4-t-Butyl-2-methylphenylacetonitrile | 205035-10-5

• 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-t-Butyl-2-methylphenylacetonitrile
• 英文别名: 2-(4-tert-butyl-2-methylphenyl)acetonitrile
• CAS: 205035-10-5
• 化学式: C₁₃H₁₇N
• 分子量: 187.285
• InChiKey: LPZSCLZQMVJBJH-UHFFFAOYSA-N

物化性质

• 沸点：
  287.1±9.0 °C(Predicted)
• 密度：
  0.943±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-t-Butyl-2-methylphenylacetonitrile 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 3.33h， 生成 2-[(4-t-butyl-2-methylphenyl)methyl]-4,5-dihydro-1H-imidazole
  参考文献：
  名称：

  Benzylimidazolines as h5-HT_1B/1D Serotonin Receptor Ligands: A Structure−Affinity Investigation

  摘要：

  Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1D alpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1D beta) receptor affinity by nearly 50-fold. The 2,6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding.With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.

  DOI：

  10.1021/jm970513p
• 作为产物：
  描述：

  4-叔丁基-2-甲基苯甲酸 在 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 四氢呋喃 、 乙醇 、 水 、 苯 为溶剂， 反应 4.5h， 生成 4-t-Butyl-2-methylphenylacetonitrile
  参考文献：
  名称：

  Benzylimidazolines as h5-HT_1B/1D Serotonin Receptor Ligands: A Structure−Affinity Investigation

  摘要：

  Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1D alpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1D beta) receptor affinity by nearly 50-fold. The 2,6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding.With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.

  DOI：

  10.1021/jm970513p

文献信息

• [EN] IMIDAZOLES WITH SEROTONIN RECEPTOR BINDING ACTIVITY<br/>[FR] IMIDAZOLES A ACTIVITE DE FIXATION DU RECEPTEUR DE LA SEROTONINE
  申请人：ALLELIX BIOPHARMACEUTICALS INC.

  公开号：WO1998012183A1

  公开（公告）日：1998-03-26

  (EN) This invention relates to compounds having serotonin receptor binding activity, to pharmaceutical compositions containing them and to their medical use, particularly in the treatment of CNS conditions. Described herein are compounds which have general formula (I), wherein R1 is selected from H, C1-6alkyl and benzyl; R2 is selected from H and C1-6alkyl; R3 is selected from H and C1-6alkyl; R4 is selected from C1-6alkyl and halo; R5 is selected from H and OH; and salts, hydrates and solvates thereof. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of subtypes of the serotonin receptor is implicated, such as migraine.(FR) L'invention porte sur des composés présentant une activité de fixation du récepteur de la sérotonine, sur des préparations pharmaceutiques les contenant et sur leurs utilisations médicales notamment pour le traitement des troubles du SNC, ainsi que sur leurs sels, hydrates et solvates. Lesdits composés répondent à la formule générale (I) dans laquelle: R1 est sélectionné parmi H, C1-6 alkyle et benzyle; R2 est sélectionné parmi H et C1-6 alkyle; R3 est sélectionné parmi H et C1-6 alkyle; R4 est sélectionné parmi C1-6 alkyle et halo; R5 est sélectionné parmi H et OH. L'invention porte également sur l'utilisation de ces composés comme produits pharmaceutiques pour traiter les cas où la stimulation des sous-types du récepteur de la sérotonine est en cause, tels que la migraine.

  本发明涉及具有5-羟色胺受体结合活性的化合物，包含它们的药物组成物以及它们在治疗中枢神经系统疾病方面的医学用途。本文描述了通式（I）的化合物，其中R1选自H、C1-6烷基和苄基；R2选自H和C1-6烷基；R3选自H和C1-6烷基；R4选自C1-6烷基和卤素；R5选自H和OH；以及它们的盐、水合物和溶剂化物。还描述了将这些化合物用作药物，以治疗与5-羟色胺受体亚型刺激有关的症状，例如偏头痛。
• Imidazoles with serotonin receptor binding activity
  申请人：Virginia Commonwealth University

  公开号：US06288101B1

  公开（公告）日：2001-09-11

  This invention relates compounds having serotonin receptor binding activity, to pharmaceutical compositions containing them and to their medical use, particularly in the treatment of CNS conditions. Described herein are compounds which have the general formula: wherein R1 is selected from H, C1-6alkyl and benzyl; R2 is selected from H and C1-6alkyl; R3 is selected from H and C1-6alkyl; R4 is selected from C1-6alkyl and halo; R5 is selected from H and OH; and salts, hydrates and solvates thereof. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of subtypes of the serotonin receptor is implicated, such as migraine.

  本发明涉及具有血清素受体结合活性的化合物，包含它们的制药组合物以及它们在医学上的应用，特别是在中枢神经系统疾病的治疗中。在此描述的化合物具有以下一般式： 其中，R1选自H，C1-6烷基和苄基；R2选自H和C1-6烷基；R3选自H和C1-6烷基；R4选自C1-6烷基和卤素；R5选自H和OH；以及其盐、水合物和溶剂化物。此外，还描述了这些化合物作为药物治疗刺激血清素受体亚型引起的适应症，例如偏头痛。
• Benzylamidine derivatives with serotonin receptor binding activity
  申请人：Virginia Commonwealth University

  公开号：US05969137A1

  公开（公告）日：1999-10-19

  This invention relates to compounds having serotonin receptor binding activity, to pharmaceutical compositions containing them and to their medical use, particularly in the treatment of CNS conditions. Described herein are compounds which have the general formula: ##STR1## wherein R.sup.1 is selected from a group of Formula i and ii: ##STR2## n is 1-3; R.sup.2 is selected from H and C.sub.1-6 alkyl; R.sup.3 is selected from H and C.sub.1-6 alkyl; R.sup.4 is selected from C.sub.1-6 alkyl, halo, phenyl, amino and nitro; R.sup.5 is selected from H, C.sub.1-6 alkyl and arylalkyl; R.sup.6 is selected from H or a alkylene group which is bonded to R.sup.4 to form the naphthalene ring skeleton; and salts, hydrates and solvates thereof. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of subtypes of the serotonin receptor is implicated, such as migraine.

  本发明涉及具有血清素受体结合活性的化合物，含有它们的制药组合物及其医疗用途，特别是在中枢神经系统疾病的治疗方面。本文描述的是具有一般式的化合物：##STR1## 其中R.sup.1选自公式i和ii的一组：##STR2## n为1-3；R.sup.2选自H和C.sub.1-6烷基；R.sup.3选自H和C.sub.1-6烷基；R.sup.4选自C.sub.1-6烷基，卤素，苯基，氨基和硝基；R.sup.5选自H，C.sub.1-6烷基和芳基烷基；R.sup.6选自H或与R.sup.4连接形成萘环骨架的烷基链；以及其盐，水合物和溶剂化合物。还描述了将这些化合物用作药物，以治疗刺激血清素受体亚型的适应症，如偏头痛。
• US06048862
  申请人：——

  公开号：——

  公开（公告）日：——
• US5969137A
  申请人：——

  公开号：US5969137A

  公开（公告）日：1999-10-19