4-<3-(5-methyl-1,2,4-oxadiazolyl)>-2,6-dimethylphenol | 156787-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-<3-(5-methyl-1,2,4-oxadiazolyl)>-2,6-dimethylphenol
• 英文别名: 2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazole-3-yl)-phenol；4-(5-methyl-1,2,4-oxadiazol-3-yl)-2,6-dimethylphenol；2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenol
• CAS: 156787-42-7
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: FKDWQPYZZBBCSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-<3-(5-methyl-1,2,4-oxadiazolyl)>-2,6-dimethylphenol 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 [5-[3-[2,6-Dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl]isoxazol-3-yl]methanol
  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：

  N,4-dihydroxy-3,5-dimethylbenzimidamide 在 吡啶 、 sodium hydroxide 、 水 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 4-<3-(5-methyl-1,2,4-oxadiazolyl)>-2,6-dimethylphenol
  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

• Therapeutic phenoxyalkylazoles and phenoxyalkylazines
  申请人：Sterling Winthrop Inc.

  公开号：US05552420A1

  公开（公告）日：1996-09-03

  Compounds of the formula ##STR1## wherein Azo is alkyltetrazolyl, oxadiazolyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, triazinyl, thiazolyl, isothiazolyl; Y is an alkylene bridge of 3-9 carbon atoms; R.sub.3 is alkoxycarbonyl, alkyltetrazolyl, phenyl or a heterocycle chosen from benzoxazolyl, benzathiazolyl, thiadiazolyl, imidazolyl, dihydroimidazolyl, oxazolyl, thiazolyl, oxadiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, furyl, triazolyl, tetrazolyl, thiophenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or substituted phenyl or substituted heterocyclyl is an effective antipicornaviral agents.

  式##STR1##中的化合物，其中Azo是烷基四唑基，噁二唑基，咪唑基，吡唑基，三唑基，噁唑基，三嗪基，噻唑基，异噻唑基；Y是3-9个碳原子的烷基桥；R.sub.3是烷氧羰基，烷基四唑基，苯基或从苯并噁唑基，苯并噻唑基，噻二唑基，咪唑基，二氢咪唑基，噁唑基，噻唑基，噁二唑基，吡唑基，异噁唑基，异噻唑基，呋喃基，三唑基，四唑基，噻吩基，吡啶基，嘧啶基，吡嗪基，吡啶并嘧啶基或取代苯基或取代杂环基是有效的抗小肠病毒药物。
• Therapeutic phenoxyalkylheterocycles
  申请人：Sanofi, S.A.

  公开号：US05618821A1

  公开（公告）日：1997-04-08

  Compounds of the formula ##STR1## wherein Q is chosen from the group consisting of pyridyl, pyrazyl, pyrimidyl, quinolyl, indolyl and 7-azaindolyl or any of these substituted with one or two substituents; Y is an alkylene bridge of 3-9 carbon atoms; R.sub.1 and R.sub.2 are each independently chosen from hydrogen, halo, alkyl, alkenyl, amino, alkylthio, hydroxy, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, nitro, carboxy, alkoxycarbonyl, dialkylaminoalkyl, alkylaminoalkyl, aminoalkyl, difluoromethyl, trifluoromethyl or cyano; R.sub.3 is alkoxycarbonyl, alkyltetrazolyl, substituted or unsubstituted phenyl or heterocyclyl, the N-oxide thereof, or a pharmaceutically acceptable acid addition salt thereof is an effective antipicornaviral agent.

  式##STR1##中的化合物，其中Q选择自吡啶基、吡唑基、嘧啶基、喹啉基、吲哚基和7-吡啶基中的一种或这些基中的一种或两种取代基; Y是3-9个碳原子的烷基桥; R.sub.1和R.sub.2分别独立地选择自氢、卤素、烷基、烯基、氨基、烷硫基、羟基、羟基烷基、烷氧基烷基、烷硫基烷基、烷基磺基烷基、烷氧基、硝基、羧基、烷氧羰基、二烷基氨基烷基、烷基氨基烷基、氨基烷基、二氟甲基、三氟甲基或氰基; R.sub.3是烷氧羰基、烷基四唑基、取代或未取代的苯基或杂环基，其N-氧化物，或其药用可接受的酸盐是一种有效的抗小肠病毒药剂。
• An Evaluation of the Antirhinoviral Activity of Acylfuran Replacements for 3-Methylisoxazoles. Are 2-Acetylfurans Bioisosteres for 3-Methylisoxazoles?
  作者：Thomas R. Bailey、Guy D. Diana、John P. Mallamo、Niranjan Vescio、Tandy L. Draper、Philip M. Carabateas、Melody A. Long、Vincent L. Giranda、Frank J. Dutko、Daniel C. Pevear

