4-[[2-[6-[(4-甲基-1-哌嗪基)羰基]-2-萘基]乙基]氨基]-6-喹唑啉甲腈 | 1449228-40-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-[[2-[6-[(4-甲基-1-哌嗪基)羰基]-2-萘基]乙基]氨基]-6-喹唑啉甲腈
• 英文名称: senexin B
• 英文别名: Senexin B；4-[2-[6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl]ethylamino]quinazoline-6-carbonitrile
• CAS: 1449228-40-3
• 化学式: C₂₇H₂₆N₆O
• 分子量: 450.543
• InChiKey: VNADJTWHOAMTLY-UHFFFAOYSA-N

物化性质

• 沸点：
  724.8±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  >22.6mg/mL，溶于 DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为产物：
  描述：

  6-碘-4(H)-喹唑啉酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 氯化亚砜 、 三乙胺 作用下， 以 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 4-[[2-[6-[(4-甲基-1-哌嗪基)羰基]-2-萘基]乙基]氨基]-6-喹唑啉甲腈
  参考文献：
  名称：

  [EN] INHIBITORS OF CDK8/19 FOR USE IN TREATING ESTROGEN RECEPTOR POSITIVE BREAST CANCER
  [FR] INHIBITEURS DE CDK8/19 POUR UTILISATION DANS LE TRAITEMENT DU CANCER DU SEIN À RÉCEPTEURS D'ŒSTROGÈNE POSITIFS

  摘要：

  本发明提供了一种CDK8/19选择性抑制剂，用于治疗ER+乳腺癌患者，包括对抗雌激素治疗产生抗药性的乳腺癌。在某些实施例中，CDK8/19选择性抑制剂与抗雌激素治疗联合使用。在某些实施例中，CDK8/19选择性抑制剂与HER2靶向药物联合使用，用于治疗ER+ HER2+乳腺癌患者。

  公开号：

  WO2014134169A1

文献信息

• [EN] CDK8/CDK19 SELECTIVE INHIBITORS AND THEIR USE IN ANTI-METASTATIC AND CHEMOPREVENTATIVE METHODS FOR CANCER<br/>[FR] INHIBITEURS SÉLECTIFS DE CDK8/CDK19 ET LEUR UTILISATION DANS DES MÉTHODES ANTI-MÉTASTATIQUES ET CHIMIOPRÉVENTIVES DU CANCER
  申请人：SENEX BIOTECHNOLOGY INC

  公开号：WO2013116786A1

  公开（公告）日：2013-08-08

  The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI -related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.

  本发明涉及化合物和方法，用于抑制细胞周期蛋白依赖性激酶抑制剂（CDKI）通路。更具体地说，本发明涉及用于研究和干预衰老相关和其他CDKI相关疾病的化合物和方法。本发明提供了具有改善溶解度和/或效力的新化合物，以及它们的使用方法。在各种方面，本发明涉及癌症的治疗。本发明提供了用于化学预防和预防肿瘤复发或转移的方法。本发明还提供了用于治疗某些癌症类型的诊断技术。本发明利用CDK8/19的特定抑制剂和/或测量患者的CDK8水平。
• METHODS AND COMPOSITIONS FOR TREATMENT OF HER-POSITIVE CANCERS
  申请人：UNIVERSITY OF SOUTH CAROLINA

  公开号：US20170196868A1

  公开（公告）日：2017-07-13

  Cancers that overexpress tyrosine kinase receptors of HER family are treated with drugs acting on these receptors. Although HER-targeting drugs have revolutionized the treatment of HER-positive cancers, high rates of primary and treatment-emergent resistance limit their clinical utility. The present inventors have now discovered that combining HER-targeting drugs with a selective inhibitor of CDK8/19 greatly improves the efficacy of such drugs, offering an improved approach to the treatment of HER-positive cancers.
• COMPOUNDS FOR TREATMENT OF HYPOPROLIFERATIVE DISORDERS
  申请人：LU LICENSE AB

  公开号：US20190111034A1

  公开（公告）日：2019-04-18

  The present invention relates to the use of CDK8 and/or CDK19 inhibitors in the treatment of ribosomopathies as well as conditions characterized by reduced number of hematopoietic stem cells and/or progenitor cells; and bone anabolic disorders.
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• US9321737B2
  申请人：——

  公开号：US9321737B2

  公开（公告）日：2016-04-26