4-(2-cyanoethyl)-2,6-dimethylphenol | 58471-30-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-(2-cyanoethyl)-2,6-dimethylphenol
• 英文别名: 3-(4-hydroxy-3,5-dimethylphenyl)propanenitrile；3-(3,5-Dimethyl-4-hydroxyphenyl)propionitrile
• CAS: 58471-30-0
• 化学式: C₁₁H₁₃NO
• 分子量: 175.23
• InChiKey: VYZAEOZMCHPNLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-cyanoethyl)-2,6-dimethylphenol 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 4-carboxy-5-[4''-(2-cyanoethyl)-2'',6''-dimethylphenoxy]-N¹-(4'-cyanophenyl)-2-nitroaniline
  参考文献：
  名称：

  Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus

  摘要：

  Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R-1 group might provide greater efficacy against the E138K mutant.

  DOI：

  10.1021/acs.jmedchem.5b01827
• 作为产物：
  描述：

  3,5-二甲基-4-羟基苯甲醛 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 7.0h， 生成 4-(2-cyanoethyl)-2,6-dimethylphenol
  参考文献：
  名称：

  Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus

  摘要：

  Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). Promising new compounds were then assessed for physicochemical and associated pharmaceutical properties, including aqueous solubility, log P value, and metabolic stability, as well as predicted lipophilic parameters of ligand efficiency, ligand lipophilic efficiency, and ligand efficiency-dependent lipophilicity indices, which are associated with ADME property profiles. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R-1 group might provide greater efficacy against the E138K mutant.

  DOI：

  10.1021/acs.jmedchem.5b01827

文献信息

• [EN] HIV INHIBITING 1,2,4-TRIAZInONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 1,2,4-TRIAZINONE INHIBITEURS DU VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006015985A1

  公开（公告）日：2006-02-16

  The present invention relates to HIV replication inhibitors of formula (I) a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein ring A and ring B represent phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl; n and m are 1 to 4; R1 represents hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxy C1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl; their use as a medicine, their use for the manufacture of a medicament for the treatment or the prevention of HIV infection; their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及公式(I)的HIV复制抑制剂，其中N-氧化物，药学上可接受的加盐物，季铵盐或其立体化学异构体形式，其中环A和环B代表苯基，吡啶基，吡啶并嗪基，嘧啶基或吡嗪基；n和m为1至4；R1代表氢；芳基；甲酰基；C1-6烷基羰基；C1-6烷氧羰基；可选择取代的C1-6烷基；C1-6烷氧基C1-6烷基羰基，其用作药物，用于制造用于治疗或预防HIV感染的药物的药物，其制备方法和包含它们的制药组合物。
• Pentaerythritol co-esters
  申请人：Mallinckrodt, Inc.

  公开号：US04734519A1

  公开（公告）日：1988-03-29

  Pentaerythritol co-esters derived from pentaerythritol, (3-alkyl-4-hydroxyphenyl)-alkanoic acids and alkylthioalkanoic acids or lower alkyl esters of such acids are useful as stabilizers of organic material normally susceptible to oxidative and/or thermal deterioration. The co-esters are advantageously prepared by transesterification of such esters with pentaerythritol. Preferred co-esters are (I) pentaerythritol tris[3-(3,5-di-tert-butyl-4-hydroxylphenyl)propionate]-mono[3-n-dodecylthi opropionate] and (II) pentaerythritol bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-bis[3-n-dodecylthiopr opionate]. The co-esters are especially useful in stabilizing applications for which physical mixtures of (i) (3-alkyl-4-hydroxyphenyl)alkanoic acid esters of polyols with (ii) polyalkanol esters of alkylthioalkanoic acids have heretofore been proposed.

  由五羟甲基四羧酸酯衍生的五羟甲基共酯，包括（3-烷基-4-羟基苯基）-脂肪酸和烷基硫脂肪酸或这些酸的低烷基酯，可用作有机材料的稳定剂，这些材料通常容易受到氧化和/或热降解的影响。这些共酯物是通过与五羟甲基四羧酸酯进行酯交换反应而得到的。首选的共酯物是（I）五羟甲基三[3-（3,5-二叔丁基-4-羟基苯基）丙酸酯]-单[3-正十二烷硫酸丙酸酯]和（II）五羟甲基双[3-（3,5-二叔丁基-4-羟基苯基）丙酸酯]-双[3-正十二烷硫酸丙酸酯]。这些共酯物在稳定应用中特别有用，先前已经提出了（i）聚醇的（3-烷基-4-羟基苯基）脂肪酸酯和（ii）烷基硫脂肪酸的聚烷基醇酯的物理混合物。
• Pentaerythritol co-esters containing sulfur in at least one of the acid
  申请人：Millinckrodt, Inc.

