2-(3-chloroquinoxalin-2-yl)propanedinitrile | 10176-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(3-chloroquinoxalin-2-yl)propanedinitrile
• 英文别名: 2-(3-chloroquinoxalin-2-yl)malononitrile；(3-Chloroquinoxalin-2-yl)malononitrile
• CAS: 10176-25-7
• 化学式: C₁₁H₅ClN₄
• mdl: MFCD03952862
• 分子量: 228.641
• InChiKey: HQAKIUSGLUOLHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  382.0±37.0 °C(Predicted)
• 密度：
  1.439±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-chloroquinoxalin-2-yl)propanedinitrile 在 硫酸 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.5h， 生成 2-amino-1-(o-tolyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242
• 作为产物：
  描述：

  2,3-二氯喹喔啉 、 丙二腈 在 sodium hydride 作用下， 以 乙二醇二甲醚 、 mineral oil 为溶剂， 反应 1.33h， 以57%的产率得到2-(3-chloroquinoxalin-2-yl)propanedinitrile
  参考文献：
  名称：

  发现口服生物可利用的选择性 PKMYT1 抑制剂 RP-6306

  摘要：

  PKMYT1 是 CDK1 磷酸化的调节剂，由于其与CCNE1扩增建立的合成致死关系，因此成为治疗某些类型 DNA 损伤反应癌症的引人注目的治疗靶点。迄今为止，尚未报道该激酶的选择性抑制剂可用于研究 PKMYT1 的药理作用。为了满足这一需求，化合物1被确定为弱 PKMYT1 抑制剂。引入二甲基苯酚可增加对 PKMYT1 的效力。人们发现这些二甲基苯酚类似物以阻转异构体的形式存在，可以将其分离并分析为单一对映异构体。基于结构的药物设计能够优化基于细胞的效力。ADME 特性的并行优化导致鉴定出 PKMYT1 的有效且选择性抑制剂。RP-6306在多种临床前异种移植模型中抑制CCNE1扩增的肿瘤细胞生长。一流的临床候选药物RP-6306目前正在评估用于治疗各种实体瘤的 1 期临床试验。

  DOI：

  10.1021/acs.jmedchem.2c00552

文献信息

• 2-Amino-1-phenyl-pyrrolo[3,2-b]quinoxaline-3-carboxamide derivates
  申请人：Universität Zürich

  公开号：EP2924039A1

  公开（公告）日：2015-09-30

  The invention relates to compound characterized by a general formula (1), wherein n of R1n is 0, 1, 2, 3 or 4, in particular n of R1n is 0 or 1, and each R1 independently from any other R1 is C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy, and DA is a Donor-Acceptor group. The invention relates further to a compound or a pharmaceutical preparation for use in a method for treatment of cancer or intraocular neovascular syndromes.

  该发明涉及一种具有一般式(1)的化合物，其中R1n的n为0、1、2、3或4，特别是R1n的n为0或1，每个R1独立于其他R1，为C1-C3烷基、C1-C3卤代烷基或C1-C3烷氧基，DA为给体-受体基团。该发明还涉及一种化合物或药物制剂，用于治疗癌症或眼内新生血管综合征的方法。
• 2-Amino-1-(o-tolyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide derivates
  申请人：Universität Zürich

  公开号：EP2924040A1

  公开（公告）日：2015-09-30

  The invention relates to a compound characterized by a general formula (1), wherein R1 is OH or CH2OH. The invention relates further to a pharmaceutical preparation comprising at least one of said compounds. A further aspect of the invention the use of said compound or said pharmaceutical preparation in a method of treatment of disease, in particular the treatment of cancer or intraocular neovascular syndromes.

