(11S,11aS)-8-(2-benzyloxycarbonylethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester | 679005-40-4

• 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: (11S,11aS)-8-(2-benzyloxycarbonylethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester
• 英文别名: (11aS)-8-(2-benzyloxycarboxyethoxy)-7-methoxy-5-oxo-11-hydroxy-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2.1-c][1,4]benzodiazepine-10-carboxylic acid t-butyl ester；tert-butyl (6S,6aS)-6-hydroxy-2-methoxy-11-oxo-3-(3-oxo-3-phenylmethoxypropoxy)-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
• CAS: 679005-40-4
• 化学式: C₂₈H₃₄N₂O₈
• 分子量: 526.587
• InChiKey: ZPTNYGKHGHFVOX-FNZWTVRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (11S,11aS)-8-(2-benzyloxycarbonylethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以100%的产率得到(11S,11aS)-8-(2-carboxyethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  吡咯并[2,1-c] [1,4]苯并二氮杂（PBD）C8环胺共轭物的合成和生物学评估。

  摘要：

  我们报告了一系列新型的吡咯并[2,1-c] [1,4]苯二氮杂（PBD）类似物12-15的实例，这些类似物是从一种常见的功能化结构单元11制备的，可以方便地大规模合成并以光学纯净的形式进行合成形式。异吲哚啉类似物15是该系列中最具细胞毒性的药物，具有最高的DNA结合亲和力，并且在体内中空纤维测定中显示出显着的活性。

  DOI：

  10.1016/j.bmcl.2003.12.017
• 作为产物：
  描述：

  香草酸 在 sodium hydroxide 、 草酰氯 、 硝酸 、 对甲苯磺酸 、 二甲基亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 62.0h， 生成 (11S,11aS)-8-(2-benzyloxycarbonylethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  吡咯并[2,1-c] [1,4]苯并二氮杂（PBD）C8环胺共轭物的合成和生物学评估。

  摘要：

  我们报告了一系列新型的吡咯并[2,1-c] [1,4]苯二氮杂（PBD）类似物12-15的实例，这些类似物是从一种常见的功能化结构单元11制备的，可以方便地大规模合成并以光学纯净的形式进行合成形式。异吲哚啉类似物15是该系列中最具细胞毒性的药物，具有最高的DNA结合亲和力，并且在体内中空纤维测定中显示出显着的活性。

  DOI：

  10.1016/j.bmcl.2003.12.017

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。
• WO2007/39752
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Biophysical and Biological Evaluation of a Series of Pyrrolobenzodiazepine−Poly(<i>N</i>-methylpyrrole) Conjugates
  作者：Geoff Wells、Christopher R. H. Martin、Philip W. Howard、Zara A. Sands、Charles A. Laughton、Arnaud Tiberghien、Chi Kit Woo、Luke A. Masterson、Marissa J. Stephenson、John A. Hartley、Terence C. Jenkins、Steven D. Shnyder、Paul M. Loadman、Michael J. Waring、David E. Thurston

  DOI：10.1021/jm051199z

  日期：2006.9.1

  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.
• 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
• US8637664B2
  申请人：——

  公开号：US8637664B2

  公开（公告）日：2014-01-28