2,6-二甲基-4-(2-甲基-1H-四唑-5-亚基)环己-2,5-二烯-1-酮 | 152665-33-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2,6-二甲基-4-(2-甲基-1H-四唑-5-亚基)环己-2,5-二烯-1-酮
• 英文名称: 2-methyl-5-(3,5-dimethyl-4-hydroxyphenyl)-2H-tetrazole
• 英文别名: 2,6-dimethyl-4-<5-(2-methyl-2H-tetrazolyl)>phenol；2,6-dimethyl-4-<5-(2-methyl-2H-tetrazolyl)>phenyl；2-methyl-(4-hydroxy-3,5-dimethylphenyl)-2H-tetrazole；2-methyl-5-(3,5-dimethyl-4-hydroxyphenyl)tetrazole；4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenol；2-methyl-5-(4-hydroxy-3,5-dimethylphenyl)-2H-tetrazole；2,6-Dimethyl-4-(2-methyltetrazol-5-yl)phenol
• CAS: 152665-33-3
• 化学式: C₁₀H₁₂N₄O
• 分子量: 204.231
• InChiKey: RYBFPEHWIREKRA-UHFFFAOYSA-N

物化性质

• 沸点：
  405.9±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,6-二甲基-4-(2-甲基-1H-四唑-5-亚基)环己-2,5-二烯-1-酮 在 lithium aluminium tetrahydride 、 溴 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 30.67h， 生成 5-<4-<<3-<3-(bromomethyl)-5-isoxazolyl>propyl>oxy>-3,5-dimethylphenyl>-2-methyl-2-H-tetrazole
  参考文献：
  名称：

  Antipicornavirus activity of tetrazole analogs related to disoxaril

  摘要：

  A series of tetrazole analogues of Win 54954, a broad-spectrum antipicornavirus compound, has been synthesized to address the acid lability of the oxazoline ring of this series of compounds. The results of X-ray crystallography studies of several members of the oxazoline series bound to human rhinovirus type IA and 14 have been used to design compounds in the tetrazole series with a broad spectrum of activity. Compound 16b, which has a three-carbon linkage between the isoxazole and phenyl rings and a propyl chain extending from the isoxazole ring, exhibiting an MIC80 for 15 rhinovirus serotypes of 0.20 muM as compared to 0.40 muM for Win 54954. X-ray studies of 16b bound to human rhinovirus-14 show that the propyl side chain extends into a pore in the binding site with the possibility of hydrophobic interactions with a pocket formed by Leu106 and a portion of Ser107.

  DOI：

  10.1021/jm00074a004
• 作为产物：
  描述：

  3,5-二甲基-4-甲氧基苯甲腈 在 sodium azide 、 三溴化硼 、 potassium carbonate 、 氯化铵 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.0h， 生成 2,6-二甲基-4-(2-甲基-1H-四唑-5-亚基)环己-2,5-二烯-1-酮
  参考文献：
  名称：

  Antipicornavirus activity of tetrazole analogs related to disoxaril

  摘要：

  A series of tetrazole analogues of Win 54954, a broad-spectrum antipicornavirus compound, has been synthesized to address the acid lability of the oxazoline ring of this series of compounds. The results of X-ray crystallography studies of several members of the oxazoline series bound to human rhinovirus type IA and 14 have been used to design compounds in the tetrazole series with a broad spectrum of activity. Compound 16b, which has a three-carbon linkage between the isoxazole and phenyl rings and a propyl chain extending from the isoxazole ring, exhibiting an MIC80 for 15 rhinovirus serotypes of 0.20 muM as compared to 0.40 muM for Win 54954. X-ray studies of 16b bound to human rhinovirus-14 show that the propyl side chain extends into a pore in the binding site with the possibility of hydrophobic interactions with a pocket formed by Leu106 and a portion of Ser107.

  DOI：

  10.1021/jm00074a004

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。
• Phenoxy- and phenoxyalkyl-piperidines as antiviral agents
  申请人：Sterling Winthrop Inc.

  公开号：US05364865A1

  公开（公告）日：1994-11-15

  Compounds of the formula ##STR1## wherein R.sub.1 is selected from ##STR2## Y is a bond or lower alkylene; R.sub.2 and R.sub.3 are independently hydrogen, lower-alkyl or halogen; R.sub.4 is ##STR3## R.sub.5 is hydrogen, lower-alkyl or halogen; R.sub.6 is hydrogen, lower-alkyl or halogen; R.sub.7 is hydrogen or lower-alkyl; R.sub.8 is hydrogen, lower-alkyl, or trifluoromethyl; R.sub.9 is lower-alkyl; R.sub.10 is lower-alkyl, trifluoromethyl or difluoromethyl; or pharmaceutically acceptable acid addition salts thereof are useful as antiviral agents.

