2'-(1,3-benzoxazol-2-ylamino)-7',8'-dihydro-1'H-spiro[cyclohexane-1,4'-quinazolin]-5'(6'H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2'-(1,3-benzoxazol-2-ylamino)-7',8'-dihydro-1'H-spiro[cyclohexane-1,4'-quinazolin]-5'(6'H)-one
• 英文别名: 2-(1,3-benzoxazol-2-ylamino)spiro[1,6,7,8-tetrahydroquinazoline-4,1'-cyclohexane]-5-one
• 化学式: C₂₀H₂₂N₄O₂
• 分子量: 350.42
• InChiKey: AZBGHUMVHJKFOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-1,3-苯并噁唑-2-胍 、 环己酮 、 1,3-环己二酮 以 neat (no solvent) 为溶剂， 生成 2'-(1,3-benzoxazol-2-ylamino)-7',8'-dihydro-1'H-spiro[cyclohexane-1,4'-quinazolin]-5'(6'H)-one
  参考文献：
  名称：

  Structure activity relationships of human galactokinase inhibitors

  摘要：

  Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDPgalactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibitor. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.11.061

文献信息

• Structure activity relationships of human galactokinase inhibitors
  作者：Li Liu、Manshu Tang、Martin J. Walsh、Kyle R. Brimacombe、Rajan Pragani、Cordelle Tanega、Jason M. Rohde、Heather L. Baker、Elizabeth Fernandez、Burchelle Blackman、James M. Bougie、William H. Leister、Douglas S. Auld、Min Shen、Kent Lai、Matthew B. Boxer

  DOI：10.1016/j.bmcl.2014.11.061

  日期：2015.2

  Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDPgalactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibitor. Published by Elsevier Ltd.