2-(1,3-benzoxazol-2-ylamino)-4-(4-chloro-2-methylpyrazol-3-yl)-4,6,7,8-tetrahydro-1H-quinazolin-5-one | 1428529-44-5

• 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)-4-(4-chloro-2-methylpyrazol-3-yl)-4,6,7,8-tetrahydro-1H-quinazolin-5-one
• CAS: 1428529-44-5
• 化学式: C₁₉H₁₇ClN₆O₂
• 分子量: 396.836
• InChiKey: JQEYWPMRWCRGEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-1,3-苯并噁唑-2-胍 、 4-氯-1-甲基-1H-吡唑-5-甲醛 、 1,3-环己二酮 以 neat (no solvent) 为溶剂， 生成 2-(1,3-benzoxazol-2-ylamino)-4-(4-chloro-2-methylpyrazol-3-yl)-4,6,7,8-tetrahydro-1H-quinazolin-5-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

• [EN] GALACTOKINASE INHIBITORS FOR THE TREATMENT AND PREVENTION OF ASSOCIATED DISEASES AND DISORDERS<br/>[FR] INHIBITEURS DE GALACTOKINASE POUR LE TRAITEMENT ET LA PRÉVENTION DE MALADIES ET DE TROUBLES ASSOCIÉS
  申请人：US HEALTH

  公开号：WO2013043192A1

  公开（公告）日：2013-03-28

  Disclosed are inhibitors of human galactokinase of formula (1) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I)

  本发明涉及一种公开的人类半乳糖激酶抑制剂，其化学式为（1），可用于治疗或预防半乳糖激酶介导的疾病或疾病，例如半乳糖血症。还公开了一种包含药学上可接受的载体和本发明中至少一种抑制剂的组合物，以及一种在哺乳动物中治疗或预防该类疾病或疾病的方法。化学式（I）
• Galactokinase inhibitors for the treatment and prevention of associated diseases and disorders
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：US10471061B2

  公开（公告）日：2019-11-12

  Disclosed are inhibitors of human galactokinase of formula (I) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I).

  本发明公开了式(I)的人半乳糖激酶抑制剂，可用于治疗或预防半乳糖激酶介导的疾病或紊乱，如半乳糖血症。还公开了一种包含药学上可接受的载体和至少一种本发明抑制剂的组合物，以及一种治疗或预防哺乳动物中此类疾病或紊乱的方法。式 (I).
• GALACTOKINASE INHIBITORS FOR THE TREATMENT AND PREVENTION OF ASSOCIATED DISEASES AND DISORDERS
  申请人：Boxer Matthew B.

  公开号：US20140288100A1

  公开（公告）日：2014-09-25

  Disclosed are inhibitors of human galactokinase of formula (1) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I)
• US9447087B2
  申请人：——

  公开号：US9447087B2

  公开（公告）日：2016-09-20
• 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.