  式为##STR1##的化合物，其中R.sub.1从##STR2##中选择；Y为键或较低的烷基；R.sub.2和R.sub.3独立地为氢、较低烷基或卤素；R.sub.4为##STR3##；R.sub.5为氢、较低烷基或卤素；R.sub.6为氢、较低烷基或卤素；R.sub.7为氢或较低烷基；R.sub.8为氢、较低烷基或三氟甲基；R.sub.9为较低烷基；R.sub.10为较低烷基、三氟甲基或二氟甲基；或其药用可接受酸盐作为抗病毒剂有用。
• 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。
• Therapeutic phenoxyalklpyridazines and intermediates therefor
  申请人：Sterling Winthrop Inc.

  公开号：US05514679A1

  公开（公告）日：1996-05-07

  Compounds of the formula ##STR1## wherein: R.sub.1 and R.sub.2 are independently hydrogen, halo, alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, hydroxyhaloalkyl, alkoxyalkyl, alkylthioalkynyl, hydroxyalkoxy, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, carboxy or cyanomethyl, nitro, difluoromethyl, trifluoromethyl or cyano; Y is alkylene of 3 to 9 carbon atoms; R.sub.3 and R.sub.4 are independently hydrogen, alkyl, alkoxy, hydroxy, cycloalkyl, hydroxyalkyl, hydroxyhaloalkyl, alkoxyalkyl, hydroxyalkoxy, alkylthioalkyl, alkanoyl, alkanoyloxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, carboxy, cyanomethyl, fluoroalkyl, cyano, phenyl, alkynyl, alkene, or halo; R.sub.5 is alkoxycarbonyl, alkyltetrazolyl, phenyl or a heterocycle; or a pharmaceutically acceptable acid addition salts thereof; N-oxides thereof, are useful as antipirconaviral agents.

  式为##STR1##的化合物，其中：R.sub.1和R.sub.2独立地是氢、卤素、烷基、烯基、烷氧基、羟基、羟基烷基、羟基卤代烷基、烷氧基烷基、烷硫烯基、羟基烷氧基、烷硫基烷基、烷基磺酰基烷基、烷基磺基烷基、氨基、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、硝基、二氟甲基、三氟甲基或氰基；Y为3至9个碳原子的烷基；R.sub.3和R.sub.4独立地是氢、烷基、烷氧基、羟基、环烷基、羟基烷基、羟基卤代烷基、烷氧基烷基、羟基烷氧基、烷硫基烷基、烷酰基、烷酰氧基、烷基磺酰基烷基、烷基磺基烷基、氨基烷基、烷基氨基烷基、二烷基氨基烷基、烷氧羰基、羧基、氰甲基、氟烷基、氰基、苯基、炔基、烯烃或卤素；R.sub.5为烷氧羰基、烷基四唑基、苯基或杂环；或其药学上可接受的酸盐；其N-氧化物可用作抗逆转录病毒药物。
• Therapeutic phenoxyalkylpyridazines and intermediates therefor
  申请人：Sanofi, S.A.

  公开号：US05665763A1

  公开（公告）日：1997-09-09

  Compounds of the formula ##STR1## wherein: R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification, Y is alkylene of 3 to 9 carbon atoms, R.sub.5 is alkoxycarbonyl, alkyltetrazolyl, phenyl or a heterocycle chosen from benzoxazolyl, benzathiazolyl, thiadiazolyl, imidazolyl, dihydroimidazolyl, oxazolyl, thiazolyl, oxadiazolyl, pyrazolyl, oxazolinyl, isoxazolyl, isothiazolyl, furyl, triazolyl, thiophenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or any of the above substituted with alkyl, alkoxyalkyl, cycloalkyl, halo alkyl, hydroxyalkyl, alkoxy, hydroxy, halo, furyl, thienyl, fluoroalkyl; or a pharmaceutically acceptable acid addition salts thereof; N-oxides thereof, are useful as antipirconaviral agents.

  式子为##STR1##的化合物，其中：R.sub.1、R.sub.2、R.sub.3和R.sub.4如规范中所定义，Y为3至9个碳原子的烷基，R.sub.5为烷氧羰基，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，噁唑啉基，异噁唑基，异噻唑基，呋喃基，三唑基，噻吩基，氟烷基取代的上述任何一个杂环；或其药学上可接受的酸盐；其N-氧化物，可用作抗病毒药剂。