(S)-2-(3-aminophenyl)-7-methoxy-8-(5-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)pentyloxy)-1H-pyrrolo[2,1-c][1,4]benzodiazepin-5(11aH)-one | 1222490-50-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-2-(3-aminophenyl)-7-methoxy-8-(5-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)pentyloxy)-1H-pyrrolo[2,1-c][1,4]benzodiazepin-5(11aH)-one
• 英文别名: (6aS)-3-[5-[[(6aS)-8-(3-aminophenyl)-2-methoxy-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]pentoxy]-2-methoxy-8-[4-(4-methylpiperazin-1-yl)phenyl]-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-11-one
• CAS: 1222490-50-7
• 化学式: C₄₈H₅₁N₇O₆
• 分子量: 821.976
• InChiKey: GTWUIHNGUAVXRQ-UWXQCODUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  61
• 可旋转键数：
  13
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  11

文献信息

• [EN] UNSYMMETRICAL PYRROLOBENZODIAZEPINE-DIMERS FOR TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] DIMÈRES DE PYRROLOBENZODIAZÉPINES ASYMÉTRIQUES UTILISÉS DANS LE TRAITEMENT DES MALADIES PROLIFÉRATIVES
  申请人：SPIROGEN LTD

  公开号：WO2010043880A1

  公开（公告）日：2010-04-22

  Claimed are unsymmetrical Pyrrolobenzodiazepine-dimers (PBD-dimers) of formula (I), that are unsymmetrical due at least to the values that the variables R12 and R2 represent. Formula (I), wherein: R2 is of formula (II), where A is a C5-7 aryl group, X is selected from the group comprising: OH, SH, CO2H, COH, N=C=O, NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl, and (OC2H4)mOCH3, where m is 1 to 3, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and -Z-(CH2)n-, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is -CH=CH-, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene. The other variables are as defined in the claims. The compounds are useful for the treatment of proliferative diseases.

  所述为式(I)的不对称吡咯并苯并二氮杂卓二聚体(PBD-二聚体)，其不对称性至少由于变量R12和R2所代表的值。式(I)中：R2为式(II)，其中A为C5-7芳基，X选自包括OH、SH、CO2H、COH、N=C=O、NHRN的组，其中RN选自包括H和C1-4烷基的组，以及(OC2H4)mOCH3，其中m为1至3，且任选地：(i) Q1为单键，Q2选自单键和-Z-(CH2)n-，其中Z选自单键、O、S和NH，n为1至3；或(ii) Q1为-CH=CH-，Q2为单键；R12为C5-10芳基，任选地被一个或多个选自包括卤素、硝基、氰基、醚、C1-7烷基、C3-7杂环烷基和双氧-C1-3亚烷基的组的取代基取代。其他变量如权利要求中所定义。这些化合物可用于增殖性疾病的治疗。
• UNSYMMETRICAL PYRROLOBENZODIAZEPINE-DIMERS FOR TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Howard Philip Wilson

  公开号：US20110196148A1

  公开（公告）日：2011-08-11

  Claimed are unsymmetrical Pyrrolobenzodiazepine-dimers (PBD-dimers) of formula (I), that are unsymmetrical due at least to the values that the variables R 12 and R 2 represent. Formula (I), wherein: R 2 is of formula (II), where A is a C 5-7 aryl group, X is selected from the group comprising: OH, SH, CO 2 H, COH, N═C═O, NHR N , wherein R N is selected from the group comprising H and C 1-4 alkyl, and (OC 2 H 4 ) m OCH 3 , where m is 1 to 3, and either: (i) Q 1 is a single bond, and Q 2 is selected from a single bond and —Z—(CH 2 ) m —, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q 1 is —CH═CH—, and Q 2 is a single bond; R 12 is a C 5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C 1-7 alkyl, C 3-7 heterocyclyl and bis-oxy-C 1-3 alkylene. The other variables are as defined in the claims. The compounds are useful for the treatment of proliferative diseases.

  所述的是公式（I）的非对称吡咯并苯并二氮杂环双聚物（PBD-二聚体），其非对称性至少由变量R12和R2所代表的值决定。公式（I）中：R2为公式（II）的结构，其中A为C5-7芳基基团，X选自包括：OH、SH、CO2H、COH、N═C═O、NHRN的群，其中RN选自包括H和C1-4烷基的群，以及（OC2H4）mOCH3，其中m为1至3，并且要么：（i）Q1为单键，Q2选自单键和—Z—（CH2）m—，其中Z选自单键、O、S和NH，n为1至3；要么（ii）Q1为—CH═CH—，Q2为单键；R12为C5-10芳基基团，可选择地被一个或多个取代基所取代，所述取代基选自卤、硝基、氰基、醚、C1-7烷基、C3-7杂环基和双氧-C1-3烷基。其他变量如权利要求所定义。所述化合物用于治疗增殖性疾病。
• TARGETED PYRROLOBENZODIAZAPINE CONJUGATES
  申请人：Howard Philip Wilson

  公开号：US20130028919A1

  公开（公告）日：2013-01-31

  Provided are Conjugate comprising PBDs conjugated to a targeting agent and methods of using such PBDs.

  提供了一种包含PBDs与靶向剂结合的共轭物，并提供了使用这种PBDs的方法。
• PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
  申请人：MEDIMMUNE LIMITED

  公开号：US20160250344A1

  公开（公告）日：2016-09-01

  A compound which is selected from A: and salts and solvates thereof.

  从A中选择的化合物及其盐和溶剂化物。
• PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
  申请人：MEDIMMUNE LIMITED

  公开号：US20160263242A1

  公开（公告）日：2016-09-15

  Conjugates of specific PBD dimers with an antibody that that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.

  特定PBD二聚体的共轭物与结合CD19的抗体，该抗体包括具有以下任一序列的VH结构域SEQ ID NOs. 1, 2, 3, 4, 5或6，可选地进一步包括具有以下任一序列的VL结构域SEQ ID NOs. 7, 8, 9, 10, 11或12。