(S)-2-fluoropropan-1-amine | 1494676-44-6

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 英文名称: (S)-2-fluoropropan-1-amine
• 英文别名: (2S)-2-fluoropropan-1-amine；(S)-2-Fluoropropan-1-amine
• CAS: 1494676-44-6
• 化学式: C₃H₈FN
• 分子量: 77.1016
• InChiKey: FCZZMLAMPPXMOZ-VKHMYHEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid 、 (S)-2-fluoropropan-1-amine 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-N-(2-fluoropropyl)-1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide
  参考文献：
  名称：

  Azaindoles: Noncovalent DprE1 Inhibitors from Scaffold Morphing Efforts, Kill Mycobacterium tuberculosis and Are Efficacious in Vivo

  摘要：

  We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-beta-D-ribose2'-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.

  DOI：

  10.1021/jm401382v

文献信息

• AZAINDOLE COMPOUNDS, SYNTHESIS THEREOF, AND METHODS OF USING THE SAME
  申请人：Global Alliance for TB Drug Development

  公开号：US20150025087A1

  公开（公告）日：2015-01-22

  The invention provides compounds of formula (I) and methods of treating a Mycobacterium infection or tuberculosis, or inhibiting DprE1 with the same.

  该发明提供了式（I）的化合物以及用于治疗结核分枝杆菌感染或肺结核，或者用于抑制DprE1的方法。
• Identification and optimisation of a pyrimidopyridone series of IRAK4 inhibitors
  作者：Iain A. Cumming、Sébastien L. Degorce、Anna Aagaard、Erin L. Braybrooke、Nichola L. Davies、Coura R. Diène、Andrew J. Eatherton、Hannah R. Felstead、Sam D. Groombridge、Eva M. Lenz、Yunxia Li、Youfeng Nai、Stuart Pearson、Graeme R. Robb、James S. Scott、Oliver R. Steward、Chengyan Wu、Yafeng Xue、Lanping Zhang、Yanxiu Zhang

  DOI：10.1016/j.bmc.2022.116729

  日期：2022.6

  large basic substituent to a 1-methylcyclopyl group. Subsequent optimisation, facilitated by X-ray crystal structures, allowed identification of preferred substituents at both the pyridone core and pyrazole. Subsequent combinations of optimal groups allowed control of lipophilicity and identification of potent and selective inhibitors of IRAK4 with better in vitro permeability and lower clearance.

  在本文中，我们报告了一系列作为 IRAK4 激酶抑制剂的嘧啶并吡啶酮的发现。从先前公开的 5-氮杂喹唑啉系列中，我们发现将吡啶环转换为N-取代的吡啶酮产生了一种新的铰链结合支架，它保留了对 IRAK4 的效力。重要的是，羰基的引入与 4-NH 建立了内部氢键，建立了构象锁并允许将大的碱性取代基截断为 1-甲基环基。随后的优化，由 X 射线晶体结构促进，允许在吡啶酮核和吡唑处鉴定优选的取代基。最佳组的后续组合允许控制亲脂性并鉴定具有更好体外渗透性和更低清除率的强效和选择性 IRAK4 抑制剂。
• Lead Optimization of 1,4-Azaindoles as Antimycobacterial Agents
  作者：Pravin S. Shirude、Radha K. Shandil、M. R. Manjunatha、Claire Sadler、Manoranjan Panda、Vijender Panduga、Jitendar Reddy、Ramanatha Saralaya、Robert Nanduri、Anisha Ambady、Sudha Ravishankar、Vasan K. Sambandamurthy、Vaishali Humnabadkar、Lalit K. Jena、Rudrapatna S. Suresh、Abhishek Srivastava、K. R. Prabhakar、James Whiteaker、Robert E. McLaughlin、Sreevalli Sharma、Christopher B. Cooper、Khisi Mdluli、Scott Butler、Pravin S. Iyer、Shridhar Narayanan、Monalisa Chatterji

  DOI：10.1021/jm500571f

  日期：2014.7.10

  In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.