  该发明涉及一种具有一般式（1）特征的化合物，其中R1为OH或CH2OH。该发明进一步涉及一种包含至少一种上述化合物的药物制剂。该发明的另一个方面是将该化合物或该药物制剂用于治疗疾病的方法，特别是用于治疗癌症或眼内新生血管综合征的治疗。
• Inhibition of small ubiquitin-like modifier enzymes with substituted pyrrolo[2,3-b]quinoxalines
  申请人：City of Hope

  公开号：US09045483B2

  公开（公告）日：2015-06-02

  According to the embodiments described herein, a methods for inhibiting small ubiquitin-like modifier enzymes in a cell are provided. Such methods may include administering certain substituted pyrrolo[2,3-b]-quinoxalines to the cell. In some aspects, the small ubiquitin-like modifier enzyme is SUMO E1 or SUMO E2. In some aspects, the methods may be used to inhibit a cancer cell in vitro (e.g., grown in culture) or in vivo (e.g., as part of a tumor in a subject). In other embodiments, methods for treating a cancer, degenerative diseases and viral infection are provided. Such methods may include administering an effective amount of a pharmaceutical composition to a subject having cancer. The pharmaceutical composition may include a small ubiquitin-like modifier inhibitor compound. In some embodiments, the method for treating a disease may further comprise administering one or more DNA-damaging therapy in combination with administration of the pharmaceutical composition.

  根据此处所述的实施例，提供了一种抑制细胞中小泛素样修饰酶的方法。这些方法可以包括将某些取代的吡咯并[2,3-b]-喹啉给予细胞。在某些方面，小泛素样修饰酶是SUMO E1或SUMO E2。在某些方面，这些方法可用于体外（例如在培养中生长）或体内（例如作为受试者肿瘤的一部分）抑制癌细胞。在其他实施例中，提供了治疗癌症、退行性疾病和病毒感染的方法。这些方法可以包括给予含有小泛素样修饰酶抑制剂化合物的药物组合物的有效量给予患有癌症的受试者。在某些实施例中，治疗疾病的方法还可以包括在给予药物组合物的同时给予一种或多种DNA损伤治疗。
• BICYCLIC AND TRICYCLIC INHIBITORS OF SUMOYLATION ENZYMES AND METHODS OF THEIR USE
  申请人：Institute at Lake Nona Sanford-Burnham Medical Research

  公开号：US20130245032A1

  公开（公告）日：2013-09-19

  According to the embodiments described herein, a tricyclic SUMOylation inhibitor compound is provided. In some embodiments, a method for inhibiting a SUMOylation enzyme in a cell is provided. Such a method may include administering a SUMOylation inhibitor compound to the cell. In some aspects, the SUMOylation enzyme is SUMO E1 or SUMO E2. In some aspects, the method may be used to inhibit a cancer cell in vitro (e.g., grown in culture) or in vivo (e.g., as part of a tumor in a subject). In other embodiments, a method for treating a cancer, degenerative diseases and viral infection is provided. Such a method may include administering an effective amount of a pharmaceutical composition to a subject having the cancer. The pharmaceutical composition may include a SUMOylation inhibitor compound. In some embodiments, the method for treating a disease may further comprise administering one or more DNA-damaging therapy in combination with administration of the pharmaceutical composition.

  根据所述实施例，提供了一种三环SUMO化抑制剂化合物。在某些实施例中，提供了一种在细胞中抑制SUMO化酶的方法。这样的方法可能包括向细胞中注射SUMO化抑制剂化合物。在某些方面，SUMO化酶是SUMO E1或SUMO E2。在某些方面，该方法可用于体外（例如在培养中生长）或体内（例如作为受体中的肿瘤的一部分）抑制癌细胞。在其他实施例中，提供了一种治疗癌症、退行性疾病和病毒感染的方法。这样的方法可能包括向患有癌症的受体中注射有效量的制药组合物。该制药组合物可能包括SUMO化抑制剂化合物。在某些实施例中，治疗疾病的方法可能进一步包括在注射制药组合物的同时注射一种或多种DNA损伤治疗方法。
• Use of azolium ylides in the synthesis of con-densed heterocyclic systems from 2-quinox-alylacetonitriles
  作者：S. V. Litvinenko、Yu. M. Volovenko、F. S. Babichev

  DOI：10.1007/bf00531664

  日期：1993.2