4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxy phenyl]thio]butanoic acid | 105077-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxy phenyl]thio]butanoic acid
• 英文别名: 4-(3,5-di-t-butyl-4-hydroxyphenylthio)butyric acid；Butanoic acid, 4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-；4-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylbutanoic acid
• CAS: 105077-31-4
• 化学式: C₁₈H₂₈O₃S
• 分子量: 324.485
• InChiKey: JSGBATMAAQLVPD-UHFFFAOYSA-N

物化性质

• 沸点：
  435.3±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxy phenyl]thio]butanoic acid 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 4-({[(4-chlorophenyl)sulfonyl]amino}carbonyl)benzoyl-N-ε-{[(4-hydroxy-3,5-di-tert-butylphenyl)thio]butyroyl}-Lys-(2S,3aS,7aS)-Phi-(R,S)-Val-CF3
  参考文献：
  名称：

  Dual Inhibition of Human Leukocyte Elastase and Lipid Peroxidation:  In Vitro and in Vivo Activities of Azabicyclo[2.2.2]octane and Perhydroindole Derivatives

  摘要：

  A series of potent and selective human leukocyte elastase (HLE) inhibitors of the Val-Pro-Val type has been developed. Initially, the central proline residue was replaced by nonnatural amino acids Phi ((2S,3aS,7aS)-perhydroindole-2-carboxy acid) and Abo ((3S)-2-azabicyclo[2.2.2]octane-3-carboxylic acid), and secondly several groups able to confer antioxidant properties to the molecule were introduced at the lipophilic N-terminal side chain. When compared to reference inhibitors, in vitro HLE inhibitory potency was maintained (10-100 nM) both with compounds containing the antioxidant moiety at the end of the N-terminal side chain and with compounds in which the N-terminal valine of the tripeptidic sequence had been replaced by a epsilon-substituted lysine. The lipidic peroxidation inhibitory potency of this series of inhibitors was found to be similar to that of the reference antioxidant compounds (around 1 mu M). Moreover, HLE-induced hemorrhage in the hamster lung was effectively prevented (40-60% at 15 mu g/ kg) by most of the inhibitors tested when administered intratracheally 3 h before instillation of elastase. Among the most active analogs, compounds 11a,c,g were still active when administered 18 h before elastase. Interestingly, compound 14a was able to prevent HLE-mediated lung damage when administered 72 h prior to enzymatic challenge, indicating exceptional stability and retention in the lung. Finally, in a 14-day chronic model of emphysema in the hamster, 14a significantly conserved alveolar spaces, a marker of lung tissue destruction, send was more potent; than reference inhibitor ICI 200 880. This indicates that addition of peroxidation inhibitory properties to an HLE inhibitor can provide a powerful in vivo inhibitor of pulmonary tissue destruction.

  DOI：

  10.1021/jm960772z
• 作为产物：
  描述：

  2,6-二叔丁基-4-巯基苯酚 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxy phenyl]thio]butanoic acid
  参考文献：
  名称：

  Dual Inhibition of Human Leukocyte Elastase and Lipid Peroxidation:  In Vitro and in Vivo Activities of Azabicyclo[2.2.2]octane and Perhydroindole Derivatives

  摘要：

  A series of potent and selective human leukocyte elastase (HLE) inhibitors of the Val-Pro-Val type has been developed. Initially, the central proline residue was replaced by nonnatural amino acids Phi ((2S,3aS,7aS)-perhydroindole-2-carboxy acid) and Abo ((3S)-2-azabicyclo[2.2.2]octane-3-carboxylic acid), and secondly several groups able to confer antioxidant properties to the molecule were introduced at the lipophilic N-terminal side chain. When compared to reference inhibitors, in vitro HLE inhibitory potency was maintained (10-100 nM) both with compounds containing the antioxidant moiety at the end of the N-terminal side chain and with compounds in which the N-terminal valine of the tripeptidic sequence had been replaced by a epsilon-substituted lysine. The lipidic peroxidation inhibitory potency of this series of inhibitors was found to be similar to that of the reference antioxidant compounds (around 1 mu M). Moreover, HLE-induced hemorrhage in the hamster lung was effectively prevented (40-60% at 15 mu g/ kg) by most of the inhibitors tested when administered intratracheally 3 h before instillation of elastase. Among the most active analogs, compounds 11a,c,g were still active when administered 18 h before elastase. Interestingly, compound 14a was able to prevent HLE-mediated lung damage when administered 72 h prior to enzymatic challenge, indicating exceptional stability and retention in the lung. Finally, in a 14-day chronic model of emphysema in the hamster, 14a significantly conserved alveolar spaces, a marker of lung tissue destruction, send was more potent; than reference inhibitor ICI 200 880. This indicates that addition of peroxidation inhibitory properties to an HLE inhibitor can provide a powerful in vivo inhibitor of pulmonary tissue destruction.

