4-氟-3-甲基异硫氰酸苯酯 | 351003-66-2

• 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: 4-氟-3-甲基异硫氰酸苯酯
• 中文别名: 4-氟-3-甲苯基异硫氰酸酯
• 英文名称: 4-fluoro-3-methylphenyl isothiocyanate
• 英文别名: 1-fluoro-4-isothiocyanato-2-methylbenzene
• CAS: 351003-66-2
• 化学式: C₈H₆FNS
• mdl: MFCD00046806
• 分子量: 167.207
• InChiKey: UNHFKKWNCOJAKR-UHFFFAOYSA-N

物化性质

• 沸点：
  215 °C(lit.)
• 密度：
  1.19

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  4-氟-3-甲基异硫氰酸苯酯 、 2-amino-6-(4-chloro-3-methoxyphenyl)cyclohexan-1-one hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-(3-(4-chloro-3-methoxyphenyl)-2-oxocyclohexyl)-3-(4-fluoro-3-methylphenyl)thiourea
  参考文献：
  名称：

  Discovery of Orally Efficacious Tetrahydrobenzimidazoles as TGR5 Agonists for Type 2 Diabetes

  摘要：

  We have discovered a novel series of tetrahydrobenzimidazoles 3 as TGR5 agonists. Initial structure activity relationship studies with an assay that measured cAMP levels in murine enteroendocrine cells (STC-1 cells) led to the discovery of potent agonists with submicromolar EC50 values for mTGRS. Subsequent optimization through methylation of the 7-position of the core tetrahydrobenzimidazole ring resulted in the identification of potent agonists for both mTGR5 and hTGRS (human enteroendocrine NCI-H716 cells). While the lead compounds displayed low to moderate exposure after oral dosing, they significantly reduced blood glucose levels in C57 BL/6 mice at 30 mg/kg and induced a 13-22% reduction in the area under the blood glucose curve (AUC)(0-120 min) in oral glucose tolerance tests (OGTT).

  DOI：

  10.1021/acsmedchemlett.7b00116

文献信息

• [EN] FUSED BICYCLIC SULFAMOYL DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B<br/>[FR] DÉRIVÉS DE SULFAMOYLE BICYCLIQUES FUSIONNÉS ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS POUR LE TRAITEMENT DE L'HÉPATITE B
  申请人：JANSSEN R & D IRELAND

  公开号：WO2014033167A1

  公开（公告）日：2014-03-06

  Inhibitors of HBV replication of Formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein A-E, R1, R2, R3 and R5, have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

  公式（I）的HBV复制抑制剂包括立体化学同分异构体形式，以及其盐、水合物、溶剂合物，其中A-E、R1、R2、R3和R5的含义如本文所定义。本发明还涉及制备所述化合物的方法、含有它们的药物组合物以及它们在HBV治疗中的使用，单独或与其他HBV抑制剂结合使用。
• [EN] 2-CYANO-3-CYCLOPROPYL-3-HYDROXY-N-ARYL-THIOACRYLAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE 2-CYANO-3-CYCLOPROPYL-3-HYDROXY-N-ARYL-THIOACRYLAMIDE
  申请人：ALGIAX PHARMACEUTICALS GMBH

  公开号：WO2015140081A1

  公开（公告）日：2015-09-24

  A compound of the formula (I) or a tautomeric isoform thereof wherein R1 is selected from the group consisting of halogen, nitro, lower alkyl sulfonyl, cyano, trifluromethyl lower alkyl, lower alkoxy, lower alkoxycarbonyl, carboxy, lower alkyl aminosulfonyl, perfluoro lower alkyl, lower alkylthio, hydroxy lower alkyl, alkoxy lower alkyl, lower alkylthio lower alkyl, lower alkylsulfinyl lower alkyl, lower alkylsulfonyl lower alkyl, lower alkylsulfinyl, lower alkanoyl, aroyl, aryl, aryloxy and R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, alkylthio, and alkylcarbonyl, and their non-toxic, pharmaceutically acceptable base addition salts or pro-drugs thereof. The compounds of the invention are useful in the treatment of nervous system diseases and disorders, which are responsive to modulation of the GABAA receptor complex.

  该化合物的结构式（I）或其互变异构体，其中R1被选自卤素、硝基、较低烷基磺酰基、氰基、三氟甲基较低烷基、较低烷氧基、较低烷氧羰基、羧基、较低烷基氨基磺酰基、全氟较低烷基、较低烷基硫基、羟基较低烷基、烷氧基较低烷基、较低烷硫基较低烷基、较低烷基亚砜基较低烷基、较低烷基砜基较低烷基、较低烷基亚砜基、较低烷酰基、芳酰基、芳基、芳氧基以及R2被选自氢、烷基、烷氧基、烷硫基和烷羰基的群组，以及它们的非毒性、药学上可接受的碱加盐或前药。该发明的化合物在治疗对GABAA受体复合物调节敏感的神经系统疾病和障碍方面具有用处。
• Tetrahydro-benzoimidazolyl modulators of TGR5
  申请人：Janssen Pharmaceutica NV

  公开号：US10077241B2

  公开（公告）日：2018-09-18

  The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, R6, R7, R8, X, Z1 and Z2 are defined in the specification.

  本发明包括式（I）化合物。 其中 R1、R2、R3、R4、R5、R6、R7、R8、X、Z1 和 Z2 的定义见说明书。
• 2-cyano-3-cyclopropyl-3-hydroxy-N-aryl-thioacrylamide derivatives
  申请人：Algiax Pharmaceuticals GmbH

  公开号：US10472324B2

  公开（公告）日：2019-11-12

  A compound of the formula (I) or a tautomeric isoform thereof wherein R1 is selected from the group consisting of halogen, nitro, lower alkyl sulfonyl, cyano, trifluromethyl lower alkyl, lower alkoxy, lower alkoxycarbonyl, carboxy, lower alkyl aminosulfonyl, perfluoro lower alkyl, lower alkylthio, hydroxy lower alkyl, alkoxy lower alkyl, lower alkylthio lower alkyl, lower alkylsulfinyl lower alkyl, lower alkylsulfonyl lower alkyl, lower alkylsulfonyl, lower alkanoyl, aroyl, aryl, aryloxy and R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, alkylthio, and alkylcarbonyl, and their non-toxic, pharmaceutically acceptable base addition salts or pro-drugs thereof. The compounds of the invention are useful in the treatment of nervous system diseases and disorders, which are responsive to modulation of the GABAA receptor complex.

  式(I)化合物或其同分异构体，其中 R1 选自由卤素、硝基、低级烷基磺酰基、氰基、三氟甲基低级烷基、低级烷氧基、低级烷氧羰基、羧基、低级烷基氨基磺酰基、全氟低级烷基、低级烷硫基、羟基低级烷基、烷氧基低级烷基、烷氧基低级烷基、低级烷硫基低级烷基、低级烷基亚磺酰基、低级烷基磺酰基、低级烷酰胺酰基、低级烷酰基、aroyl、aroyl、aroyl、aroyl、R2选自由氢、烷基、烷氧基、烷硫基和烷羰基组成的组，以及它们的无毒、药学上可接受的碱加成盐或原药。本发明的化合物可用于治疗对 GABAA 受体复合物的调节有反应的神经系统疾病和失调。
• FUSED BICYCLIC SULFAMOYL DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B
  申请人：Janssen Sciences Ireland UC

  公开号：EP2890683A1

  公开（公告）日：2015-07-08