5-methyl-N-[4-(methylthio)phenyl]-2-pyridinecarboximidamide | 177662-56-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-methyl-N-[4-(methylthio)phenyl]-2-pyridinecarboximidamide
• 英文别名: 5-methyl-N'-(4-methylsulfanylphenyl)pyridine-2-carboximidamide
• CAS: 177662-56-5
• 化学式: C₁₄H₁₅N₃S
• 分子量: 257.359
• InChiKey: NQEKOMMAPSFBIS-UHFFFAOYSA-N

物化性质

• 沸点：
  399.8±52.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methyl-N-[4-(methylthio)phenyl]-2-pyridinecarboximidamide 在 碳酸氢钠 、 对甲苯磺酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 8.5h， 生成 5-methyl-2-[1-[4-(methylthio)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine
  参考文献：
  名称：

  Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents

  摘要：

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

  DOI：

  10.1021/jm0000719
• 作为产物：
  描述：

  2-氟-5-甲基吡啶 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 5-methyl-N-[4-(methylthio)phenyl]-2-pyridinecarboximidamide
  参考文献：
  名称：

  Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents

  摘要：

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

  DOI：

  10.1021/jm0000719

文献信息

• Heterocyclo-substituted imidazoles for the treatment of inflammation
  申请人：Khanna K. Ish

  公开号：US20050096368A1

  公开（公告）日：2005-05-05

  A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (V), wherein R 3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy. aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R 4 is a radical selected from hydrido, alkyl and halo; and wherein R 13 and R 14 are independently selected from aryl and heterocyclo, wherein R 13 and R 14 are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R 13 and R 14 is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

  描述了一类咪唑基化合物用于治疗炎症。特别感兴趣的化合物由公式（V）定义，其中R3是从氢基，烷基，卤代烷基，芳基烷基，杂环烷基，杂环芳基烷基，酰基，氰基，烷氧基，烷硫基，烷硫基烷基，烷基磺酰基，环烷硫基，环烷硫基烷基，环烷磺酰基，环烷磺酰基烷基，卤代烷基磺酰基，芳基磺酰基，卤代基，羟基烷基，烷氧基烷基，烷基羧酰基，芳基羧酰基，芳基烷基羧酰基，杂环羧酰基，氰基烷基，氨基烷基，烷基氨基烷基，N-芳基氨基烷基，N-烷基-N-芳基氨基烷基，羧基烷基，烷氧基羧酰基烷基，烷氧基羧酰基，卤代烷基羧酰基，羧基，氨基羧酰基，烷基氨基羧酰基，杂环芳基烷氧基烷基，杂环芳基氧基烷基，杂环芳基硫基烷基，芳基硫醇基烷基，芳基氧基烷基，芳基硫醇基，芳基氧基。芳基烷硫基烷基，芳基烷氧基烷基，芳基和杂环芳基;其中R4是从氢基，烷基和卤代基中选择的基团;并且R13和R14分别从芳基和杂环芳基中选择，其中R13和R14在可取代位置上可以选择一个或多个基团独立地选择，包括烷基磺酰基，氨基磺酰基，卤代基，烷硫基，烷基，氰基，羧基，烷氧基羧酰基，卤代烷基，羟基，烷氧基，羟基烷基，烷氧基烷基，卤代烷氧基，氨基，烷基氨基，芳基氨基和硝基; 提供至少一个R13和R14被烷基磺酰基或氨基磺酰基取代的芳基，或其药学上可接受的盐。
• A process for the preparation of 4-[2-(aryl or heterocyclo)-1H-imidazol-1-yl]benzenesulfonamides
  申请人：G.D. Searle & Co.

  公开号：EP1193265A2

  公开（公告）日：2002-04-03

  A process to make a compound of the formula or a pharmaceutically acceptable salt thereof is disclosed wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkaxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R4 is a radical selected from hydrido, alkyl and halo; and wherein R2 is selected from aryl and heterocyclo, wherein R2 is optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro;    said method comprising the steps of forming a (protected sulfonyl)benzenamine, treating said (protected sulfonyl)benzenamine first with a base and then with a nitrile to form an amidine, treating said amidine with a haloketone derivative in the presence of a base to form a hydroxyimidazole, forming a (protected sulfonylphenyl) imidazole by dehydrating said hydroxyimidazole, and forming said compounds by deprotecting said (protected sulfonylphenyl)imidazole.

  本发明公开了一种制备式 或其药学上可接受的盐的工艺。 其中 R3 是选自氢基、烷基、卤代烷基、芳基、杂环烷基、杂芳基、酰基、氰基、烷氧基、烷硫基、烷硫基、烷基磺酰基、环烷硫基、环烷硫基、环烷基磺酰基、环烷基磺酰基、卤代烷基磺酰基、芳基磺酰基、卤代烷基磺酰基、卤代芳基磺酰基、卤代芳基磺酰基、环烷基磺酰基、卤代烷基磺酰基、芳基磺酰基、卤代、羟基烷基、烷氧基烷基、烷基羰基、芳基羰基、芳基羰基、杂环羰基、氰基烷基、氨基烷基、烷基氨基烷基、N-芳基氨基烷基、N-烷基-N-芳基氨基烷基、羧基、烷氧基羰基、烷氧羰基、卤代烷基羰基、羧基、氨基羰基、烷基氨基羰基、烷基氨基羰基烷基、杂芳基烷氧基烷基、杂芳氧基烷基、杂芳硫基烷基、杂芳基硫代烷基、杂芳基硫代烷基、杂芳基氧基烷基、杂芳基硫代烷基、芳基硫代烷基、芳基氧基烷基、芳基硫代烷基、芳基氧基烷基、芳基硫代烷基、芳基烷氧基烷基、芳基和杂芳基；其中 R4 是选自氢基、烷基和卤代的基团；以及 其中 R2 选自芳基和杂环基，其中 R2 在可取代的位置上任选被一个或多个独立选自烷基磺酰基、氨基磺酰基、卤代基、烷硫基、烷基、氰基、羧基、烷氧基羰基、卤代烷基、羟基、烷氧基、羟基烷基、烷氧基烷基、卤代烷氧基、氨基、烷基氨基、芳基氨基和硝基的基团取代； 所述方法包括以下步骤：形成(受保护的磺酰基)苯胺，首先用碱处理所述(受保护的磺酰基)苯胺，然后用腈处理以形成脒，在碱存在下用卤代酮衍生物处理所述脒以形成羟基咪唑，通过使所述羟基咪唑脱水形成(受保护的磺酰基苯基)咪唑，以及通过对所述(受保护的磺酰基苯基)咪唑进行脱保护形成所述化合物。
• A process for the preparation of 4-¬2-(aryl or heterocyclo)-1H-imidazol-1-yl|benzenesulfonamides
  申请人：G.D. Searle LLC

  公开号：EP1193265B1

  公开（公告）日：2006-11-29
• 1,2-SUBSTITUTED IMIDAZOLYL COMPOUNDS FOR THE TREATMENT OF INFLAMMATION
  申请人：G.D. SEARLE & CO.

  公开号：EP0772600B1

  公开（公告）日：2002-09-18
• HETEROCYCLO-SUBSTITUTED IMIDAZOLES FOR THE TREATMENT OF INFLAMMATION
  申请人：G.D. SEARLE & CO.

  公开号：EP0880504B1

  公开（公告）日：2003-04-02