methyl 4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylate | 909415-09-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylate
• 英文别名: Boc-Py-Py-Py-Py-OMe；Methyl 1-methyl-4-[[1-methyl-4-[[1-methyl-4-[[1-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrole-2-carbonyl]amino]pyrrole-2-carbonyl]amino]pyrrole-2-carbonyl]amino]pyrrole-2-carboxylate
• CAS: 909415-09-4
• 化学式: C₃₀H₃₆N₈O₇
• 分子量: 620.665
• InChiKey: MSVUAYBMQYSGKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  172
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 4-{[4-({4-[(4-Amino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carbonyl]-amino}-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biophysical and Biological Evaluation of a Series of Pyrrolobenzodiazepine−Poly(N-methylpyrrole) Conjugates

  摘要：

  A novel series of methyl ester-terminated C8-linked pyrrolobenzodiazepine (PBD)-poly(N-methylpyrrole) conjugates (50a-f) has been synthesized and their DNA interaction evaluated by thermal denaturation, DNA footprinting, and in vitro transcription stop assays. The synergistic effect of attaching a PBD unit to a polypyrrole fragment is illustrated by the large increase in DNA binding affinity (up to 50-fold) compared to the individual PBD and pyrrole components. 50a-f were found to bind mainly to identical DNA sequences but with apparent binding site widths increasing with molecular length and the majority of sites conforming to the consensus motif 5'-XGXW(z) (z = 3 +/- 1; W = A or T; X = any base but preferably a purine). They also provided robust sequence-selective blockade of transcription at sites corresponding approximately to their DNA footprints. 50a-f were shown to have good cellular/ nuclear penetration properties, and a degree of correlation between cytotoxicity and DNA-binding affinity was observed.

  DOI：

  10.1021/jm051199z
• 作为产物：
  描述：

  methyl 4-<<<4-<<(tert-butyloxy)carbonyl>amino>-1-methyl-pyrrol-2-yl>carbonyl>amino>-1-methyl-pyrrole-2-carboxylate 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 methyl 4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Biophysical and Biological Evaluation of a Series of Pyrrolobenzodiazepine−Poly(N-methylpyrrole) Conjugates

  摘要：

  A novel series of methyl ester-terminated C8-linked pyrrolobenzodiazepine (PBD)-poly(N-methylpyrrole) conjugates (50a-f) has been synthesized and their DNA interaction evaluated by thermal denaturation, DNA footprinting, and in vitro transcription stop assays. The synergistic effect of attaching a PBD unit to a polypyrrole fragment is illustrated by the large increase in DNA binding affinity (up to 50-fold) compared to the individual PBD and pyrrole components. 50a-f were found to bind mainly to identical DNA sequences but with apparent binding site widths increasing with molecular length and the majority of sites conforming to the consensus motif 5'-XGXW(z) (z = 3 +/- 1; W = A or T; X = any base but preferably a purine). They also provided robust sequence-selective blockade of transcription at sites corresponding approximately to their DNA footprints. 50a-f were shown to have good cellular/ nuclear penetration properties, and a degree of correlation between cytotoxicity and DNA-binding affinity was observed.

  DOI：

  10.1021/jm051199z

文献信息

• [EN] CONJUGATES FOR TREATING DISEASES<br/>[FR] CONJUGUÉS POUR LE TRAITEMENT DE MALADIES
  申请人：ENDOCYTE INC

  公开号：WO2016148674A1

  公开（公告）日：2016-09-22

  The present disclosure relates to pyrrolobenzodiazepine (PBD) prodrugs and conjugates thereof. The present disclosure also relates to pharmaceutical compositions of the conjugates described herein, methods of making and methods of using the same.

  本公开涉及吡咯苯并二氮杂环（PBD）前药及其结合物。本公开还涉及所述结合物的药物组合物，制备方法和使用方法。
• [EN] NOVEL BENZODIAZEPINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE BENZODIAZÉPINE
  申请人：IMMUNOGEN INC