  公开号：US04772741A1

  公开（公告）日：1988-09-20

  Pentaerythritol co-esters derived from pentaerythritol, (3-alkyl-4-hydroxyphenyl)-alkanoic acids and alkylthioalkanoic acids or lower alkyl esters of such acids are useful as stabilizers of organic material normally susceptible to oxidative and/or thermal deterioration. The co-esters are advantageously prepared by transesterification of such esters with pentaerythritol. Preferred co-esters are (I) pentaerythritol tris[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-mono[3-n-dodecylthio propionate]and (II) pentaerythritol bis [3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-bis[3-n-dodecylthiopropi onate]. The co-esters are especially useful in stabilizing applications for which physical mixtures of (i) (3-alkyl-4-hydroxyphenyl)alkanoic acid esters of polyols with (ii) polyalkanol esters of alkylthioalkanoic acids have heretofore been proposed.

  由戊四醇，(3-烷基-4-羟基苯基)-脂肪酸和烷基硫醇脂肪酸或这些酸的较低烷基酯衍生的五羟甲基四元酯共酯是有用的有机材料稳定剂，通常易于氧化和/或热降解。这些共酯体优选通过戊四醇与这些酯的转酯化反应制备。优选的共酯体是(I)戊四醇三[3-(3,5-二叔丁基-4-羟基苯基)丙酸酯]-单[3-正十二烷硫酸酯]和(II)戊四醇双[3-(3,5-二叔丁基-4-羟基苯基)丙酸酯]-双[3-正十二烷硫酸酯]。这些共酯体在稳定物理混合物(i)(3-烷基-4-羟基苯基)酸酯聚醇与(ii)烷基硫酸酯的多羟基醇酯已经被提出的应用中特别有用。
• Pentaerythritol co-esters where up to 75 percent of the acid component
  申请人：Mallinckrodt, Inc.

  公开号：US04794138A1

  公开（公告）日：1988-12-27

  Pentaerythritol co-esters derived from pentaerythritol, (3-alkyl-4-hydroxyphenyl)-alkanoic acids and alkylthioalkanoic acids or lower alkyl esters of such acids are useful as stabilizers of organic material normally susceptible to oxidative and/or thermal deterioration. The co-esters are advantageously prepared by transesterification of such esters with pentaerythritol. Preferred co-esters are (I) pentaerythritol tris[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-mono[3-n-do-decylthi opropionate] and (II) pentaerythritol bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-bis[3-n-dodecylthiopr opionate]. The co-esters are especially useful in stabilizing applications for which physical mixtures of (i) (3-alkyl-4-hydroxyphenyl)alkanoic acid esters of polyols with (ii) polyalkanol esters of alkylthioalkanoic acids have heretofore been proposed.

  来自戊四醇，(3-烷基-4-羟基苯基)-脂肪酸和烷基硫代脂肪酸或这些酸的较低烷基酯衍生的戊四醇共酯体在有机材料通常易受氧化和/或热降解的稳定剂方面非常有用。这些共酯体是通过这些酯与戊四醇的酯交换反应优势制备的。首选的共酯体是(I)戊四醇三[3-(3,5-二-叔丁基-4-羟基苯基)丙酸酯]-单[3-正十二硫代丙酸酯]和(II)戊四醇双[3-(3,5-二-叔丁基-4-羟基苯基)丙酸酯]-双[3-正十二硫代丙酸酯]。这些共酯体在稳定应用中特别有用，之前已经提出将(i)(3-烷基-4-羟基苯基)脂肪酸酯与(ii)烷基硫代脂肪酸的多元醇酯的物理混合物用作稳定剂。
• Method of making mixed pentaerythritol esters having up to 75 percent
  申请人：Mallinckrodt, Inc.

  公开号：US04806675A1

  公开（公告）日：1989-02-21

  Pentaerythritol co-esters derived from pentaerythritol, (3-alkyl-4-hydroxyphenyl)-alkanoic acids and alkylthioalkanoic acids or lower alkyl esters of such acids are useful as stabilizers of organic material normally susceptible to oxidative and/or thermal deterioration. The co-esters are advantageously prepared by transesterification of such esters with pentaerythritol. Preferred co-esters are (I) pentaerythritol tris[3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-mono[3-n-dodecylthiopro pionate] and (II) pentaerythritol bis[-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]-bis[3-n-dodecylthiopro pionate]. The co-esters are especially useful in stabilizing applications for which physical mixtures of (i) (3-alkyl-4-hydroxyphenylalkanoic acid esters of polyols with (ii) polyalkanol esters of alkylthioalkanoic acids have heretofore been proposed.

  由Pentaerythritol、(3-烷基-4-羟基苯基)-脂肪酸和烷基硫代脂肪酸或这些酸的低级烷基酯制成的Pentaerythritol共酯是有用的有机材料稳定剂，通常容易受到氧化和/或热降解的影响。这些共酯通过与Pentaerythritol的酯交换反应优势地制备而成。首选的共酯是(I) Pentaerythritol三[3,5-二(叔丁基)-4-羟基苯基丙酸酯]-单[3-正十二烷硫代丙酸酯]和(II) Pentaerythritol双[-(3,5-二(叔丁基)-4-羟基苯基)丙酸酯]-双[3-正十二烷硫代丙酸酯]。这些共酯在稳定应用中特别有用，之前已经提出了(i)聚醇的(3-烷基-4-羟基苯基)脂肪酸酯与(ii)烷基硫代脂肪酸的聚烷醇酯的物理混合物。