(1S)-1-(5-{ [1-(2,6-difluorobenzyl)-1H-pyrazol-3-yl]amino}-1,3,4-thiadiazol-2-yl)-1-(4-methyl-1,3-thiazol-2-yl)ethanol | 1251929-37-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (1S)-1-(5-{ [1-(2,6-difluorobenzyl)-1H-pyrazol-3-yl]amino}-1,3,4-thiadiazol-2-yl)-1-(4-methyl-1,3-thiazol-2-yl)ethanol
• 英文别名: (1S)-1-[5-({1-[(2,6-difluorophenyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol；(1s)-1-(5-{[1-(2,6-Difluorobenzyl)-1h-Pyrazol-3-Yl]amino}-1,3,4-Thiadiazol-2-Yl)-1-(4-Methyl-1,3-Thiazol-2-Yl)ethanol；(1S)-1-[5-[[1-[(2,6-difluorophenyl)methyl]pyrazol-3-yl]amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol
• CAS: 1251929-37-9
• 化学式: C₁₈H₁₆F₂N₆OS₂
• 分子量: 434.493
• InChiKey: UXRSVTXAGGLLHU-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-羟基-2-(4-甲基-1,3-噻唑-2-基)丙酸乙酯 在 硫酸 、 一水合肼 作用下， 以 甲醇 、 乙醇 、 异丙胺 、 异丙醇 、 乙腈 为溶剂， 反应 8.0h， 生成 (1R)-1-[5-({1-[(2,6-difluorophenyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol 、 (1S)-1-(5-{ [1-(2,6-difluorobenzyl)-1H-pyrazol-3-yl]amino}-1,3,4-thiadiazol-2-yl)-1-(4-methyl-1,3-thiazol-2-yl)ethanol
  参考文献：
  名称：

  (PYRAZOL-3-YL)-1,3,4-THIADIAZOL-2-AMINE AND (PYRAZOL-3-YL)-1,3,4-THIAZOL-2-AMINE COMPOUNDS

  摘要：

  一个由Formula (I)组成的化合物 其中：X为N且Y为CR5，或者X为C且Y为S；Z从N和CH中选择；R1从H和Me中选择；R2从H、OH、OMe和Me中选择；每个R3独立地从C1-3烷基、F、Cl、Br、CF3和NH2中选择；R4从Me、CF3、NO2和CHF2中选择；R5从H、Me和CHF2中选择；R6从H和Me中选择；p为0-3，提供了含有它们的组合物，它们在治疗中的使用，例如在结核病治疗中的使用，以及制备这类化合物的方法。

  公开号：

  US20120095064A1

文献信息

• [EN] ( PYRAZOL-3-YL) -1, 3, 4-THIADIAZOL-2-AMINE AND ( PYRAZOL-3-YL) -1, 3, 4-THIAZOL-2-AMINE COMPOUNDS<br/>[FR] COMPOSÉS DE (PYRAZOL-3-YL)-1,3,4-THIADIAZOL-2-AMINE ET DE (PYRAZOL-3-YL)-1,3,4-THIAZOL-2-AMINE
  申请人：GLAXO GROUP LTD

  公开号：WO2010118852A1

  公开（公告）日：2010-10-21

  wherein: either X is N and Y is CR5 or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and Me; R2 is selected from H, OH, OMe and Me; each R3 is independently selected from C1-3alkyl, F, Cl, Br, CF3 and NH2; R4 is selected from Me, CF3, NO2 and CHF2; R5 is selected from H, Me and CHF2; R6 is selected from H and Me; and p is 0-3, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.

  提供其中的化学式：其中，要么X是N且Y是CR5，要么X是C且Y是S；Z从N和CH中选择；R1从H和Me中选择；R2从H、OH、OMe和Me中选择；每个R3独立地从C1-3烷基、F、Cl、Br、CF3和NH2中选择；R4从Me、CF3、NO2和CHF2中选择；R5从H、Me和CHF2中选择；R6从H和Me中选择；p为0-3。提供了包含它们的组合物，它们在治疗中的应用，例如在结核病的治疗中，以及制备这些化合物的方法。
• Methyl-Thiazoles: A Novel Mode of Inhibition with the Potential to Develop Novel Inhibitors Targeting InhA in Mycobacterium tuberculosis
  作者：Pravin S. Shirude、Prashanti Madhavapeddi、Maruti Naik、Kannan Murugan、Vikas Shinde、Radha Nandishaiah、Jyothi Bhat、Anupriya Kumar、Shahul Hameed、Geoffrey Holdgate、Gareth Davies、Helen McMiken、Naina Hegde、Anisha Ambady、Janani Venkatraman、Manoranjan Panda、Balachandra Bandodkar、Vasan K. Sambandamurthy、Jon A. Read

  DOI：10.1021/jm4012033

  日期：2013.11.14

  InhA is a well validated Mycobacterium tuberculosis (Mtb) target as evidenced by the clinical success of isoniazid. Translating enzyme inhibition to bacterial cidality by targeting the fatty acid substrate site of InhA remains a daunting challenge. The recent disclosure of a methyl-thiazole series demonstrates that bacterial cidality can be achieved with potent enzyme inhibition and appropriate physicochemical properties. In this study, we report the molecular mode of action of a lead methyl-thiazole, along with analogues with improved CYP inhibition profile. We have identified a novel mechanism of InhA inhibition characterized by a hitherto unreported "Y158-out" inhibitor-bound conformation of the protein that accommodates a neutrally charged "warhead". An additional novel hydrophilic interaction with protein residue M98 allows the incorporation of favorable physicochemical properties for cellular activity. Notably, the methyl-thiazole prefers the NADH-bound form of the enzyme with a K-d of similar to 13.7 nM, as against the NAD(+)-bound form of the enzyme.
• ( PYRAZOL-3-YL) -1, 3, 4-THIADIAZOL-2-AMINE AND ( PYRAZOL-3-YL) -1, 3, 4-THIAZOL-2-AMINE COMPOUNDS
  申请人：Glaxo Group Limited

  公开号：EP2419426A1

  公开（公告）日：2012-02-22
• US8524750B2
  申请人：——

  公开号：US8524750B2

  公开（公告）日：2013-09-03
• (PYRAZOL-3-YL)-1,3,4-THIADIAZOL-2-AMINE AND (PYRAZOL-3-YL)-1,3,4-THIAZOL-2-AMINE COMPOUNDS
  申请人：Ballell Pages Lluis

  公开号：US20120095064A1

  公开（公告）日：2012-04-19

  A compound of Formula (I) wherein: either X is N and Y is CR 5 or X is C and Y is S; Z is selected from N and CH; R 1 is selected from H and Me; R 2 is selected from H, OH, OMe and Me; each R 3 is independently selected from C 1-3 alkyl, F, Cl, Br, CF 3 and NH 2 ; R 4 is selected from Me, CF 3 , NO 2 and CHF 2 ; R 5 is selected from H, Me and CHF 2 ; R 6 is selected from H and Me; and p is 0-3, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.

  一个由Formula (I)组成的化合物 其中：X为N且Y为CR5，或者X为C且Y为S；Z从N和CH中选择；R1从H和Me中选择；R2从H、OH、OMe和Me中选择；每个R3独立地从C1-3烷基、F、Cl、Br、CF3和NH2中选择；R4从Me、CF3、NO2和CHF2中选择；R5从H、Me和CHF2中选择；R6从H和Me中选择；p为0-3，提供了含有它们的组合物，它们在治疗中的使用，例如在结核病治疗中的使用，以及制备这类化合物的方法。