2-Methylphenyl-(3-methyl-thien-2-yl)methanol | 112064-24-1

• 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: 2-Methylphenyl-(3-methyl-thien-2-yl)methanol
• 英文别名: 2-Methylphenyl-(3-methyl-2-thienyl)methanol；(2-methylphenyl)-(3-methylthiophen-2-yl)methanol
• CAS: 112064-24-1
• 化学式: C₁₃H₁₄OS
• 分子量: 218.32
• InChiKey: DRTQKVNJIVIKMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-Methylphenyl-(3-methyl-thien-2-yl)methanol 在 重铬酸吡啶 作用下， 生成 2-methylphenyl(3-methyl-2-thienyl)methanone
  参考文献：
  名称：

  Synthesis of Novel GABA Uptake Inhibitors. 3. Diaryloxime and Diarylvinyl Ether Derivatives of Nipecotic Acid and Guvacine as Anticonvulsant Agents

  摘要：

  (3R)-1-[4,4-双(3-甲基-2-噻吩基)-3-丁炔基]乙酸（丙戊酸钠，商品名：Gabitril）是一种强效且选择性的γ-氨基丁酸（GABA）摄取抑制剂，在人类中已被证实具有抗惊厥效果。这种药物在已上市的抗惊厥药物中具有独特的作用机制，目前已被批准用于12岁以上患者的部分性癫痫发作的辅助治疗，无论是否伴有继发性全面性发作。 以此新型药物作为参考，我们设计了两个系列的新型GABA摄取抑制剂，这些抑制剂展现出显著的 potency。我们采用了GABA转运蛋白类型1（GAT-1）摄取位点上的一种新型配体相互作用模型。该模型假设GABA摄取抑制剂中的一个带负电的区域与GAT-1位点蛋白质结构中的一个带正电的区域发生相互作用。 这两个系列的新型抗癫痫药物包含 diaryloxime 或 diarylvinyl醚功能基团，并与环状氨基酸部分相连。它们是从已知的4,4-二芳基-1-丁烯基GABA摄取抑制剂出发，利用新模型并通过一系列设计步骤衍生而来的。 实验表明，这些新化合物在体外对大鼠脑突触体中的[H-3]-GABA摄取表现出强效抑制作用，且在体内通过保护小鼠免受苯二氮卓受体反向激动剂——甲基4-乙基-6,7-二甲氧基-β-咔啉-3-羧酸酯（DMCM）引起的癫痫发作，进一步证明了它们的抗癫痫潜力。 通过这些新型GABA摄取抑制剂的构效关系研究，我们发现：在丙戊酸钠的骨架中引入与双键共轭的醚氧键（Ki = 67 nM）可使体外活性提高5倍，达到14 nM的效力。

  DOI：

  10.1021/jm981027k
• 作为产物：
  描述：

  3-甲基噻吩醛 、 2-溴甲苯 在 magnesium 作用下， 以 乙醚 为溶剂， 生成 2-Methylphenyl-(3-methyl-thien-2-yl)methanol
  参考文献：
  名称：

  Amino acid derivatives

  摘要：

  式I的化合物 其中，R1代表苯基或苯基取代物，所述苯基取代物由卤素、C1-7烷基和C1-7烷氧基中的一种或多种取代基所选，R2代表呋喃基、噻吩基、吡啶基或吡咯基，其邻位取代C1-7烷基或卤素，R3代表3-羧基哌啶-1-基、3-羧基-1,2,5,6-四氢吡啶-1-基或3-羧甲基吡咯烷-1-基。本发明还涉及含有式I化合物有效量的制药组合物以及通过给予式I化合物治疗中枢神经系统疾病的方法。

  公开号：

  US04931450A1

文献信息

• Design, synthesis, and structure–activity relationships of pyrazolo[3,4-d]pyrimidines: a novel class of potent enterovirus inhibitors
  作者：Jyh-Haur Chern、Kak-Shan Shia、Tsu-An Hsu、Chia-Liang Tai、Chung-Chi Lee、Yen-Chun Lee、Chih-Shiang Chang、Sung-Nien Tseng、Shin-Ru Shih

  DOI：10.1016/j.bmcl.2004.02.092

  日期：2004.5

  A series of pyrazolo[3,4-d]pyrimidines were synthesized. and their antiviral activity was evaluated in a plaque reduction assay. It is very interesting that this class of compounds provide remarkable evidence that they are very specific for human enteroviruses, in particular, coxsackieviruses. Some derivatives proved to be highly effective in inhibiting enterovirus replication at nanomolar concentrations. SAR studies revealed that the phenyl group at the N-I position and the hydrophobic diarylmethyl group at the piperazine largely influenced the in vitro antienteroviral activity of this new class of potent antiviral agents. It was found that the pyrazolo[3,4-d]pyrimidines with a thiophene substituent, such as compounds 20 24, in general exhibited high activity against coxsackievirus B3 (IC50 = 0.063-0.089 muM) and moderate activity against enterovirus 71 (IC50 = 0.32-0.65 muM) with no apparent cytotoxic effect toward RD (rhabdomyosarcoma) cell lines (CC50>25 muM). (C) 2004 Elsevier Ltd. All rights reserved.
• Novel amino acid derivatives
  申请人：NOVO NORDISK A/S