  DOI：

  10.1021/jm960772z

文献信息

• Phenolic thioethers, sulfoxides, and disulfides as inhibitors of
  申请人：G. D. Searle & Co.

  公开号：US05002967A1

  公开（公告）日：1991-03-26

  The compounds of the present invention comprise substituted phenolic thioethers, sulfoxides, and disulfides that are specific inhibitors of 5-lipoxygenase and which, therefore, are useful in the treatment of local and systemic inflammation, allergy and hypersensitivity reactions and other disorders in which agents formed in the 5-lipoxygenase metablic pathway are involved.

  本发明的化合物包括取代酚硫醚、亚砜和二硫化物，它们是5-脂氧合酶的特异性抑制剂，因此在治疗局部和全身炎症、过敏和过敏反应以及其他涉及5-脂氧合酶代谢途径中形成的药物的紊乱方面具有用处。
• Novel disubstituted 4-hydroxyphenylthio anilides
  申请人：G. D. Searle & Co.

  公开号：US05071876A1

  公开（公告）日：1991-12-10

  The compounds of this invention are anilides represented by the formula: ##STR1## wherein: R.sub.1 and R.sub.2 are the same or different members of the group consisting of halo, phenyl, substituted phenyl and a ##STR2## group wherein n, m and p are independently an integer of from 1 to 8 provided that n+m+p is equal to or less than 10; X is thio, sulfinyl or sulfonyl; Alk is straight or branched chain lower alkylene; R.sub.3 is hydrogen or lower alkyl; and R.sub.4 is phenyl or substituted phenyl. The compounds of the present invention are useful in the treatment of inflammation, allergy and hypersensitivity reactions and other disorders of the immune system.

  本发明的化合物是酰替苯胺，其由下式表示：##STR1## 其中：R.sub.1和R.sub.2是相同或不同的卤素、苯基、取代苯基以及一个##STR2##基团，其中n、m和p是独立地从1到8的整数，只要n+m+p等于或小于10；X是硫代、亚磺酰基或磺酰基；Alk是直链或支链的低级烷基；R.sub.3是氢或低级烷基；R.sub.4是苯基或取代苯基。本发明的化合物可用于治疗炎症、过敏和超敏反应以及免疫系统等其他疾病。
• Method of treating inflammation, allergy, asthma and proliferative skin
  申请人：G. D. Searle & Co.

  公开号：US04959364A1

  公开（公告）日：1990-09-25

  The compounds of this invention are heterocyclic amides represented by the formula: ##STR1## wherein: R.sub.1 R.sub.2 are the same or different members of the group consisting of halo, phenyl, substituted phenyl and a ##STR2## group wherein q, r and t are independently an integer of from 1 to 8 provided that q+r+t is equal to or less than 10; y is thio, sulfinyl or sulfonyl; Alk is straight or branched chain lower alkylene, and R.sub.3 is a heterocyclic amine represented by the formula: ##STR3## wherein R.sub.4 is selected from the group consisting of hydrogen, lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, carboxyl or carboxyloweralkyl; X is selected from the group consisting of N--R.sub.4, O and CH.sub.2 ; m is 2 or 3; n is 2 or 3 when X is O or N--R.sup.4, and n is 1 to 3 when x is CH.sub.2 ; p is 0 to 2; and the pharmaceutically acceptable salts thereof. The compounds are anti-inflammatory and anti-allergy agents.

