1-amino-3-fluoropyridin-1-ium 2,4,6-trimethylbenzenesulfonate | 886221-74-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-amino-3-fluoropyridin-1-ium 2,4,6-trimethylbenzenesulfonate
• 英文别名: 3-fluoro-1-aminopyridinium mesitylenesulfonate；1-amino-3-fluoropyridinium 2,4,6-trimethylbenzenesulfonate；1-Amino-3-fluoropyridin-1-ium 2,4,6-trimethylbenzenesulfonate；3-fluoropyridin-1-ium-1-amine;2,4,6-trimethylbenzenesulfonate
• CAS: 886221-74-5
• 化学式: C₅H₆FN₂*C₉H₁₁O₃S
• 分子量: 312.365
• InChiKey: ZEIJSUSYZPSKLE-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  95.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(tetrahydropyran-2-yloxy)-but-2-ynal 、 1-amino-3-fluoropyridin-1-ium 2,4,6-trimethylbenzenesulfonate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以13%的产率得到6-fluoro-2-(tetrahydropyran-2-yloxymethyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde
  参考文献：
  名称：

  Discovery of (1S,2R,3R)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors

  摘要：

  Aggrecanases, particularly aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5), are believed to be key enzymes involved in the articular cartilage breakdown that leads to osteoarthritis. Thus, aggrecanases are considered to be viable drug targets for the treatment of this debilitating disease. A cries of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates was discovered to be potent, highly selective, aid orally bioavailable aggrecanase inhibitors. These compounds have unique P1' groups comprising novel piperidine- or piperazin e-based heterocycles that are connected to a cyclopropane amino acid scaffold via a sulfamido linkage. These P1' groups are quite effective in imparting selectivity over other MMPs, and this selectivity was further increased by incorporation of a methyl substituent in the 2-position of the cyclopropane ring. In contrast to classical hydroxamate-based inhibitors that tend to lack metabolic stability, our aggrecanase inhibitors bear a carboxylate zinc-binding group and have good oral bioavailability. Lead compound 13b, characterized by the novel P1' portion of 1,2,3,4-tetrahydropyrido[3',4':4,5]imidazo [1,2-a]-pyridine ring, is a potent and selective aggrecanse inhibitor with excellent pharmacokinetic profiles.

  DOI：

  10.1021/jm101609j
• 作为产物：
  描述：

  O-(2,4,6-三甲基苯磺酰基)乙酰羟肟酸乙酯 在 高氯酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 1-amino-3-fluoropyridin-1-ium 2,4,6-trimethylbenzenesulfonate
  参考文献：
  名称：

  [EN] PYRIMIDINE INHIBITORS OF KINASE ACTIVITY
  [FR] INHIBITEURS PYRIMIDINES DE L'ACTIVITÉ KINASE

  摘要：

  本发明涉及式(I)的化合物或其药用可接受的盐或溶剂，其中G1、R2、R3、R4、R5、n、p、q、Ar1和Ar2在描述中有定义。本发明还涉及制备所述化合物的方法，以及包含所述化合物的组合物，用于抑制IGF-IR等激酶。

  公开号：

  WO2010138576A1

文献信息

• Heteroaryl imidazolone derivatives as jak inhibitors
  申请人：Almirall, S.A.

  公开号：EP2397482A1

  公开（公告）日：2011-12-21

  New heteroaryl imidazolone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  新的杂环基咪唑酮衍生物具有化学结构式(I)，公开了它们的制备方法，包括它们的制药组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。
• [EN] HETEROARYL IMIDAZOLONE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS D'HÉTÉROARYLE IMIDAZOLONE EN TANT QU'INHIBITEURS DE JAK
  申请人：ALMIRALL SA

  公开号：WO2011157397A1

  公开（公告）日：2011-12-22

  New heteroaryl imidazolone derivatives having the chemical structure of formula (I) disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  新的杂环芳基咪唑酮衍生物具有化学结构式（I）所示；以及它们的制备方法，包含它们的药物组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。
• [EN] IMIDAZO [1, 2 -A] PYRIDINE AND PYRAZOLO [1, 5 -A] PYRIDINE DERIVATIVES AS TRPV1 ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZO[1,2-A]PYRIDINE ET DE PYRAZOLO[1,5-A]PYRIDINE EN TANT QU'ANTAGONISTES DU TRPV1
  申请人：GLAXO GROUP LTD