  公开号：EP0231996B1

  公开（公告）日：1993-10-06
• US4931450A
  申请人：——

  公开号：US4931450A

  公开（公告）日：1990-06-05
• Synthesis of Novel GABA Uptake Inhibitors. 3. Diaryloxime and Diarylvinyl Ether Derivatives of Nipecotic Acid and Guvacine as Anticonvulsant Agents
  作者：Lars J. S. Knutsen、Knud Erik Andersen、Jesper Lau、Behrend F. Lundt、Rodger F. Henry、Howard E. Morton、Lars Nærum、Hans Petersen、Henrik Stephensen、Peter D. Suzdak、Michael D. B. Swedberg、Christian Thomsen、Per O. Sørensen

  DOI：10.1021/jm981027k

  日期：1999.9.1

  (3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-buteny] acid 1(tiagabine, Gabitril) is a potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. This drug, which has a unique mechanism of action among marketed anticonvulsant agents, has been launched for add-on treatment of partial seizures with or without secondary generalization in patients > 12 years of age. Using this new agent as a benchmark, we have designed two series of novel GABA uptake inhibitors of remarkable potency, using a putative new model of ligand interaction at the GABA transporter type 1 (GAT-1) uptake site. This model involves the postulated interaction of an electronegative region in the CABA uptake inhibitor with a positively charged domain in the protein structure of the GAT-1 site. These two novel series of anticonvulsant agents contain diaryloxime or diarylvinyl ether functionalities linked to cyclic amino acid moieties and were derived utilizing the new model, via a series of design steps from the known 4,4-diarylbutenyl GABA uptake inhibitors. The new compounds are potent inhibitors of [H-3]-GABA uptake in rat brain synaptosomes in vitro, and their antiepileptic potential was demonstrated in vivo by their ability to protect against seizures induced by the benzodiazepine receptor inverse agonist methyl 4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate (DMCM) in mice. From structure-activity studies of these new GABA uptake inhibitors, we have shown that insertion of an ether oxygen in conjugation with the double bond in tiagabine (K-i = 67 nM) improves in vitro potency by 5-fold to 14 nM.

  (3R)-1-[4,4-双(3-甲基-2-噻吩基)-3-丁炔基]乙酸（丙戊酸钠，商品名：Gabitril）是一种强效且选择性的γ-氨基丁酸（GABA）摄取抑制剂，在人类中已被证实具有抗惊厥效果。这种药物在已上市的抗惊厥药物中具有独特的作用机制，目前已被批准用于12岁以上患者的部分性癫痫发作的辅助治疗，无论是否伴有继发性全面性发作。 以此新型药物作为参考，我们设计了两个系列的新型GABA摄取抑制剂，这些抑制剂展现出显著的 potency。我们采用了GABA转运蛋白类型1（GAT-1）摄取位点上的一种新型配体相互作用模型。该模型假设GABA摄取抑制剂中的一个带负电的区域与GAT-1位点蛋白质结构中的一个带正电的区域发生相互作用。 这两个系列的新型抗癫痫药物包含 diaryloxime 或 diarylvinyl醚功能基团，并与环状氨基酸部分相连。它们是从已知的4,4-二芳基-1-丁烯基GABA摄取抑制剂出发，利用新模型并通过一系列设计步骤衍生而来的。 实验表明，这些新化合物在体外对大鼠脑突触体中的[H-3]-GABA摄取表现出强效抑制作用，且在体内通过保护小鼠免受苯二氮卓受体反向激动剂——甲基4-乙基-6,7-二甲氧基-β-咔啉-3-羧酸酯（DMCM）引起的癫痫发作，进一步证明了它们的抗癫痫潜力。 通过这些新型GABA摄取抑制剂的构效关系研究，我们发现：在丙戊酸钠的骨架中引入与双键共轭的醚氧键（Ki = 67 nM）可使体外活性提高5倍，达到14 nM的效力。
• Amino acid derivatives
  申请人：Novo Industri A/S

  公开号：US04931450A1

  公开（公告）日：1990-06-05

  Compounds of the Formula I ##STR1## wherein R.sup.1 represents phenyl, or phenyl substituted by one, or more substituents selected from the group consisting of halogen, C.sub.1-7 -alkyl, and C.sub.1-7 -alkoxy, R.sup.2 represents furanyl, thienyl, pyridyl or pyrrolyl ortho substituted with C.sub.1-7 -alkyl or halogen and wherein R.sup.3 represents 3-carboxypiperidin-1-yl, 3-carboxy-1,2,5,6-tetrahydropyridin-1-yl or 3-carboxymethyl-pyrrolidin-1-yl, pharmaceutical compositions containing effective amounts of a compound of formula I and treatment of central nervous system ailments by administering a compound of formula I.

  式I的化合物 其中，R1代表苯基或苯基取代物，所述苯基取代物由卤素、C1-7烷基和C1-7烷氧基中的一种或多种取代基所选，R2代表呋喃基、噻吩基、吡啶基或吡咯基，其邻位取代C1-7烷基或卤素，R3代表3-羧基哌啶-1-基、3-羧基-1,2,5,6-四氢吡啶-1-基或3-羧甲基吡咯烷-1-基。本发明还涉及含有式I化合物有效量的制药组合物以及通过给予式I化合物治疗中枢神经系统疾病的方法。