(E)-3-[(6aS)-4-hydroxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (E)-3-[(6aS)-4-hydroxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide
• 化学式: C₁₆H₁₇N₃O₃
• 分子量: 299.32
• InChiKey: SGQISVVTRYNHER-TZNOJPMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  95.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  安曲霉素 、 三氟乙酸 生成 (E)-3-[(6aS)-4-hydroxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide
  参考文献：
  名称：

  LEBER, JACK D.;HOOVER, JOHN R. E.;HOLDEN, KENNETH G.;JOHNSON, RANDALL K.;+, J. AMER. CHEM. SOC., 110,(1988) N 9, 2992-2993

  摘要：

  DOI：

文献信息

• Novel bis-pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates and a process for the preparation thereof
  申请人：Kamal Ahmed

  公开号：US20070259858A1

  公开（公告）日：2007-11-08

  The present invention provides novel bis-pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates of general formula V, useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of novel bis-pyrrolo[2,1 -c][1,4]benzodiazepine-anthraquinone conjugates of general formula V. wherein n=3, 4, or 5.

  本发明提供了一种新型的具有一般式V的双吡咯并[2,1-c][1,4]苯并二氮杂蒽醌共轭物，可作为潜在的抗人类癌细胞系的抗肿瘤药物。本发明还提供了一种制备新型双吡咯并[2,1-c][1,4]苯并二氮杂蒽醌共轭物的方法，其中n=3、4或5。
• [EN] PYRROLO [2,1-C][1, 4] BENZODIAZEPINE-GLYCOSIDE PRODRUGS USEFUL AS A SELECTIVE ANTI TUMOR AGENT<br/>[FR] PROMÉDICAMENTS PYRROLO [2,1-C][1,4] BENZODIAZÉPINE-GLYCOSIDES UTILES COMME AGENT ANTI-TUMORAL SÉLECTIF
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2009016647A1

  公开（公告）日：2009-02-05

  The present invention provides novel pyrrolo[2,1-c][1, 4]benzodiazepine- glycoside prodrug of general formula (1a-b), useful as selective anticancer agents. The present invention also provides a process for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepine-glycoside prodrugs of general formula (1a-b). This invention also provides activation of these produgs by E.coli β galactosidase and envisaged that these molecules are toxic to human cancer cell lines in the presence of the enzyme E.coli β -galactosidase. The prodrugs (1a and 1b) were also found to be toxic to human cancer HepG2 cells even in the absence of the E.coli β-galactosidase. The toxic effect of the molecules when activated was similar to that of the parent molecules (6a and 6b), respectively.

  本发明提供了一种新颖的通用公式（1a-b）的吡咯并[2,1-c][1,4]苯二氮䓬-糖苷前药，可用作选择性抗癌剂。本发明还提供了一种制备新型吡咯并[2,1-c][1,4]苯二氮䓬-糖苷前药的方法，其通用公式为（1a-b）。本发明还提供了通过大肠杆菌β-半乳糖苷酶激活这些前药，并预期这些分子在大肠杆菌β-半乳糖苷酶存在的情况下对人类癌细胞系具有毒性。这些前药（1a和1b）即使在没有大肠杆菌β-半乳糖苷酶的情况下，也被发现对人类癌细胞HepG2具有毒性。激活后分子的毒性效应与相应的母体分子（6a和6b）相似。
• [EN] PYRROLOBENZODIAZEPINE DERIVATIVES AS INHIBITORS OF NF-KAPPA B FOR THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] DÉRIVÉS DE PYRROLOBENZODIAZÉPINE UTILES EN TANT QU'INHIBITEURS DE NF-KAPPA B POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES
  申请人：KING S COLLEGE LONDON

  公开号：WO2020152462A1

  公开（公告）日：2020-07-30

  The invention relates to a compound of formula (I) or salts, solvates, stereoisomers, tautomers or combinations thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; and R1 and R2 are either (i) R1 and R2 together form a double bond; (ii) R1 is H and R2 is OH; or (iii) R1 is H and R2 is OC1-6 alkyl; Y is N-RB, S or O; Y1 is N or C-R8; q is o or 1; Het is where the carbonyl of the Het group is attached to the Y- & Y1-containing heterocyclic ring; Y2 is N-RB, S or O; Y3 is N or C-R10; Y4 is N-RB, S or O; Y5 is N or C-R10; Rx is H, RB, (CH2)m-ORB, halo, (CH2)m-NHRB and CO2RB; and each RB is independently selected from H, C1-6 alkyl and C1-6 haloalkyl. The invention also describes pharmaceutical compositions, and kits comprising compounds of formula (I) and their use for treating proliferative diseases such as multiple myeloma or chronic lymphocytic leukaemia and as NF-κΒ inhibitors.

  该发明涉及公式（I）的化合物或其盐、溶剂合物、立体异构体、互变异构体或它们的组合，其中虚线表示C1和C2或C2和C3之间的双键的可选存在；R1和R2要么（i）R1和R2一起形成双键；（ii）R1为H且R2为OH；或（iii）R1为H且R2为OC1-6烷基；Y为N-RB、S或O；Y1为N或C-R8；q为0或1；Het是Het基团的羰基连接到含有Y和Y1的杂环环上；Y2为N-RB、S或O；Y3为N或C-R10；Y4为N-RB、S或O；Y5为N或C-R10；Rx为H、RB、（CH2）m-ORB、卤素、（ ）m-NHRB和CO2RB；每个RB独立选择自H、C1-6烷基和C1-6卤代烷基。该发明还描述了制药组合物和包含公式（I）化合物的试剂盒，以及它们在治疗增殖性疾病如多发性骨髓瘤或慢性淋巴细胞白血病以及作为NF-κΒ抑制剂的用途。