1-(Cyclohexylmethyl)-1H-pyrazol-3-amine | 1184504-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 英文名称: 1-(Cyclohexylmethyl)-1H-pyrazol-3-amine
• 英文别名: 1-(cyclohexylmethyl)pyrazol-3-amine
• CAS: 1184504-62-8
• 化学式: C₁₀H₁₇N₃
• 分子量: 179.265
• InChiKey: OICTYTRZSDWUIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-(benzofuran-3-carbonyl)-4-(3-ethyl-1-methyl-1H-pyrazole-5-carboxamido)pyrrolidine-2-carboxylic acid 、 1-(Cyclohexylmethyl)-1H-pyrazol-3-amine 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以30%的产率得到(4R)-1-(1-benzofuran-3-ylcarbonyl)-N-[1-(cyclohexylmethyl)-1H-pyrazol-3-yl]-4-{[(3-ethyl-1-methyl-1H-pyrazol-5-yl)carbonyl]amino}-L-prolinamide
  参考文献：
  名称：

  Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium tuberculosis InhA

  摘要：

  Tuberculosis (TB) is one of the world's oldest and deadliest diseases, killing a person every 20 s. InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis, is the target of the frontline antitubercular drug isoniazid (INH). Compounds that directly target InhA and do not require activation by mycobacterial catalase peroxidase KatG are promising candidates for treating infections caused by INH resistant strains. The application of the encoded library technology (ELT) to the discovery of direct InhA inhibitors yielded compound 7 endowed with good enzymatic potency but with low antitubercular potency. This work reports the hit identification, the selected strategy for potency optimization, the structure-activity relationships of a hundred analogues synthesized, and the results of the in vivo efficacy studies performed with the lead compound 65.

  DOI：

  10.1021/jm401326j

文献信息

• THIAZOLYL-CONTAINING COMPOUNDS FOR TREATING PROLIFERATIVE DISEASES
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20170233411A1

  公开（公告）日：2017-08-17

  The present disclosure provides thiazolyl-containing compounds of Formula (I), (II), or (III). The compounds described herein may be able to inhibit protein kinases (e.g., Src family kinases (e.g., hemopoietic cell kinase (HCK)), Bruton's tyrosine kinase (BTK)) and may be useful in treating and/or preventing proliferative diseases (e.g., myelodysplasia, leukemia, lymphoma (e.g., Waldenstrom's macroglobulinemia)) and in inducing apoptosis in a cell (e.g., malignant blood cell). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
• Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of <i>Mycobacterium tuberculosis</i> InhA
  作者：Lourdes Encinas、Heather O’Keefe、Margarete Neu、Modesto J. Remuiñán、Amish M. Patel、Ana Guardia、Christopher P. Davie、Natalia Pérez-Macías、Hongfang Yang、Maire A. Convery、Jeff A. Messer、Esther Pérez-Herrán、Paolo A. Centrella、Daniel Álvarez-Gómez、Matthew A. Clark、Sophie Huss、Gary K. O’Donovan、Fátima Ortega-Muro、William McDowell、Pablo Castañeda、Christopher C. Arico-Muendel、Stane Pajk、Joaquín Rullás、Iñigo Angulo-Barturen、Emilio Álvarez-Ruíz、Alfonso Mendoza-Losana、Lluís Ballell Pages、Julia Castro-Pichel、Ghotas Evindar

  DOI：10.1021/jm401326j

  日期：2014.2.27

  Tuberculosis (TB) is one of the world's oldest and deadliest diseases, killing a person every 20 s. InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis, is the target of the frontline antitubercular drug isoniazid (INH). Compounds that directly target InhA and do not require activation by mycobacterial catalase peroxidase KatG are promising candidates for treating infections caused by INH resistant strains. The application of the encoded library technology (ELT) to the discovery of direct InhA inhibitors yielded compound 7 endowed with good enzymatic potency but with low antitubercular potency. This work reports the hit identification, the selected strategy for potency optimization, the structure-activity relationships of a hundred analogues synthesized, and the results of the in vivo efficacy studies performed with the lead compound 65.