3-(5-benzyloxy-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione | 287956-93-8

• 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-(5-benzyloxy-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione
• 英文别名: 3-bromo-4-(5-phenylmethoxy-1H-indol-3-yl)pyrrole-2,5-dione
• CAS: 287956-93-8
• 化学式: C₁₉H₁₃BrN₂O₃
• 分子量: 397.228
• InChiKey: HKNWCLFHWSSJKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(5-benzyloxy-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione 在 sodium azide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 3-(5-phenylmethoxy-1H-indol-3-yl)-4-[(tributyl-lambda5-phosphanylidene)amino]pyrrole-2,5-dione
  参考文献：
  名称：

  Pyrrolo[3,4-c]-β-carboline-diones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase

  摘要：

  Members of the structurally diverse family of beta-carbolines have previously been shown to exhibit a wide range of biological activities. A novel synthetic strategy for generation of beta-carbolines was developed, allowing imido-beta-carbolines to be created in three steps from known compounds. The compounds were screened for inhibition of platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation in Swiss 3T3 fibroblasts. A number of the newly synthesized beta-carbolines with moderate to potent inhibitory activity were revealed. The most active derivative, 2,3-dihydro-8,9-dimethoxy-5-(2-methylphenyl)-1H,6H-pyrrolo[3,4-c]pyrido[3,4-b]indole-1,3-dione 2ee, inhibited purified PDGF receptor kinase and PDGF-receptor autophosphorylation in intact cells with IC50 values of 0.4 and 2.6 mu M, respectively. Dione 2ee also inhibited PDGF-stimulated DNA synthesis in Swiss 3T3 fibroblasts with an IC50 of 3.2 mu M. The compound had no effect on Src or epidermal growth factor (EGF) receptor kinase activity and a six-seven-fold higher IC50 for inhibition of basic fibroblast growth factor (bFGF)-stimulated tyrosine phosphorylation or Kit/stem cell factor (SCF) receptor autophosphorylation, indicating a reasonable extent of kinase specificity. Thus, beta-carbolines present a new lead of tyrosine kinase inhibitors with the capacity to selectively interfere with PDGF receptor signal transduction and PDGF-dependent cell growth. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00140-9

文献信息

• Novel substituted [1,4] benzodioxino[2,3-e] isoindole derivatives, method for preparing and pharmaceutical compositions containing same
  申请人：Coudert Gerard

  公开号：US20060040930A1

  公开（公告）日：2006-02-23

  Compounds of formula (I): wherein: A is as defined in the description, Y represents a group selected from an oxygen atom and a methylene group, R 2 represents a hydrogen atom and in that case: R 3 represents a group selected from a hydrogen atom and the groups linear or branched (C 1 -C 6 )alkyl, aryl, aryl-(C 1 -C 6 )alkyl (in which the alkyl moiety is linear or branched) and SO 2 CF 3 , or R 2 and R 3 form a bond, R 1 represents a group selected from a hydrogen atom and the groups linear or branched (C 1 -C 6 )alkyl, aryl and aryl-(C 1 -C 6 )alkyl (in which the alkyl moiety is linear or branched) or a linear or branched (C 1 -C 6 )alkylene chain, Z 1 and Z 2 each represent a hydrogen atom or Z 1 and Z 2 , together with the carbon atoms carrying them, form a phenyl group. Medicaments.

  式(I)的化合物：其中：A如描述中定义，Y代表从氧原子和亚甲基组中选择的一个基团，R2代表氢原子，此时：R3代表从氢原子和线性或支链的(C1-C6)烷基，芳基，芳基-(C1-C6)烷基（其中烷基基团是线性或支链的）和SO2CF3中选择的一个基团，或者R2和R3形成键，R1代表从氢原子和线性或支链的(C1-C6)烷基，芳基和芳基-(C1-C6)烷基（其中烷基基团是线性或支链的）或线性或支链的(C1-C6)烷基链中选择的一个基团，Z1和Z2各自代表氢原子或Z1和Z2与携带它们的碳原子一起形成苯基。药物。
• Novel 5-azaindolocarbazoles as cytotoxic agents and Chk1 inhibitors
  作者：Myriam Lefoix、Gérard Coudert、Sylvain Routier、Bruno Pfeiffer、Daniel-Henri Caignard、John Hickman、Alain Pierré、Roy M. Golsteyn、Stéphane Léonce、Céline Bossard、Jean-Yves Mérour

