[1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid | 1588769-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: [1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid
• 英文别名: {[1,2,4]Triazolo[4,3-a]pyridin-6-yl}boronic acid
• CAS: 1588769-41-8
• 化学式: C₆H₆BN₃O₂
• 分子量: 162.944
• InChiKey: LNJFEDPCIDRFNQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.59
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(6-bromo-4-isopropyl-5-oxo-4,5-dihydrothiazolo[5,4-b]pyridin-2-yl)-3-ethylurea 、 [1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid 在 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 1-(6-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-4-isopropyl-5-oxo-4,5-dihydrothiazolo[5,4-b]pyridin-2-yl)-3-ethylurea
  参考文献：
  名称：

  Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy

  摘要：

  Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC = 0.1 mu M) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.080

文献信息

• [EN] HETEROBICYCLIC INHIBITORS OF MAT2A AND METHODS OF USE FOR TREATING CANCER<br/>[FR] INHIBITEURS HÉTÉROBICYCLIQUES DE MAT2A ET PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT DU CANCER
  申请人：AGIOS PHARMACEUTICALS INC

  公开号：WO2020243376A1

  公开（公告）日：2020-12-03

  The present disclosure provides for compounds according to Formula I, Formula II, and their pharmaceutically acceptable salts, tautomers, and/or isotopologues as described in the disclosure. The compounds are inhibitors of methionine adenosyltransferase isoform 2A (MAT2A). Also provided are pharmaceutical compositions and methods of using the compounds for treating cancers, including some cancers in which the gene encoding methylthioadenosine phosphorylase (MTAP) is deleted.

  本公开提供了根据公式I、公式II以及其在公开描述中所述的药用可接受盐、互变异构体和/或同位素体的化合物。这些化合物是蛋氨酸腺苷转移酶同种型2A（MAT2A）的抑制剂。还提供了药物组合物和使用这些化合物治疗癌症的方法，包括一些编码甲硫腺苷磷酸化酶（MTAP）的基因被删除的癌症。
• WO2023/4280
  申请人：——

  公开号：——

  公开（公告）日：——
• Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy
  作者：Ramesh R. Kale、Manoj G. Kale、David Waterson、Anandkumar Raichurkar、Shahul P. Hameed、M.R. Manjunatha、B.K. Kishore Reddy、Krishnan Malolanarasimhan、Vikas Shinde、Krishna Koushik、Lalit Kumar Jena、Sreenivasaiah Menasinakai、Vaishali Humnabadkar、Prashanti Madhavapeddi、Halesha Basavarajappa、Sreevalli Sharma、Radha Nandishaiah、K.N. Mahesh Kumar、Samit Ganguly、Vijaykamal Ahuja、Sheshagiri Gaonkar、C.N. Naveen Kumar、Derek Ogg、P. Ann Boriack-Sjodin、Vasan K. Sambandamurthy、Sunita M. de Sousa、Sandeep R. Ghorpade

  DOI：10.1016/j.bmcl.2013.12.080

  日期：2014.2

  Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC = 0.1 mu M) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration. (C) 2014 Elsevier Ltd. All rights reserved.