  公开号：WO2010091150A1

  公开（公告）日：2010-08-12

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  该发明涉及具有抗增殖活性的新型苯二氮䓬啶衍生物，更具体地涉及具有式(I)和(II)的新型苯二氮䓬啶化合物，其中二氮䓬啶环(B)与杂环环(CD)融合，其中杂环环是双环的或式(III)的化合物，其中二氮䓬啶环(B)与杂环环(C)融合，其中杂环环是单环的。该发明提供了这些化合物的细胞毒性二聚体。该发明还提供了单体和二聚体的结合物。该发明进一步提供了使用该发明的化合物或结合物抑制异常细胞生长或治疗哺乳动物增殖性疾病的有效组合物和方法。该发明还涉及使用该发明的化合物或结合物进行体外、原位和体内诊断或治疗哺乳动物细胞或相关病理条件的方法。
• TARGET GENE TRANSCRIPTIONAL REPRESSION INHIBITOR THAT CAN BE DESIGNED IN A SEQUENCE-SPECIFIC MANNER, COMPOSITION CONTAINING SAME, AND USE THEREOF
  申请人：National University Corporation Chiba University

  公开号：US20210106612A1

  公开（公告）日：2021-04-15

  The present invention provides a target gene transcriptional repression inhibitor that can be designed in a sequence-specific manner, a composition containing the same, and use thereof. More specifically, the present invention provides a composition for use in inhibiting repression of gene expression by DNA methylation in a living subject, comprising pyrrole imidazole polyamide or a conjugate of pyrrole imidazole polyamide and a histone modifying enzyme inhibitor, wherein the pyrrole imidazole polyamide or the conjugate of pyrrole imidazole polyamide and a histone modifying enzyme inhibitor is designed so as to bind in a sequence-specific manner to a minor groove of promoter region DNA of the gene.

  本发明提供了一种可以以序列特异性方式设计的靶基因转录抑制剂，以及包含该抑制剂的组合物和其使用方法。更具体地，本发明提供了一种用于抑制DNA甲基化引起的基因表达抑制的组合物，包括吡咯咪唑聚酰胺或吡咯咪唑聚酰胺与组蛋白修饰酶抑制剂的结合物，其中吡咯咪唑聚酰胺或吡咯咪唑聚酰胺与组蛋白修饰酶抑制剂的结合物被设计成以序列特异性方式结合到基因启动子区域DNA的小沟。
• Alkyl 4- [4- (5-Oxo-2,3,5, 11A-Tetrahydo-5H-Pyrrolo [2, 1-C] [1,4] Benzodiazepine-8-Yloxy) -Butyrylamino]-1H-Pyrrole-2-Carboxylate Derivatives and Related Compounds For the Treatment of a Proliferative Disease
  申请人：Howard Philip Wilson

  公开号：US20080214525A1

  公开（公告）日：2008-09-04

  A compound of formula (I); or a salt or solvate thereof, wherein: the dotted line indicates the optional presence of a double bond between C2 and C3; R 2 is selected from —H, —OH, =0, ═CH 2 , —CN, —R, OR, halo, ═CH—R, O—SO 2 —R, CO 2 R and COR; R 7 is selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR′, nitro, Me 3 Sn and halo, where R and R′ are independently selected from optionally substituted C 1-7 alkyl, C 3-20 heterocyclyl and C 5-20 aryl groups; R 10 and R 11 either together form a double bond, or are selected from H and YR Y , where Y is selected from O, S and NH and R is H or C 1-7 alkyl or H and SO x M, where x is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; each X is independently a heteroarylene group; n is from 1 to 6; and R E is C 1-4 alkyl. The compound is useful for the treatment of proliferative diseases.

  化合物的公式（I）；或其盐或溶剂化物，其中：虚线表示C2和C3之间的双键是可选的；R2选择自-H，-OH，=0，═CH2，-CN，-R，OR，卤基，═CH-R，O-SO2-R，CO2R和COR；R7选择自H，R，OH，OR，SH，SR，NH2，NHR，NRR'，硝基，Me3Sn和卤基，其中R和R'独立选择自可选取代的C1-7烷基，C3-20杂环基和C5-20芳基基团；R10和R11要么一起形成双键，要么选择自H和YRY，其中Y选择自O，S和NH，R为H或C1-7烷基或H和SOxM，其中x为2或3，M为一价的药用可接受阳离子；每个X独立地是杂芳基基团；n为1至6；以及RE为C1-4烷基。该化合物可用于治疗增殖性疾病。
• Methods to identify therapeutic candidates
  申请人：Martin John Christopher

  公开号：US20070154906A1

  公开（公告）日：2007-07-05

  The invention provides systematic methods for identification of candidate compounds useful in treatment of conditions initiated or modulated by genetic expression. The methods of the invention permit efficient identification of candidates suitable for verification testing by in vitro and/or in vivo models.

  本发明提供了系统性方法，用于识别在遗传表达引起或调节的情况下有用于治疗的候选化合物。本发明的方法允许高效地识别适合通过体外和/或体内模型进行验证测试的候选物。