[1,2,4]Triazolo[1,5-a]pyridin-8-ol | 86467-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: [1,2,4]Triazolo[1,5-a]pyridin-8-ol
• CAS: 86467-41-6
• 化学式: C₆H₅N₃O
• 分子量: 135.125
• InChiKey: NHGGFXCWPNQTLS-UHFFFAOYSA-N

物化性质

• 熔点：
  197-201 °C
• 溶解度：
  氯仿（微溶，超声处理），DMSO（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1,2,4]Triazolo[1,5-a]pyridin-8-ol 在 三甲基铝 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.25h， 生成 8-<<1-(4,5-dihydro-1H-imidazol-2-yl)ethyl>oxy><1,2,4>triazolo<1,5-a>pyridine
  参考文献：
  名称：

  Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines

  摘要：

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.

  DOI：

  10.1021/jm00164a024
• 作为产物：
  描述：

  2-氨基-3-苄氧基吡啶 在 palladium on activated charcoal 吡啶 、 氢气 、 hydroxylamine-O-sulfonic acid 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 38.0h， 生成 [1,2,4]Triazolo[1,5-a]pyridin-8-ol
  参考文献：
  名称：

  Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines

  摘要：

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.

  DOI：

  10.1021/jm00164a024

文献信息

• 2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS
  申请人：Aicher Thomas Daniel

  公开号：US20100105659A1

  公开（公告）日：2010-04-29

  Provided are compounds that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.

  提供了一些化合物，这些化合物在治疗和/或预防由葡萄糖激酶活性不足引起的疾病中非常有用，例如糖尿病。同时提供了治疗或预防由葡萄糖激酶活性不足或可以通过激活葡萄糖激酶治疗的疾病和疾病的方法。
• STANOVNIK, B.;PODERGAJS, S.;TISLER, M.;VERCEK, B., VESTN. SLOV. KEM. DRUST., 1983, 30, N 1, 39-49
  作者：STANOVNIK, B.、PODERGAJS, S.、TISLER, M.、VERCEK, B.

  DOI：——

  日期：——
• US8362037B2
  申请人：——

  公开号：US8362037B2

  公开（公告）日：2013-01-29
• [EN] 2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS<br/>[FR] ANALOGUES DE LA 2-AMINOPYRIDINE COMME ACTIVATEURS DE LA GLUCOKINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2008118718A2

  公开（公告）日：2008-10-02

  [EN] Provided are compounds that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.
  [FR] La présente invention concerne des composés qui sont utiles dans le traitement et/ou la prévention de maladies provoquées par des niveaux déficients de l'activité de la glucokinase, telles que le diabète sucré. L'invention concerne également des procédés de traitement ou de prévention de maladies et de troubles caractérisés par une sous-activité de la glucokinase ou qui peuvent être traités en activant la glucokinase.
• Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines
  作者：Alan E. Moormann、Barnett S. Pitzele、P. H. Jones、Gary W. Gullikson、David Albin、Stella S. Yu、Robert G. Bianchi、Elizabeth L. Sanguinetti、Barbara Rubin

  DOI：10.1021/jm00164a024

  日期：1990.2

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.