六氢吡咯并[1,2-A]吡嗪-4-酮 | 1000577-63-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 六氢吡咯并[1,2-A]吡嗪-4-酮
• 英文名称: hexahydropyrrolo[1,2-a]pyrazin-4-one
• 英文别名: Hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one；2,3,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-4-one
• CAS: 1000577-63-8
• 化学式: C₇H₁₂N₂O
• mdl: MFCD09878659
• 分子量: 140.185
• InChiKey: HAAZJWVQKLGNDT-UHFFFAOYSA-N

物化性质

• 沸点：
  284.4±29.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)acetic acid 、 六氢吡咯并[1,2-A]吡嗪-4-酮 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-[2-(5-Chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-1,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-4-one
  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] NOVEL C28-AMIDES WITH C3-MODIFICATIONS OF TRITERPENE DERIVATIVES AS HIV INHIBITORS<br/>[FR] NOUVEAUX AMIDES EN C28 AVEC DES MODIFICATIONS EN C3 DE DÉRIVÉS TRITERPÉNIQUES COMME INHIBITEURS DU VIH
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2017025899A1

  公开（公告）日：2017-02-16

  Formula (I) The present invention relates to novel C28-amides with C3-modifications of triterpene compounds of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X, and Y are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) useful for the therapeutic treatment of viral mediated diseases and particularly HIV mediated diseases.

  本发明涉及新型的C28酰胺，具有C3修饰的三萜化合物，其公式为(I)；或药用可接受的盐、药用可接受的溶剂化物、药用可接受的水合物、互变异构体、立体异构体、前药或它们的组合，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、X和Y按本发明中定义。本发明还涉及包含公式(I)化合物的药物组合物，用于治疗病毒介导的疾病，特别是HIV介导的疾病。
• FUSED RING DERIVATIVE USED AS FGFR4 INHIBITOR
  申请人：JACOBIO PHARMACEUTICALS CO., LTD.

  公开号：US20210163478A1

  公开（公告）日：2021-06-03

  A compound represented by formula I or a pharmaceutically acceptable salt thereof and a use thereof in preparing a drug for treating, stopping or preventing a disease or disorder mediated by FGFR4 activity.

  由式I表示的化合物或其药学上可接受的盐以及其在制备用于治疗、阻止或预防由FGFR4活性介导的疾病或紊乱的药物中的用途。
• [EN] HETEROARYLCARBOXAMIDE DERIVATIVES AS PLASMA KALLIKREIN INHIBITORS<br/>[FR] UTILISATION DE DÉRIVÉS HÉTÉROARYLCARBOXAMIDES COMME INHIBITEURS DE LA KALLICRÉINE PLASMATIQUE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2017072021A1

  公开（公告）日：2017-05-04

  The present invention relates to compounds of general formula (I), wherein D 1 to D 3, -A-, n, R 1, R 2, Y 1, L and y2 are defined as in claim 1, which have valuable pharmacological properties, in particular are inhibitors of plasma kallikrein. The compounds are suitable for treatment and prevention of diseases which can be influenced by inhibition of plasma kallikrein, such as diabetic complications, particularly in the treatment of retinal vascular permeability associated with diabetic retinopathy and diabetic macular edema.

  本发明涉及一般式（I）的化合物，其中D1至D3，-A-，n，R1，R2，Y1，L和Y2的定义如权利要求书中所述，具有有价值的药理特性，特别是是血浆激肽酶的抑制剂。这些化合物适用于治疗和预防可以通过抑制血浆激肽酶而受影响的疾病，例如糖尿病并发症，特别是治疗与糖尿病视网膜病变和糖尿病黄斑水肿相关的视网膜血管通透性。
• [EN] BICYCLIC RING SYSTEM SUBSTITUTED AMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS<br/>[FR] PHÉNOLS À FONCTIONNALITÉ AMIDE SUBSTITUÉS PAR UN SYSTÈME CYCLIQUE BICYCLIQUE EN TANT QUE MÉDICAMENTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012080456A1

  公开（公告）日：2012-06-21

  This invention relates to bicyclic ring system substituted amide functionalized phenols of general formula 1, their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

  这项发明涉及通式1的双环环系统取代酰胺功能化酚，其用作CXCR2活性抑制剂，含有这些化合物的药物组合物，以及将其用作治疗和/或预防呼吸系统或消化系统疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。
• BICYCLIC RING SYSTEM SUBSTITUTED AMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS
  申请人：GIOVANNINI Riccardo

  公开号：US20120329773A1

  公开（公告）日：2012-12-27

  This invention relates to bicyclic ring system substituted amide functionalized phenols of general formula 1, their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

  这项发明涉及通式1的双环环系统取代酰胺功能化酚，其用作CXCR2活性抑制剂，含有相同化合物的药物组合物，以及将其用作治疗和/或预防呼吸道或胃肠道疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。