anthramycin methyl ether | 5544-25-2

• 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: anthramycin methyl ether
• 英文别名: (E)-3-[(6R,6aS)-4-hydroxy-6-methoxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide
• CAS: 5544-25-2
• 化学式: C₁₇H₁₉N₃O₄
• 分子量: 329.356
• InChiKey: YRMCBQLZVBXOSJ-PCFSSPOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  anthramycin methyl ether 在 5'-d[TATAAGATTTTCTTATA]-3' 作用下， 反应 20.17h， 生成 (E)-3-(4-羟基-3-甲基-11-氧代吡咯并[5,1-c][1,4]苯并二氮杂卓-8-基)丙-2-烯酰胺
  参考文献：
  名称：

  Observation of the reversibility of a covalent pyrrolobenzodiazepine (PBD) DNA adduct by HPLC/MS and CD spectroscopy

  摘要：

  吡咯并苯并二氮杂卓（PBD）是一种序列选择性DNA小沟结合剂，能与鸟嘌呤共价结合，且据称对Pu-G-Pu序列（Pu = 嘌呤）有偏好。我们利用HPLC/MS和圆二色性（CD）方法首次证实了PBD分子与DNA之间形成的氨基键是可逆的。此外，我们还发现，虽然氨基键断裂的速度不取决于PBD分子对特定结合位点的序列偏好，但PBD-DNA加合物重新形成的速度却与此相关。我们还发现，PBD蒽霉素（2）似乎是一个例外，在从DNA断裂的过程中，其C环芳香化，由于C11位失去亲电性，因此无法重新结合。虽然此前有报告称，蒽霉素的C环芳香化发生在没有DNA且经过三氟乙酸（TFA）处理的情况下，但在这种情况下，不需要降低pH值，DNA本身似乎可以催化这一过程。

  DOI：

  10.1039/c0ob00762e
• 作为产物：
  描述：

  (E)-3-[(7S,8S)-8-hydroxy-13-methyl-2-oxo-10-phenyl-11-oxa-3,9-diazatetracyclo[7.6.1.03,7.012,16]hexadeca-1(16),4,12,14-tetraen-5-yl]prop-2-enamide 、 甲醇 、 盐酸 生成 anthramycin methyl ether
  参考文献：
  名称：

  PENA, MICHAEL R.;STILLE, J. K., J. AMER. CHEM. SOC., 111,(1989) N4, C. 5417-5424

  摘要：

  DOI：

文献信息

• Novel pyrrolo[2,1-C] [1,4] benzodiazepine compounds and processes for the preparation thereof
  申请人：Kamal Ahmed

  公开号：US20070082891A1

  公开（公告）日：2007-04-12

  The present invention provides novel pyrrolo [2,1-c][1,4]benzodiazepine compounds. This invention also provides a process for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepine compounds. These novel pyrrolo [2,1-c][1,4]benzodiazepine compounds are useful as antitumor agents. It also provides a process for the preparation of 7-methoxy-8-n-[4-(2-oxo-2H-4-chromenyl)piperazino]alkyl}-oxy-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one and 7-methoxy-8-n-[4-(7-alkoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]alkyl}-oxy-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]. benzodiazepine-5-one with aliphatic chain length variations for these compounds.

  本发明提供了新型吡咯并[2,1-c][1,4]苯二氮䓬化合物。本发明还提供了一种制备新型吡咯并[2,1-c][1,4]苯二氮䓬化合物的方法。这些新型吡咯并[2,1-c][1,4]苯二氮䓬化合物可用作抗肿瘤剂。还提供了一种制备7-甲氧基-8-n-[4-(2-氧代-2H-4-香豆素基)哌嗪基]烷基}-氧基-(11aS)-1,2,3,11a-5H-吡咯并[2,1-c][1,4]苯二氮䓬-5-酮和7-甲氧基-8-n-[4-(7-烷氧基-8-甲基-2-氧代-2H-4-香豆素基)哌嗪基]烷基}-氧基-(11aS)-1,2,3,11a-5H-吡咯并[2,1-c][1,4]苯二氮䓬-5-酮的方法，其中这些化合物具有不同的脂肪链长度变化。
• CARBAZOLE LINKED PYRROLO[2,1-C][1,4]BENZODIAZEFINE HYBRIDS AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF
  申请人：Kamal Ahmed

  公开号：US20130131336A1

  公开（公告）日：2013-05-23

  The present invention provides a compound of general formulae A useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formulae 6a-g, 10a-o, 14a-g and 18a-o.

  本发明提供了一种通式A的化合物，可作为潜在的抗人类癌细胞系抗肿瘤剂。本发明还提供了一种制备通式6a-g、10a-o、14a-g和18a-o的吡咯并[2,1-c][1,4]苯二氮杂环己烷杂合物的方法。
• 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。
• PYRROLO[2, 1-C][1, 4]BENZODIAZEPINE-GLYCOSIDE PRODRUG USEFUL AS A SELECTIVE ANTI TUMOR AGENT
  申请人：Ahmed Kamal

  公开号：US20090036657A1

  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 □-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型吡咯并[2,1-c][1,4]苯二氮杂环糖苷前药，其通用公式为1a-b，可作为选择性抗癌剂。本发明还提供了一种制备新型吡咯并[2,1-c][1,4]苯二氮杂环糖苷前药的方法，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。前药1a和1b甚至在没有大肠杆菌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。当被激活时，这些分子的毒性效果类似于相应的母体分子6a和6b。
• [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、（CH2）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。