5

  Reactions of methyl 3-amino-1H-indole-2-carboxylates with aryl isocyanates, aryl isothiocyanates, and cyanamides led to the formation of 5H-pyrimido[5,4-b]indole derivatives. In the reaction with isocyanates formed 3-aryl-1H-pyrimido[5,4-b]indole-2,4(3H,5H)-diones that were involved into the alkylation at two nitrogen atoms. The reaction with isothiocyanates afforded 3-aryl-2-thioxo-2,3-dihydro-1H-pyrimido[5,4-b]indol-4(5H)-ones undergoing alkylation at the sulfur atom. The reactions with benzoylcyanamide and N-(4,6-dimethylpyrimidin-2-yl)cyanamide resulted in N-(4-oxo-4,5-dihydro-3H-pyrimido-[5,4-b]indol-2-yl)benzamides and 2-(4,6-dimethylpyrimidin-2-ylamino)-3H-pyrimido[5,4-b]indol-4(5H)-ones respectively.