methyl 4-[[2-[4-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]butanoylamino]-1,3-thiazole-4-carbonyl]amino]-1-methylpyrrole-2-carboxylate | 934234-72-7

• 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: methyl 4-[[2-[4-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]butanoylamino]-1,3-thiazole-4-carbonyl]amino]-1-methylpyrrole-2-carboxylate
• CAS: 934234-72-7
• 化学式: C₂₈H₃₀N₆O₇S
• 分子量: 594.648
• InChiKey: BYKKVPAEFHCPOI-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  182
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  C₃₇H₄₃N₅O₁₂S 在 四氢吡咯 、 四(三苯基膦)钯 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以30%的产率得到methyl 4-[[2-[4-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]butanoylamino]-1,3-thiazole-4-carbonyl]amino]-1-methylpyrrole-2-carboxylate
  参考文献：
  名称：

  Novel C8-linked pyrrolobenzodiazepine (PBD)–heterocycle conjugates that recognize DNA sequences containing an inverted CCAAT box

  摘要：

  A series of novel DNA-interactive C8-linked pyrrolobenzodiazepine (PBD)-heterocyclepolyamide conjugates has been synthesised to explore structure/sequence-selectivity relationships. One conjugate (2d) has a greater selectivity and DNA binding affinity for inverted CCAAT sequences within the Topoisomerase II alpha promoter than the known C8-bis-pyrrole PBD conjugate GWL-78 (1b). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.054

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。
• US8637664B2
  申请人：——

  公开号：US8637664B2

  公开（公告）日：2014-01-28