2-(5,6-dimethylfuro[2,3-d]pyrimidin-4-ylthio)acetic acid | 1365062-95-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 2-(5,6-dimethylfuro[2,3-d]pyrimidin-4-ylthio)acetic acid
• 英文别名: 2-(5,6-Dimethylfuro[2,3-d]pyrimidin-4-yl)sulfanylacetic acid
• CAS: 1365062-95-8
• 化学式: C₁₀H₁₀N₂O₃S
• 分子量: 238.267
• InChiKey: GVSJMIJIAQKDRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5,6-Dimethylfuro[2,3-d]pyrimidin-4(3h)-one 在 水 、 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.17h， 生成 2-(5,6-dimethylfuro[2,3-d]pyrimidin-4-ylthio)acetic acid
  参考文献：
  名称：

  INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE

  摘要：

  揭示了用于治疗、管理和预防影响骨骼的疾病和紊乱的化合物。特定的化合物是Notum果胶乙酰酶的强效抑制剂，化学结构如下：其中E、G、Y、Z、R1、R2和R3如本文所定义。

  公开号：

  US20120065200A1

文献信息

• INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE
  申请人：BARBOSA Joseph

  公开号：US20120065200A1

  公开（公告）日：2012-03-15

  Compounds are disclosed for the treatment, management and prevention of diseases and disorders affecting the bone. Particular compounds are potent inhibitors of Notum Pectinacetylesterase, and are of the formula: wherein E, G, Y, Z, R 1 , R 2 , and R 3 are defined herein.

  揭示了用于治疗、管理和预防影响骨骼的疾病和紊乱的化合物。特定的化合物是Notum果胶乙酰酶的强效抑制剂，化学结构如下：其中E、G、Y、Z、R1、R2和R3如本文所定义。
• [EN] INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE<br/>[FR] INHIBITEURS DE LA NOTUM PECTINE ACÉTYLESTÉRASE ET PROCÉDÉS POUR LEUR UTILISATION
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2012037141A1

  公开（公告）日：2012-03-22

  Compounds are disclosed for the treatment, management and prevention of diseases and disorders affecting the bone. Particular compounds are potent inhibitors of Notum Pectinacetylesterase, and are of the formula: wherein E, G, Y, Z, R1, R2, and R3 are defined herein.
• Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors
  作者：Benjamin N. Atkinson、David Steadman、William Mahy、Yuguang Zhao、James Sipthorp、Elliott D. Bayle、Fredrik Svensson、George Papageorgiou、Fiona Jeganathan、Sarah Frew、Amy Monaghan、Magda Bictash、E. Yvonne Jones、Paul V. Fish

  DOI：10.1016/j.bmcl.2019.126751

  日期：2020.2

  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.