  DOI：10.1016/j.bmc.2008.02.086

  日期：2008.5

  nitrogen atom of the maleimide were prepared, as well as derivatives with glucopyranosyl substituent on the nitrogen atom of the indole moiety. The cytotoxicity of these new compounds was evaluated on two cell lines (L1210, HT29). Several compounds showed cytotoxicity in the sub-micromolar range. Among the most cytototoxic was the 1,3-dioxolo[4,5-b]-6-(2-dimethylaminoethyl)-1H-pyrido[3',4':4,5]pyrrolo[3,2-i]pyr

  我们在这里描述了一种新的5-氮杂吲哚并咔唑的有效合成方法，该化合物设计用于具有细胞毒性和抑制Chk1的特性。讨论了“对称”和“不对称”结构的综合。关于具有吲哚部分和5-氮杂吲哚部分的不对称5-氮杂吲哚并咔唑衍生物，使用两个非常有效的关键步骤实现了合成。第一个是与3-三甲基锡烷基-5-氮杂吲哚衍生物进行的Stille反应，第二个是导致所提出的多环结构的光化学步骤。进行了各种药物调节以研究结构-活性关系（SAR）。几个取代基（如OBn，OH和亚甲二氧基）已成功引入5-氮杂吲哚并咔唑的吲哚部分。制备了在马来酰亚胺的氮原子上具有或没有取代基的化合物，以及在吲哚部分的氮原子上具有吡喃葡萄糖基取代基的衍生物。在两种细胞系（L1210，HT29）上评估了这些新化合物的细胞毒性。几种化合物在亚微摩尔范围内显示出细胞毒性。其中最具细胞毒性的是1,3-二氧杂环戊并[4,5-b] -6-（2-二甲基氨基乙基）-1H-吡啶并[3'，4'：4
• NOUVEAUX DERIVES DE 1,4 BENZODIOXINO 2,3-e ISOINDOLE SUBSTITUES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：Les Laboratoires Servier

  公开号：EP1587810A1

  公开（公告）日：2005-10-26
• US7202255B2
  申请人：——

  公开号：US7202255B2

  公开（公告）日：2007-04-10
• [EN] NOVEL SUBSTITUTED[1,4]BENZODIOXINO[2,3-E]ISOINDOLE DERIVATIVES, METHOD FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] NOUVEAUX DERIVES DE [1,4]BENZODIOXINO[2,3-e]ISOINDOLE SUBSTITUES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：SERVIER LAB

  公开号：WO2004037831A1

  公开（公告）日：2004-05-06

  Composés de formule (I) dans laquelle : A est tel que définis dans la description, Y représente un groupement choisi parmi atome d'oxygène ou groupement méthylène, R2 représente un atome d'hydrogène, et dans ce cas R3 représente un groupement choisi parmi atome d'hydrogène, groupement alkyle (C1-C6) linéaire ou ramifié, aryle, arylalkyle (C1-C6) linéaire ou ramifié, ou SO2CF3, ou bien R2 et R3 forment une liaison, R1 représente un groupement choisi parmi atome d'hydrogène, groupement alkyle (C1-C6) linéaire ou ramifié, aryle, arylalkyle (C1-C6) linéaire ou ramifié, ou une chaîne alkylène (C1-C6) linéaire ou ramifié, Zl et Z2 représentent chacun un atome d'hydrogène ou, Zl et Z2 forment ensemble, avec les atomes de carbone qui les portent, un groupement phényle, Médicaments.