XMD 8-85 | 1234479-76-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: XMD 8-85
• 英文别名: Erk5-IN-1；2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one
• CAS: 1234479-76-5
• 化学式: C₂₅H₂₉N₇O₂
• 分子量: 459.551
• InChiKey: DDTPGANIPBKTNU-UHFFFAOYSA-N

物化性质

• 熔点：
  >136°C (dec.)
• 沸点：
  699.3±65.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  XMD 8-85 在 三氟乙酸 作用下， 以 水 、 乙腈 为溶剂， 生成 2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5,11-dimethyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one trifluoroacetate
  参考文献：
  名称：

  [EN] PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS
  [FR] COMPOSÉS PYRIMIDO-DIAZÉPINONE D'ÉCHAFAUDAGE DE KINASE ET PROCÉDÉS DE TRAITEMENT DE TROUBLES

  摘要：

  公开号：

  WO2010080712A3
• 作为产物：
  描述：

  2-氯-11-甲基-5H-苯并[e]嘧啶[5,4-b][1,4]二氮杂卓-6(11H)-酮 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hydride 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 N,N-二甲基乙酰胺 、 叔丁醇 为溶剂， 生成 XMD 8-85
  参考文献：
  名称：

  Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a Potent and Selective Inhibitor of Big MAP Kinase 1

  摘要：

  Kinome-wide selectivity profiling of a collection of 2-amino-pyrido[2,3-d]pyrimidines followed by cellular structure activity relationship-guided optimization resulted in the identification of moderately potent and selective inhibitors of BMK1/ERK5 exemplified by 11, 18, and 21. For example, 11 possesses a dissociation constant (K-d) for BMK1 of 19 nM, a cellular IC50 for inhibiting epidermal growth factor induced BMK1 autophosphorylation of 0.19 +/- 0.04 mu M, and an Ambit KINOMEscan selectivity score (Ss) of 0.035. Inhibitors 18 and I 21 are also potent BMK1 inhibitors and possess favorable pharmacokinetic properties which enable their use as pharmacological probes of BMK1-dependent phenomena as well as starting points for further optimization efforts.

  DOI：

  10.1021/ml100304b

文献信息

• [EN] QUINOLINYL-PYRAZINE-CARBOXAMIDE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE QUINOLINYL-PYRAZINE-CARBOXAMIDE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2020132459A1

  公开（公告）日：2020-06-25

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinolinyl-pyrazine-carboxamide (or similar) structure which function as activators of the cholesterol biosynthesis pathway within cancer cells and/or immune cells, which function as activators of the cell cycle regulation pathway within cancer cells and/or immune cells, and which function as up-regulators of HMGCS1 protein expression within cancer cells and/or immune cells, and which function as effective therapeutic agents for treating, ameliorating, and preventing various forms of cancer and other inflammatory disease.

  这项发明属于药物化学领域。具体来说，该发明涉及一类新型小分子，其具有喹啉基-吡嗪-羧酰胺（或类似）结构，其在癌细胞和/或免疫细胞内作为胆固醇生物合成途径的激活剂，作为癌细胞和/或免疫细胞内细胞周期调控途径的激活剂，作为癌细胞和/或免疫细胞内HMGCS1蛋白表达的上调剂，以及作为治疗、改善和预防各种癌症和其他炎症性疾病的有效治疗剂。
• [EN] PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DCLK1/2-MEDIATED DISORDERS<br/>[FR] COMPOSÉS DE PYRIMIDO-DIAZÉPINONE KINASE DE TYPE ÉCHAFAUDAGE ET MÉTHODES DE TRAITEMENT DES TROUBLES INDUITS PAR LES DCLK1/2
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2018075608A1

  公开（公告）日：2018-04-26

  The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as doublecortin-like kinase (DCLK1) and doublecortin-like kinase 2 (DCLK2), which are members of serine/threonine-protein kinase family and Ca2+/calmodulin-dependent protein kinase class of enzymes, and the use of such compounds in the treatment of various diseases, disorders or conditions.

