2-氟-5-甲基苯肼盐酸盐 | 388080-67-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氟-5-甲基苯肼盐酸盐
• 英文名称: (2-fluoro-5-methyl-phenyl)hydrazine hydrochloride
• 英文别名: (2-Fluoro-5-methylphenyl)hydrazine hydrochloride；(2-fluoro-5-methylphenyl)hydrazine;hydrochloride
• CAS: 388080-67-9
• 化学式: C₇H₉FN₂*ClH
• mdl: MFCD09878859
• 分子量: 176.621
• InChiKey: SVKPTIJUJUSKTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  38
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-氟-5-甲基苯肼盐酸盐 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 (6-fluoro-9-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-[5-(trifluoromethyl)-1H-pyrazol-3-yl]methanone
  参考文献：
  名称：

  Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

  摘要：

  Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of gamma-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.

  DOI：

  10.1021/acs.jmedchem.0c01050
• 作为产物：
  描述：

  2-氟-5-甲基苯胺 在 盐酸 、 四氯化锡 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 24.0h， 以45%的产率得到2-氟-5-甲基苯肼盐酸盐
  参考文献：
  名称：

  Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

  摘要：

  Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of gamma-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.

  DOI：

  10.1021/acs.jmedchem.0c01050

文献信息

• Substituent effects on the isomerization of hydrazone switches driven by the intramolecular hydrogen bond
  作者：Chaocao Lu、Bu Htan、Shitao Fu、Chunmiao Ma、Quan Gan

  DOI：10.1016/j.tet.2019.06.022

  日期：2019.7

  In this work, the substituent effects on hydrogen bonding in one kind of hydrazone-based switch are revealed. The E/Z isomerization ratios of these hydrazones and their intramolecular hydrogen bond strengths in the Z form were evaluated using NMR technique. Linear correlations between these parameters and Hammett empirical values for substituent effects are explored as well.

  在这项工作中，揭示了一种基开关中取代基对氢键的影响。使用NMR技术评估这些的E / Z异构化比例及其在Z形式下的分子内氢键强度。还探讨了这些参数与Hammett经验值之间关于取代基效应的线性相关性。
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE LA FIBROSE KYSTIQUE
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2020012427A1

  公开（公告）日：2020-01-16

  The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising the compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular to modulate CFTR protein or ABC protein activities.

  本发明涉及式(Ia)的化合物或其药学上可接受的盐、水合物、溶剂合物、包合物、多形体、立体异构体。进一步披露了一种包含式(Ia)的化合物的药物组合物，以及利用式(Ib)的化合物，特别是用于调节CFTR蛋白或ABC蛋白活性。
• New Heterocyclic compounds for therapeutic use
  申请人：J.B. Chemicals & Pharmaceuticals Limited

  公开号：US20010047023A1

  公开（公告）日：2001-11-29

  A class of compounds particularly diaryl pyrazole of general formulas 1 and 2 where R and R′ represents alkyl, hydrogen, halogens, haloalkyl, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, hydroxyalkyl, alkylthio, alkylsulfinyl, alkylsulphonyl, N- alkylsulfamyl, N-arylsulfamyl, cyanoamido, amino, amidino, N-monoalkylamido, N-monoarylamido, N,N-dialkylamido, N-alkyl-N-arylamido, N, N-dialkylsulfamyl with the alkyl, or alkyl part of each such group containing 1-3 carbon atoms or mixtures thereof optionally their salts when they exist, and preparation thereof. The compounds of the present invention are antiinflammatory, antipyretic, antirheumatic, antiosteoarthritic agents with antibacterial activity. The particular class of compounds is given below (Formula 1 and Formula 2). 1

  一类化合物，特别是通式1和2的二芳基吡唑化合物，其中R和R′代表烷基、氢、卤素、卤代烷基、氰基、硝基、甲酰基、羧基、烷氧羰基、羧基烷基、烷氧羰基烷基、羟基烷基、烷基硫基、烷基亚砜基、N-烷基磺酰胺基、N-芳基磺酰胺基、氰基酰胺基、氨基、氨基甲酰胺基、N-烷基氨基甲酰胺基、N-芳基氨基甲酰胺基、N,N-二烷基氨基甲酰胺基、N-烷基-N-芳基氨基甲酰胺基、N,N-二烷基磺酰胺基，其中每个这样的基团的烷基或烷基部分含有1-3个碳原子，或它们的混合物，必要时存在时，以及它们的制备方法。本发明的化合物具有抗炎、退热、抗风湿、抗骨关节炎活性和抗菌活性。具体的化合物类别如下（通式1和通式2）。
• HETEROCYCLIC COMPOUNDS FOR THERAPEUTIC USE
  申请人：J.B. Chemicals & Pharmaceuticals Ltd.

  公开号：EP1377289A2

  公开（公告）日：2004-01-07
• EP1377289A4
  申请人：——

  公开号：EP1377289A4

  公开（公告）日：2008-09-10