  DOI：10.1021/jm00050a014

  日期：1994.11

  probe of the 3-methylisoxazole portion of our broad-spectrum antipicornaviral series, a panel of 2-acetylfuran analogues was prepared as replacements for the 3-methylisoxazole ring. Comparison of the two series showed remarkable similarity in potency, spectrum of activity, logP, and electrostatic parameters. X-ray studies of 21b bound to human rhinovirus-14 showed that the 2-acetyl group adopted a syn conformation

  作为我们广谱抗picornaviral系列中3-甲基异恶唑部分的探针，制备了一组2-乙酰基呋喃类似物来替代3-甲基异恶唑环。两个系列的比较显示出在功效，活性谱，logP和静电参数方面的显着相似性。对与人鼻病毒14结合的21b的X射线研究表明，2-乙酰基采用了syn构象，而羰基氧则以与异恶唑的氮几乎相同的方式充当了ASN219的氢键受体。2-甲基呋喃和2-甲酰基呋喃类似物的抗病毒活性降低证实了顺式构象和氢键能力的重要性。从该研究的结果，很明显，syn-2-乙酰基呋喃环起3-甲基异恶唑的生物等排体的作用。
• Thiadiazoles and antipicornaviral compositions
  申请人：Sterling Winthrop Inc.

  公开号：US05453433A1

  公开（公告）日：1995-09-26

  Compounds of the formula; ##STR1## wherein: Thi is thiadiazolyl or substituted thiadiazolyl; Y is alkylene bridge of 3-9 carbon atoms; R.sub.1 and R.sub.2 are each independently chosen from hydrogen, halo, alkyl, alkenyl, amino, alkylthio, hydroxy, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfinyl alkyl, alkylsulfonylalkyl, alkoxy, nitro, carboxy, alkoxycarbonyl, dialkylaminoalkyl, alkylaminoalkyl, aminoalkyl, difluoromethyl, trifluoromethyl, or cyano; R.sub.3 is alkoxycarbonyl, phenyl, alkyltetrazolyl, or heterocyclyl; or a pharmaceutically acceptable salt thereof are effective antipicornaviral agents.

  该公式化合物的化合物; ## STR1 ##其中：Thi是噻二唑基或取代的噻二唑基；Y是3-9个碳原子的烷基桥；R.sub.1和R.sub.2分别选择自氢、卤素、烷基、烯基、氨基、烷基硫醚、羟基、羟基烷基、烷氧基烷基、烷基硫醚基、烷基磺醚基、烷氧基、硝基、羧基、烷氧羰基、二烷基氨基烷基、烷基氨基烷基、氨基烷基、二氟甲基、三氟甲基或氰基；R.sub.3是烷氧羰基、苯基、烷基四唑基或杂环基；或其在药理学上可接受的盐是有效的抗小RNA病毒药物。
• OXADIAZOLE COMPOUND AND PREPARATION METHOD THEREOF, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：SHANGHAI JIAO TONG UNIVERSITY

  公开号：US20140350026A1

  公开（公告）日：2014-11-27

  The present invention provides an anti-Coxsackie virus oxadiazole compound as represented by formula (I), or the pharmaceutically acceptable salt thereof, a preparation method, a pharmaceutical composition, and use thereof, wherein R is CH3 or CF3; R′ and R″ are respectively H, alkyl or halogen; A is O or S; n is a number from 1 to 6; X is O, S or NH; Y is alkyl, unsubstituted cycloalkyl, mono-substituted cycloalkyl, disubstituted cycloalkyl, poly-substituted cycloalkyl, unsubstituted aryl, mono-substituted aryl, disubstituted aryl, poly-substituted aryl, unsubstituted 5-6 membered heterocyclyl, mono-substituted 5-6 membered heterocyclyl, disubstituted 5-6 membered heterocyclyl, or poly-substituted 5-6 membered heterocyclyl. Compared to prior art, the oxadiazole compound of the present invention has excellent anti-Coxsackie virus activity, lower toxicity and high safety.

  本发明提供了一种抗柯萨奇病毒的噁二唑化合物，其化学式为（I）或其药学上可接受的盐，以及其制备方法、制药组合物和用途。其中，R为CH3或CF3；R'和R"分别为H、烷基或卤素；A为O或S；n为1至6的数字；X为O、S或NH；Y为烷基、未取代的环烷基、单取代的环烷基、双取代的环烷基、多取代的环烷基、未取代的芳基、单取代的芳基、双取代的芳基、多取代的芳基、未取代的5-6元杂环基、单取代的5-6元杂环基、双取代的5-6元杂环基或多取代的5-6元杂环基。与现有技术相比，本发明的噁二唑化合物具有优异的抗柯萨奇病毒活性，毒性较低，安全性高。