  公开号：WO2012045729A1

  公开（公告）日：2012-04-12

  A compound of formula of formula (I) wherein A represents a single bond, a CH2 group or a CH (Me) group; X1 represents a hydrogen atom, a fluorine atom or a methyl group; X2 represents a hydrogen atom, a fluorine atom, a methyl group or a CH2OH group; X3 represents a hydrogen atom, a fluorine atom or a CH2OH group, and at least two of X1, X2 and X3 are hydrogen; Y represents a C atom and Z represents a N atom or Y represents an N atom and Z represents a C atom. R1 represents a halogen atom, a C1-4 alkyl group, a trifluoromethyl group or a trifluoromethoxy group, and R2 and R3 are each independently selected from a hydrogen atom, a halogen atom, a C1-4 alkyl group, a trifluoromethyl group or a trifluoromethoxy group. or a pharmaceutically acceptable salt or solvate thereof. salt or solvate thereof.

  化合物的化学式为（I），其中A代表一个单键，一个CH2基团或一个CH（Me）基团；X1代表一个氢原子，一个氟原子或一个甲基基团；X2代表一个氢原子，一个氟原子，一个甲基基团或一个CH2OH基团；X3代表一个氢原子，一个氟原子或一个CH2OH基团，且至少两个X1、X2和X3中有两个是氢；Y代表一个碳原子，Z代表一个氮原子，或Y代表一个氮原子，Z代表一个碳原子。R1代表一个卤素原子，一个C1-4烷基基团，一个三氟甲基基团或一个三氟甲氧基团，R2和R3分别独立选择自一个氢原子，一个卤素原子，一个C1-4烷基基团，一个三氟甲基基团或一个三氟甲氧基团，或其药用可接受的盐或溶剂。
• Regioselective Synthesis of Pyrazolo[1,5-<i>a</i>]pyridine via TEMPO-Mediated [3 + 2] Annulation–Aromatization of <i>N</i>-Aminopyridines and α,β-Unsaturated Compounds
  作者：Amu Wang、Ya-Zhou Liu、Zhongke Shen、Zeen Qiao、Xiaofeng Ma

  DOI：10.1021/acs.orglett.2c00035

  日期：2022.2.25

  A TEMPO-mediated [3 + 2] annulation–aromatization protocol for the preparation of pyrazolo[1,5-a]pyridines from N-aminopyridines and α,β-unsaturated compounds was developed. The procedure offered multisubstituted pyrazolo[1,5-a]pyridines in good to excellent yield with high and predictable regioselectivity. The modification of marketed drugs including Loratadine, Abiraterone, and Metochalcone, and

  开发了一种 TEMPO 介导的 [3 + 2] 环化-芳构化方案，用于从N-氨基吡啶和 α,β-不饱和化合物制备吡唑并[1,5- a ]吡啶。该方法提供了多取代的吡唑并[1,5- a ]吡啶，产率从良好到优异，具有高和可预测的区域选择性。展示了氯雷他定、阿比特龙和甲查耳酮等上市药物的改性，以及用于制备 Selpercatinib 的关键中间体的一锅三步克级规模合成。机理研究表明，TEMPO 既可用作路易斯酸，又可用作氧化剂。
• HETEROARYL IMIDAZOLONE DERIVATIVES AS JAK INHIBITORS
  申请人：Eastwood Paul Robert

  公开号：US20130089512A1

  公开（公告）日：2013-04-11

  New heteroaryl imidazolone derivatives having the chemical structure of formula (I) are disclosed, as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  本发明公开了具有化学结构式（I）的新杂环芳基咪唑酮衍生物，以及它们的制备方法、包含它们的制药组合物和它们作为Janus激酶（JAK）抑制剂在治疗中的应用。