N-hydroxy-3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzenecarboxamide imine | 153168-47-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-hydroxy-3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzenecarboxamide imine
• 英文别名: N-Hydroxy-3,5-dimethyl-4-[3-(3-methyl-5-isoxazolyl)propoxy]benzenecarboximidamide；N'-hydroxy-3,5-dimethyl-4-[3-(3-methyl-1,2-oxazol-5-yl)propoxy]benzenecarboximidamide
• CAS: 153168-47-9
• 化学式: C₁₆H₂₁N₃O₃
• 分子量: 303.361
• InChiKey: SOZGCLLJFRRECG-UHFFFAOYSA-N

物化性质

• 沸点：
  494.8±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-hydroxy-3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzenecarboxamide imine 在 lithium hexamethyldisilazane 、 三氯乙酸 作用下， 反应 97.92h， 生成 5-{3-[2,6-Dimethyl-4-(5-acetamido-1,2,4-oxadiazol-3-yl)phenoxy]-propyl}-3-methylisoxazole
  参考文献：
  名称：

  Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity

  摘要：

  A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC(80), the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.

  DOI：

  10.1021/jm00041a022
• 作为产物：
  描述：

  3,5-二甲基-4-羟基苯甲腈 在 盐酸羟胺 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 78.0h， 生成 N-hydroxy-3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzenecarboxamide imine
  参考文献：
  名称：

  Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity

  摘要：

  A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC(80), the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.

  DOI：

  10.1021/jm00041a022

文献信息

• 1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral
  申请人：Sterling Winthrop Inc.

  公开号：US05464848A1

  公开（公告）日：1995-11-07

  Compounds of the formula ##STR1## wherein: R.sub.1 is alkyl, alkoxy, hydroxy, cycloalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxy, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, carboxy, or cyanomethyl; Y is alkylene of 3 to 9 carbon atoms, R.sub.2 and R.sub.3 independently are hydrogen, alkyl, alkoxy, halo, cyano, trifluoromethyl and nitro; R.sub.4 is alkoxy, hydroxy, halomethyl, dihalomethyl, trihalomethyl, dihaloethyl, cycloalkyl, heterocyclyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, alkanecarbonyloxyalkyl, cyano, halo, thioalkyl, alkylthioalkyl, alkylthio, thio, 2,2,2-trifluoro-ethyl, (4-methylphenyl)sulfonyloxymethyl, N.dbd.Q or CON.dbd.Q, where N.dbd.Q is amino, alkylamino or dialkylamino; R.sub.5 is hydrogen or halo or alkyl.

  公式为##STR1##的化合物，其中：R.sub.1为烷基，烷氧基，羟基，环烷基，羟基烷基，烷氧基烷基，羟基烷氧基，烷基硫代烷基，烷基亚砜基烷基，烷基磺酰基烷基，氨基烷基，烷基氨基烷基，二烷基氨基烷基，烷氧羰基，羧基或氰甲基；Y为碳原子数为3至9的烷基，R.sub.2和R.sub.3独立地为氢，烷基，烷氧基，卤素，氰基，三氟甲基和硝基；R.sub.4为烷氧基，羟基，卤甲基，二卤甲基，三卤甲基，二卤乙基，环烷基，杂环烷基，烷氧羰基，羟基烷基，烷氧基烷基，烷基羧酸酯氧基烷基，氰基，卤素，硫代烷基，烷基硫代烷基，烷基硫，硫，2,2,2-三氟乙基，(4-甲基苯基)磺酰氧甲基，N.dbd.Q或CON.dbd.Q，其中N.dbd.Q为氨基，烷基氨基或二烷基氨基；R.sub.5为氢或卤素或烷基。
• Picornavirus Inhibitors: Trifluoromethyl Substitution Provides a Global Protective Effect against Hepatic Metabolism
  作者：Guy D. Diana、Patrick Rudewicz、Daniel C. Pevear、Theodore J. Nitz、Suzanne C. Aldous、David J. Aldous、David T. Robinson、Tandy Draper、Frank J. Dutko、Christopher Aldi、Guy Gendron、R. Christopher Oglesby、Deborah L. Volkots、Michael Reuman、Thomas R. Bailey、Richard Czerniak、Tracey Block、Robert Roland、James Oppermann

  DOI：10.1021/jm00008a014

  日期：1995.4.1

  Several modifications of the oxazoline ring of WIN 54954, a broad spectrum antipicornavirus compound, have been prepared in order to address the acid lability and metabolic instability of this compound. We have previously shown that the oxadiazole analogue 3 displayed comparable activity against a variety of rhinoviruses and appeared to be stable to acid. A monkey liver microsomal assay was developed to examine the metabolic stability in vitro of both compounds, and it was determined that WIN 54954 displayed 18 metabolic products while 3 was converted to 8 products. Two major products of 3 were determined by LC-MS/MS to be monohydroxylated at each of the terminal methyl groups. Replacement of the methyl on the isoxazole ring with a trifluoromethyl group, while preventing hydroxylation at this position, did not reduce the sensitivity of the molecule to microsomal metabolism at other sites. However, the (trifluoromethyl)oxadiazole 9 not only prevented hydroxylation at this position but also provided protection at the isoxazole end of the molecule, resulting in only two minor products to the extent of 4%. The major product was identified as the monohydroxylated compound 23. The global metabolic protective effect of trifluoromethyl group on the oxadiazole ring was further demonstrated by examining a variety of analogues including heterocyclic replacements of the isoxazole ring. In each case, the trifluoromethyl analogue displayed a protective effect when compared to the corresponding methyl analogue.
• 1,2,4-Oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents
  申请人：SANOFI

  公开号：EP0566199B1

  公开（公告）日：2000-03-01
• J. Med. Chem. 1995, 38, 1355-1371
  作者：

  DOI：——

  日期：——
• US5349068A
  申请人：——

  公开号：US5349068A

  公开（公告）日：1994-09-20