[8-chloro-3-(4-chloro-phenyl)-7-iodo-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-(4-chloro-phenyl)-acetic acid | 528849-36-7

• 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: [8-chloro-3-(4-chloro-phenyl)-7-iodo-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-(4-chloro-phenyl)-acetic acid
• 英文别名: 2-[8-Chloro-3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-2-(4-chlorophenyl)acetic acid
• CAS: 528849-36-7
• 化学式: C₂₃H₁₄Cl₃IN₂O₄
• 分子量: 615.639
• InChiKey: QOQUWWZUQBEUTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

文献信息

• [EN] SUBSTITUTED 1,4-BENZODIAZEPINES AND USES THEREOF FOR THE TREATMENT OF CANCER<br/>[FR] 1,4-BENZODIAZEPINES SUBSTITUEES ET LEURS UTILISATIONS POUR LE TRAITEMENT DU CANCER
  申请人：DIMENSIONAL PHARM INC

  公开号：WO2003041715A1

  公开（公告）日：2003-05-22

  The present invention is directed to novel 1,4-benzodiazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: X and Y are independently -C(O)-, CH2- or -C(S)-; R?1, R2, R3, R4, R7, R8, Rb, Rc, Rd¿ and M are defined herein, R5 is hydrogen, alkyl cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaryl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R6 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R9 is cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkyl(alkyl), aralkyl or heteroarylalkyl, each of which is optionally substituted; and R10 is -(CH¿2?)n-CO2R?b¿, -(CH¿2?)m-CO2M, -(CH2)i-OH or -(CH2)j-CONR?cRd¿ n is 0-8, m is 0-8, i is 1-8 and j is 0-8.

  本发明涉及新型1,4-苯二氮平类化合物、其制药组合物以及作为HDM2-p53相互作用抑制剂的用途。化合物具有式(I)或其溶剂化物、水合物或药学上可接受的盐；其中：X和Y独立地为-C（O）-、CH2-或-C（S）-；R?1、R2、R3、R4、R7、R8、Rb、Rc、Rd¿和M的定义如本文所述，R5为氢、烷基环烷基、可选取代芳基、可选取代杂环芳基、可选取代芳基烷基、可选取代杂环芳基、羧基烷基、烷氧基羧酸酯、烷氧基羧酸酯烷基、氨基甲酰基、氨基甲酰基烷基、烷基氨基甲酰基或烷基氨基甲酰基烷基；R6为环烷基、芳基、杂环芳基、环烷基烷基、芳基烷基、杂环芳基烷基或饱和或部分不饱和杂环，每个都可以取代；R9为环烷基、芳基、杂环芳基、饱和或部分不饱和杂环、环烷基（烷基）、芳基烷基或杂环芳基烷基，每个都可以取代；R10为-( )n-CO2R?b¿、-( )m-CO2M、-( )i-OH或-( )j-CONR?cRd¿，其中n为0-8，m为0-8，i为1-8，j为0-8。
• Substituted 1,4-benzodiazepines and uses thereof
  申请人：——

  公开号：US20030109518A1

  公开（公告）日：2003-06-12

  The present invention is directed to novel 1,4-benzodiazepines, 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: X and Y are independently —C(O)—, —CH 2 — or —C(S)—; R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R b , R c , R d and M are defined herein; R 5 is hydrogen, alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R 6 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R 9 is cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkyl(alkyl), aralkyl or heteroarylalkyl, each of which is optionally substituted; and R 10 is —(CH 2 ) n —CO 2 R b , —(CH 2 ) m —CO 2 M, —(CH 2 ) i —OH or —(CH 2 ) j —CONR c R d n is 0-8, m is 0-8, i is 1-8 and j is 0-8.

  本发明涉及新型1,4-苯二氮平化合物，其药物组合物以及作为HDM2-p53相互作用抑制剂的用途。化合物具有公式I：1或其溶剂化物，水合物或药学上可接受的盐；其中：X和Y独立地为—C（O）—，—CH2—或—C（S）—；R1、R2、R3、R4、R7、R8、Rb、Rc、Rd和M在此定义；R5为氢，烷基，环烷基，可选取代芳基，可选取代杂环芳基，可选取代芳基烷基，可选取代杂环芳基烷基，羧基烷基，烷氧羰基，烷氧羰基烷基，氨基羰基，氨基羰基烷基，烷基氨基羰基或烷基氨基羰基烷基；R6为环烷基，芳基，杂环芳基，环烷基烷基，芳基烷基，杂环芳基烷基或饱和或部分不饱和杂环，每个都可以选择性地取代；R9为环烷基，芳基，杂环芳基，饱和或部分不饱和杂环，环烷基（烷基），芳基烷基或杂环芳基烷基，每个都可以选择性地取代；R10为—（ ）n—CO2Rb，—（ ）m—CO2M，—（ ）i—OH或—（ ）j—CONRcRd，其中n为0-8，m为0-8，i为1-8，j为0-8。
• HDM2-inhibitor complexes and uses thereof
  申请人：——

  公开号：US20040197893A1

  公开（公告）日：2004-10-07

  The present invention includes crystallized HDM2 peptides as well as descriptions of the X-ray diffraction patterns of the crystals. The diffraction patterns allow the three dimensional structure of HDM2 to be determined at atomic resolution so that ligand binding sites on HDM2 can be identified and the interactions of ligands with HDM2 amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MDM2 and HDM2 oncoproteins.

  本发明包括 HDM2 肽的结晶以及晶体的 X 射线衍射图样说明。通过衍射图样可以确定 HDM2 的原子分辨率三维结构，从而确定 HDM2 上的配体结合位点，并建立配体与 HDM2 氨基酸残基相互作用的模型。利用这种图谱制备的模型可以设计出具有活性的配体，其中包括但不限于具有抑制 MDM2 和 HDM2 肿瘤蛋白功能的配体。
• SUBSTITUTED 1,4-BENZODIAZEPINES AND USES THEREOF FOR THE TREATMENT OF CANCER
  申请人：3-DIMENSIONAL PHARMACEUTICALS, INC.

  公开号：EP1443937A1

  公开（公告）日：2004-08-11
• HDM2-INHIBITOR COMPLEXES AND USES THEREOF
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1743040A2

  公开（公告）日：2007-01-17