Thiazolo[4,5-b]pyridine,2-(1-piperazinyl)- | 1095539-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Thiazolo[4,5-b]pyridine,2-(1-piperazinyl)-
• 英文别名: 2-piperazin-1-yl-[1,3]thiazolo[4,5-b]pyridine
• CAS: 1095539-28-8
• 化学式: C₁₀H₁₂N₄S
• 分子量: 220.298
• InChiKey: HQMNUDXHVWGNNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  反式-1,2-环己二羧酸酐 、 Thiazolo[4,5-b]pyridine,2-(1-piperazinyl)- 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 (1R,2R)-N-(1-cyanocyclopropyl)-2-[(4-[1,3]thiazolo[4,5-b]pyridin-2-ylpiperazin-1-yl)carbonyl]cyclohexanecarboxamide
  参考文献：
  名称：

  Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition

  摘要：

  The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.012
• 作为产物：
  描述：

  Tert-butyl 4-([1,3]thiazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate 生成 Thiazolo[4,5-b]pyridine,2-(1-piperazinyl)-
  参考文献：
  名称：

  Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition

  摘要：

  The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.012

文献信息

• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2021123291A1

  公开（公告）日：2021-06-24

  The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations; or alpha synucleinopathies, in particular Parkinson's disease, dementia due to Parkinson's (or neurocognitive disorder due to Parkinson's disease), dementia with Lewy bodies, multiple system atrophy, or alpha synucleinopathy caused by Gaucher's disease.

  本发明涉及O-GlcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗抑制OGA有益的疾病的用途，例如tau病变，特别是阿尔茨海默病或进行性上行性核瘫痪；以及伴有tau病理的神经退行性疾病，特别是由C9ORF72突变引起的肌萎缩侧索硬化或额颞叶痴呆；或α-突触核蛋白病，特别是帕金森病、帕金森病引起的痴呆（或由帕金森病引起的神经认知障碍）、带有Lewy小体的痴呆、多系统萎缩，或由高雪氏病引起的α-突触核蛋白病。
• SMALL MOLECULE MODULATORS OF PANK
  申请人：St. Jude Children's Research Hospital

  公开号：US20220185796A1

  公开（公告）日：2022-06-16

  The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• [EN] CYANOCYCLOPROPYLCARBOXAMIDES AS CATHEPSIN INHIBITORS<br/>[FR] CYANOCYCLOPROPYLCARBOXAMIDES EN TANT QU'INHIBITEURS DE CATHEPSINE
  申请人：ASTRAZENECA AB

  公开号：WO2009001127A1

  公开（公告）日：2008-12-31

  [EN] The present invention relates to compounds of formula (I) for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases, including cathepsins B, K, C, F, H, L, O, S, W and X. Of particular interest are diseases associated with Cathepsin K.
  [FR] L'invention concerne des composés de formule (I) destinés au traitement de maladies associées à l'activité de la cystéine protéase. Les composés selon l'invention sont des inhibiteurs réversibles de cystéines protéases, notamment des cathepsines B, K, C, F, H, L, O, S, W et X. Les maladies associées à la cathepsine K font l'objet d'un intérêt particulier.
• [EN] SMALL MOLECULE MODULATORS OF PANK<br/>[FR] MODULATEURS À PETITES MOLÉCULES DE PANK
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2020198526A2

  公开（公告）日：2020-10-01

  The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition
  作者：Alexander G. Dossetter、Jonathan Bowyer、Calum R. Cook、James J. Crawford、Jonathan E. Finlayson、Nicola M. Heron、Christine Heyes、Adrian J. Highton、Julian A. Hudson、Anja Jestel、Stephan Krapp、Philip A. MacFaul、Thomas M. McGuire、Andrew D. Morley、Jeffrey J. Morris、Ken M. Page、Lyn Rosenbrier Ribeiro、Helen Sawney、Stefan Steinbacher、Caroline Smith

  DOI：10.1016/j.bmcl.2012.07.012

  日期：2012.9

  The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.