4-(4-chloro-2-hydroxybenzyl)-3-(4-chlorophenyl)-7-iodo-1-[2-(2-methoxy-ethoxy)ethyl]-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

• 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: 4-(4-chloro-2-hydroxybenzyl)-3-(4-chlorophenyl)-7-iodo-1-[2-(2-methoxy-ethoxy)ethyl]-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
• 英文别名: 4-(4-chloro-2-hydroxybenzyl)-3-(4-chlorophenyl)-7-iodo-1-[2-(2-methoxyethoxy)ethyl]-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione；4-[(4-chloro-2-hydroxyphenyl)methyl]-3-(4-chlorophenyl)-7-iodo-1-[2-(2-methoxyethoxy)ethyl]-3H-1,4-benzodiazepine-2,5-dione
• 化学式: C₂₇H₂₅Cl₂IN₂O₅
• 分子量: 655.316
• InChiKey: ZMHHWPQWCVSKMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  79.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 potassium tert-butylate 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 4-(4-chloro-2-hydroxybenzyl)-3-(4-chlorophenyl)-7-iodo-1-[2-(2-methoxy-ethoxy)ethyl]-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
  参考文献：
  名称：

  新型1,4-苯并二氮杂-2,5-二酮类化合物作为Hdm2拮抗剂，具有改善的细胞活性。

  摘要：

  p53-Hdm2蛋白质-蛋白质相互作用的破坏诱导细胞生长停滞和凋亡。我们已经确定了1,4-苯并二氮杂-2,5-二酮支架是通过与Hdm2蛋白结合来抑制这种相互作用的合适模板。已经制备了具有增强的效力，溶解性和基于细胞的活性的几种化合物。

  DOI：

  10.1016/j.bmcl.2006.04.009

文献信息

• Substituted 1,4-diazepines and uses thereof
  申请人：——

  公开号：US20040220179A1

  公开（公告）日：2004-11-04

  The present invention is directed to novel 1,4-diazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I: 1 or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: R 1 , R 2 , R 9 , R 10 , R a , R d and M are defined herein; X is a bivalent radical of: an alkane, a cycloalkane, an optionally-substituted arene, an optionally-substituted heteroarene, an optionally-substituted arylalkane or an optionally-substituted heteroarylalkane; and R 3 is —CO 2 R d , —CO 2 M, —OH, —NHR d , —SO 2 R d , —NHCONHR d , optionally-substituted amidino or optionally-substituted guanidino; or R 3 —X— is hydrogen or an electron pair; R 4 is oxygen or —NR 9 R 10 ; R 5 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; and R 6 , R 7 and R 8 are independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkylalkyl, aralkyl or heteroarylalkyl, each of which is optionally substituted; or R 6 and R 7 , together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted 1 to 3 times with R a .

  本发明涉及新型1,4-二氮杂环烷化合物，其药物组成物，以及其作为HDM2-p53相互作用抑制剂的用途。化合物具有以下结构式I：1或其溶剂化合物、水合物或药用可接受盐；其中：R1、R2、R9、R10、Ra、Rd和M在此处定义；X是以下结构的双价基团：烷烃、环烷烃、可选取代芳烃、可选取代杂芳烃、可选取代芳基烷烃或可选取代杂芳基烷烃；而R3为—CO2Rd、—CO2M、—OH、—NHRd、—SO2Rd、—NHCONHRd、可选取代酰胺基或可选取代胍基；或者R3—X—为氢或电子对；R4为氧或—NR9R10；R5为环烷基、芳基、杂芳基、环烷基烷基、芳基烷基、杂芳基烷基，或饱和或部分不饱和的杂环，每种均可选取代；而R6、R7和R8独立地为氢、烷基、环烷基、芳基、杂芳基、饱和或部分不饱和的杂环、环烷基烷基、芳基烷基、杂芳基烷基，每种均可选取代；或者R6和R7，与它们相连的碳原子共同形成一个3至7成员的碳环，可选取代1至3次以Ra。
• Combinational therapy involving a small molecule inhibitor of the MDM2: p53 interaction
  申请人：Lu Tianbao

  公开号：US20050227932A1

  公开（公告）日：2005-10-13

  The present invention is directed to a combinational therapy for treating cancer or other cell proliferative diseases. Such a therapy combines the use of radiation therapy or chemotherapy with the use of a small molecule inhibitor of the MDM2: p53 interaction.

  本发明针对治疗癌症或其他细胞增殖性疾病提供了一种联合治疗方案。这种治疗方案将放射治疗或化疗与使用MDM2：p53相互作用的小分子抑制剂相结合。
• Combinational therapy involving a small molecule inhibitor of the MDM2: P53 interaction
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1712235A2

  公开（公告）日：2006-10-18

  The present invention is directed to a combinational therapy for treating cancer or other cell proliferative diseases. Such a therapy combines the use of radiation therapy or chemotherapy with the use of a small molecule inhibitor of the MDM2: p53 interaction.

  本发明涉及一种治疗癌症或其他细胞增殖性疾病的组合疗法。这种疗法将放疗或化疗与 MDM2：p53 相互作用的小分子抑制剂结合使用。
• US7115598B2
  申请人：——

  公开号：US7115598B2

  公开（公告）日：2006-10-03
• [EN] SUBSTITUTED 1,4-DIAZEPINES AND USES THEREOF<br/>[FR] 1,4-DIAZEPINES SUBSTITUEES ET LEURS UTILISATIONS
  申请人：DIMENSIONAL PHARM INC

  公开号：WO2004096134A2

  公开（公告）日：2004-11-11

  The present invention is directed to novel 1,4-diazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I as defined herein, with R 1 to R 8 and X as defined herein or a solvate, hydrate or pharmaceutically acceptable salt thereof.