  本发明涉及使用嘧啶二氮杂环己二酮类化合物，这些化合物能够调节蛋白激酶，如双皮质素样激酶（DCLK1）和双皮质素样激酶2（DCLK2），它们是丝氨酸/苏氨酸蛋白激酶家族和钙/钙调蛋白激酶类酶的成员，并且涉及将这些化合物用于治疗各种疾病、疾病或病况。
• Synthesis and Structure–Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6<i>H</i>-benzo[<i>e</i>]pyrimido[5,4-<i>b</i>][1,4]diazepin-6-one Scaffold
  作者：Fleur M. Ferguson、Yan Liu、Wayne Harshbarger、Ling Huang、Jinhua Wang、Xianming Deng、Stephen J. Capuzzi、Eugene N. Muratov、Alexander Tropsha、Senthil Muthuswamy、Kenneth D. Westover、Nathanael S. Gray

  DOI：10.1021/acs.jmedchem.0c00596

  日期：2020.7.23

  inhibitor, DCLK1-IN-1, developed to aid the functional characterization of this important kinase. Here we describe the synthesis and structure–activity relationships of 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one DCLK1 inhibitors, resulting in the identification of DCLK1-IN-1.

  Doublecortin样激酶1（DCLK1）是一种丝氨酸/苏氨酸激酶，在胃肠道癌（包括食道癌，胃癌，结肠直肠癌和胰腺癌）中过表达。DCLK1还用作簇状细胞的标志物，簇状细胞可调节肠道中的II型免疫力。但是，DCLK1的基板和功能尚未得到充分研究。我们最近描述了第一个选择性DCLK1 / 2抑制剂DCLK1-IN-1，该抑制剂的开发是为了辅助这一重要激酶的功能表征。在这里，我们描述了5,11-二氢-6 H-苯并[ e ]嘧啶基[5,4- b ] [1,4]二氮杂-6-1 DCLK1抑制剂的合成与构效关系，从而鉴定了DCLK1-IN-1。
• [EN] DIAZEPANE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE DIAZÉPANE ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015117083A1

  公开（公告）日：2015-08-06

  The present invention provides compounds of any one of Formulae (I), (II-C) (e.g., Formula (II)), and (III), and pharmaceutically compositions thereof. Compounds of any one of Formulae (I), (II-C), and (III) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain- containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.

  本发明提供了任一式（I）、（II-C）（例如，式（II））和（III）的化合物，以及其药物组合物。据信，任一式（I）、（II-C）和（III）的化合物被认为是溴结构域和/或含溴结构域蛋白（例如，溴和额外末端（BET）蛋白）的结合物。还提供了使用这些化合物和药物组合物的方法、用途和试剂盒，用于抑制溴结构域和/或含溴结构域蛋白的活性（例如，增加活性），并用于治疗和/或预防与溴结构域或含溴结构域蛋白相关的疾病（例如，增殖性疾病、心血管疾病、病毒感染、纤维化疾病、代谢性疾病、内分泌疾病和放射性中毒）。这些化合物、药物组合物和试剂盒也适用于男性避孕。
• [EN] USES OF DIAZEPANE DERIVATIVES<br/>[FR] UTILISATIONS DES DÉRIVÉS DE DIAZÉPANE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015117087A1

  公开（公告）日：2015-08-06

  The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.

  本发明提供了式（II）的化合物（例如，式（I）的化合物），以及其药物组成物。式（II）的化合物被认为是溴域和/或含溴域蛋白（例如，溴和额外终端（BET）蛋白）的结合剂。还提供了使用这些化合物和药物组成物的方法、用途和工具包，用于抑制溴域和/或含溴域蛋白的活性（例如，增加的活性），并用于治疗和/或预防与溴域或含溴域蛋白相关的疾病（例如，增生性疾病、心血管疾病、病毒感染、纤维性疾病、代谢性疾病、内分泌疾病和放射性中毒）。这些化合物、药物组成物和工具包还可用于男性避孕。