  本发明的化合物是由以下式表示的杂环酰胺：##STR1##其中：R.sub.1 R.sub.2 是由卤素、苯基、取代苯基和一个##STR2##基团中的相同或不同成员，其中q、r和t独立地是1到8的整数，前提是q+r+t等于或小于10；y是硫、亚硫酰基或磺酰基；Alk是直链或支链较低的烷基，R.sub.3 是由以下式表示的杂环胺：##STR3##其中R.sub.4 选自氢、较低烷基、苯基、取代苯基、苄基、取代苄基、羧基或羧基较低烷基的群；X选自N--R.sub.4、O和CH.sub.2；m是2或3；当X为O或N--R.sup.4时，n是2或3，当x为CH.sub.2时，n是1到3；p为0到2；以及其药用盐。这些化合物是抗炎和抗过敏剂。
• Acylaminoalkylpyridineamides as inhibitors of metastasis
  申请人：G. D. Searle & Co.

  公开号：US05030642A1

  公开（公告）日：1991-07-09

  The present invention relates to a method of inhibiting tumor metastasis in an aminal by administering to an animal in need of such treatment an acrylaminoalkylpryridineamides represented by the formula ##STR1## wherein: R.sub.1 and R.sub.2 are the same or different members of the group consisting of halo, phenyl, substituted phenyl and a ##STR2## group wherein n, m and p are independently an integer of from 1 to 8 provided n+m+p is equal to or less than 10; x is thio or sulfinyl; Alk.sub.1 is straight or branched chain lower alkylene of 1 to 6 carbon atoms, R.sub.3 is hydrogen or lower alkyl, Alk.sub.2 is straight or branched chain alkylene of 1 to 4 carbon atoms; R.sub.4 is selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl and lower alkoxy; or a pharmaceutically acceptable salt thereof, in an amount effective to inhibit tumor metastasis.

  本发明涉及一种通过向需要此类治疗的动物投与下列式所代表的丙烯基吡啶酰胺类物质来抑制动物体内肿瘤转移的方法： 其中：R.sub.1和R.sub.2是卤素、苯基、取代苯基和一个##STR2##基团中相同或不同的成员，其中n、m和p分别是1到8的整数，但要求n+m+p小于等于10；x为硫代基或亚硫代基；Alk.sub.1为1到6个碳原子的直链或支链较低烷基，R.sub.3为氢或较低烷基，Alk.sub.2为1到4个碳原子的直链或支链烷基；R.sub.4选自氢、卤素、羟基、较低烷基和较低烷氧基的群；或其药学上可接受的盐，在有效量下，用于抑制肿瘤转移。
• Acylaminoalkylpyridines ad use in treatment of inflammation and allergy
  申请人：G. D. Searle & Co.

  公开号：US04663333A1

  公开（公告）日：1987-05-05

  The compounds of this invention are acylaminoalkylpyridines representd by the formula ##STR1## wherein: R.sub.1 and R.sub.2 are the same or different members of the group consisting of halo, phenyl, substituted phenyl and a ##STR2## group wherein n, m and p are independently an integer of from 1 to 8 provided n+m+p is equal to or less than 10; X is thio, sulfinyl or sulfonyl; Alk.sub.1 is straight or branched chain lower alkylene of 1 to 6 carbon atoms, R.sub.3 is lower alkyl, Alk.sub.2 is straight or branched chain alkylene of 1 to 4 carbon atoms; R.sub.4 is selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl and lower alkoxy; and the pharmaceutically acceptable salts thereof. The compounds of the present invention are useful in the treatment of inflammation, allergy and hypersensitivity reactions and other disorders of the immune system.

  本发明的化合物是由以下式表示的酰胺基烷基吡啶：其中：R.sub.1和R.sub.2是卤素、苯基、取代苯基和##STR2##基的相同或不同成员，其中n、m和p分别是1到8的整数，且n+m+p等于或小于10；X是硫、亚砜基或砜基；Alk.sub.1是1到6个碳原子的直链或支链低碳烷基，R.sub.3是低碳基，Alk.sub.2是1到4个碳原子的直链或支链烷基；R.sub.4选自氢、卤素、羟基、低烷基和低烷氧基的组成成员；以及其药用盐。本发明的化合物在治疗炎症、过敏和过敏反应以及其他免疫系统疾病方面具有用途。