[(6-甲基噻吩并[2,3-d]嘧啶-4-基)硫基]乙酸 | 890014-20-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: [(6-甲基噻吩并[2,3-d]嘧啶-4-基)硫基]乙酸
• 英文名称: [(6-methylthieno[2,3-d]pyrimidin-4-yl)thio]acetic acid
• 英文别名: 2-((6-methylthieno[2,3-d]pyrimidin-4-yl)thio)acetic acid；2-(6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetic acid
• CAS: 890014-20-7
• 化学式: C₉H₈N₂O₂S₂
• 分子量: 240.307
• InChiKey: UADAVIOFIOBDAS-UHFFFAOYSA-N

物化性质

• 沸点：
  462.3±45.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为产物：
  描述：

  4-氯-6-甲基噻吩[2,3-D]嘧啶 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 [(6-甲基噻吩并[2,3-d]嘧啶-4-基)硫基]乙酸
  参考文献：
  名称：

  Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase

  摘要：

  A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3-d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4-yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.021

文献信息

• Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2
  作者：Andriy G. Golub、Volodymyr G. Bdzhola、Nadiia V. Briukhovetska、Anatoliy O. Balanda、Olexander P. Kukharenko、Igor M. Kotey、Olga V. Ostrynska、Sergiy M. Yarmoluk

  DOI：10.1016/j.ejmech.2010.12.025

  日期：2011.3

  A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC50 values are 0.1 mu M and 0.125 mu M, respectively). Structure activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2. (C) 2011 Elsevier Masson SAS. All rights reserved.
• 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.
• INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：EP2616471B1

  公开（公告）日：2014-12-31