methyl 4-({4-[(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-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxylate | 909415-11-8

• 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-({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-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carboxylate
• 英文别名: Methyl 4-({4-[(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-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carboxylate；methyl 1-methyl-4-[[1-methyl-4-[[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-carbonyl]amino]pyrrole-2-carbonyl]amino]pyrrole-2-carboxylate
• CAS: 909415-11-8
• 化学式: C₄₂H₄₈N₁₂O₉
• 分子量: 864.918
• InChiKey: DVJICEPLZHDVSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  63
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  240
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 4-({4-[(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-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
  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 1-methyl-4-(1-methyl-4-aminopyrrole-2-carboxamido)-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 66.5h， 生成 methyl 4-({4-[(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-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

• 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。
• 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：US08637664B2

  公开（公告）日：2014-01-28

  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; R2 is selected from —H, —OH, =0, ═CH2, —CN, —R, OR, halo, ═CH—R, O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo, where R and R′ are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R10 and R11 either together form a double bond, or are selected from H and YRY, where Y is selected from O, S and NH and R is H or C1-7 alkyl or H and SOxM, 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 RE is C1-4 alkyl. The compound is useful for the treatment of proliferative diseases.

  化合物的式子（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从—H，—OH，=0，═CH2，—CN，—R，OR，卤素，═CH—R，O—SO2—R，CO2R和COR中选择；R7从H，R，OH，OR，SH，SR，NH2，NHR，NRR'，硝基，Me3Sn和卤素中选择，其中R和R'分别从选择性取代的C1-7烷基，C3-20杂环基和C5-20芳基中独立选择；R10和R11要么一起形成双键，要么从H和YRY中选择，其中Y从O，S和NH中选择，R是H或C1-7烷基或H和SOxM，其中x为2或3，M是单价的药用可接受阳离子；每个X都是独立的杂芳基基团；n为1到6；RE是C1-4烷基。该化合物用于治疗增生性疾病。
• WO2007/39752
  申请人：——

  公开号：——

  公开（公告）日：——
• ALKYL 4- [4- (5-OXO-2, 3, 5, 11A-TETRAHYD0-5H-PYRR0L0 [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：Spirogen Limited

  公开号：EP1931671B1

  公开（公告）日：2009-04-08