2-甲基-5,6,7,8-四氢-[1,2,4]噻唑并[1,5-A]吡嗪 | 914654-92-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-甲基-5,6,7,8-四氢-[1,2,4]噻唑并[1,5-A]吡嗪
• 中文别名: 2-甲基-5,6,7,8-四氢-[1,2,4]噻唑并[1,5-a]吡嗪
• 英文名称: 2-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine
• CAS: 914654-92-5
• 化学式: C₆H₁₀N₄
• mdl: MFCD11044798
• 分子量: 138.172
• InChiKey: XJQLZEZGFIWRKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-甲基-5,6,7,8-四氢-[1,2,4]噻唑并[1,5-A]吡嗪 、 2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)acetic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-1-(2-methyl-6,8-dihydro-5H-[1,2,4]triazolo[1,5-a]pyrazin-7-yl)ethanone
  参考文献：
  名称：

  Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors

  摘要：

  The carboxylesterase Notum is a key negative regulator of the Wnt signaling pathway by mediating the depalmitoleoylation of Wnt proteins. Our objective was to discover potent small molecule inhibitors of Notum suitable for exploring the regulation of Wnt signaling in the central nervous system. Scaffold-hopping from thienopyrimidine acids 1 and 2, supported by X-ray structure determination, identified 3-methylimidazolin-4-one amides 20-24 as potent inhibitors of Notum with activity across three orthogonal assay formats (biochemical, extra-cellular, occupancy). A preferred example 24 demonstrated good stability in mouse microsomes and plasma, and cell permeability in the MDCK-MDR1 assay albeit with modest P-gp mediated efflux. Pharmacokinetic studies with 24 were performed in vivo in mouse with single oral administration of 24 showing good plasma exposure and reasonable CNS penetration. We propose that 24 is a new chemical tool suitable for cellular studies to explore the fundamental biology of Notum.

  DOI：

  10.1016/j.bmcl.2019.126751

文献信息

• [EN] PYRIMIDO[5,4-d]PYRIMIDINE DERIVATIVES AS ENT INHIBITORS FOR THE TREATMENT OF CANCERS, AND COMBINATION THEREOF WITH ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE PYRIMIDO[5,4-D]PYRIMIDINE SERVANT D'INHIBITEURS D'ENT POUR LE TRAITEMENT DE CANCERS, ET LEUR COMBINAISON AVEC DES ANTAGONISTES DU RÉCEPTEUR DE L'ADÉNOSINE
  申请人：ITEOS BELGIUM SA

  公开号：WO2021170797A1

  公开（公告）日：2021-09-02

  The present invention relates to pyrimido[5,4-d]pyrimidine derivatives of formula (I), including pharmaceutically acceptable salts and solvates thereof. Compounds of the invention are inhibitors of ENT family transporter, especially of ENT1, and are useful as therapeutic compounds for the treatment of cancers. The invention also relates to the combined use of the pyrimido[5,4-d]pyrimidine derivatives with an adenosine receptor antagonist, for the treatment of cancers.

  本发明涉及式(I)的嘧啶并[5,4-d]嘧啶衍生物，包括其药用可接受盐和溶剂化合物。本发明的化合物是ENT家族转运蛋白的抑制剂，特别是ENT1的抑制剂，并且可用作治疗癌症的治疗化合物。该发明还涉及将嘧啶并[5,4-d]嘧啶衍生物与腺苷受体拮抗剂联合使用，用于治疗癌症。
• [EN] SUBSTITUTED 1,5-NAPHTHYRIDINES OR QUINOLINES AS ALK5 INHIBITORS<br/>[FR] 1,5-NAPHTYRIDINES OU QUINOLÉINES SUBSTITUÉES EN TANT QU'INHIBITEURS D'ALK5
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2021102468A1

  公开（公告）日：2021-05-27

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

  本公开提供了激活素受体样激酶5（ALK5）的抑制剂。还公开了调节ALK5活性的方法和通过ALK5介导的疾病的治疗方法。
• Quinoline derivatives as neurokinin receptor antagonists
  申请人：Carling William Robert

  公开号：US20090054440A1

  公开（公告）日：2009-02-26

  The present invention relates to substituted quinoline hydrazides of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y and Z are defined herein, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-2 and/or neurokinin-3 (NK-3) receptors. These compounds can thus be used in methods of treatment to suppress and treat such disorders.

  本发明涉及式(I)所示的取代喹啉酰肼：其中R1、R2、R3、R4、R5、X、Y和Z在此定义，包含它们的药物组合物及其在治疗由神经激肽-2和/或神经激肽-3 (NK-3)受体介导的疾病中的用途。因此，这些化合物可用于治疗方法，以抑制和治疗这些疾病。
• [EN] SUBSTITUTED SULFONAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE SULFONAMIDES SUBSTITUÉS
  申请人：GRUENENTHAL GMBH

  公开号：WO2009090055A1

  公开（公告）日：2009-07-23

  The invention relates to substituted sulfonamide derivatives of the general formula (I'); processes for their preparation, medicaments containing these compounds, and the use of substituted sulfonamide derivatives for the preparation of medicaments

  该发明涉及一般式（I'）的取代磺胺基衍生物，其制备方法，含有这些化合物的药物，以及用于制备药物的取代磺胺基衍生物的用途
• ALK5 INHIBITORS
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20200188370A1

  公开（公告）日：2020-06-18

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

  本公开提供抑制活性素受体样激酶5（ALK5）的抑制剂。还公开了调节ALK5活性的方法以及治疗由ALK5介导的疾病的方法。