(S)-4-[hydroxy[5-(imidazol-1-yl)-2-methylphenyl]methyl]-3,5-dimethylbenzoic acid | 122331-77-5

• 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: (S)-4-[hydroxy[5-(imidazol-1-yl)-2-methylphenyl]methyl]-3,5-dimethylbenzoic acid
• 英文别名: (S)-4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid；Benzoic acid, 4-((S)-hydroxy(5-(1H-imidazol-1-yl)-2-methylphenyl)methyl)-3,5-dimethyl-；4-[(S)-hydroxy-(5-imidazol-1-yl-2-methylphenyl)methyl]-3,5-dimethylbenzoic acid
• CAS: 122331-77-5
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: QSAHHFJAWATNBG-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl (S)-4-[5-(1-imidazolyl)-2-methyl-α-{(S)-2-(4-methylbenzenesulfonylamino)propionyloxy}benzyl]-3,5-dimethylbenzoate 以 N,N-二甲基甲酰胺 为溶剂， 以to give 10.5 g of (S)-4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, melting point 286-288° C. (decomposition), optical rotation [α]D21 -261.50 (c=1.0, dimethylformamide)的产率得到(S)-4-[hydroxy[5-(imidazol-1-yl)-2-methylphenyl]methyl]-3,5-dimethylbenzoic acid
  参考文献：
  名称：

  Process for producing optically active imidazole compounds,

  摘要：

  本发明提供了一种制备光学活性的4-[.alpha.-羟基-5-(1-咪唑基)-2-甲基苯基]-3,5-二甲基苯甲酸或其药学可接受的盐的方法，包括将式(I)的化合物进行光学分离，通过分数结晶得到其光学活性化合物，然后进行水解反应。根据这种方法，可以获得一种用于工业大规模生产4-[.alpha.-羟基-5-(1-咪唑基)-2-甲基苯基]-3,5-二甲基苯甲酸的光学活性化合物的分离方法，该化合物可用作血栓素合酶抑制剂和糖尿病并发症的预防和治疗剂。

  公开号：

  US06066739A1

文献信息

• Process for producing optically active imidazole compounds,
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US06066739A1

  公开（公告）日：2000-05-23

  The present invention provides a method for producing an optically active 4-[.alpha.-hydro-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid or a pharmaceutically acceptable salt thereof, which includes subjecting a compound of the formula (I) ##STR1## wherein each symbol in the formula is as defined in the specification, to optical resolution by fractional crystallization to give an optically active compound thereof and subjecting the compound to hydrolysis reaction. According to this method, a resolution method useful for industrial large-scale production of the optically active compound of 4-[.alpha.-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, which is useful as a thromboxane synthetase inhibitor and an agent for the prophylaxis and treatment of diabetic complications, can be obtained.

  本发明提供了一种生产光学活性4-[α-羟基-5-(1-咪唑基)-2-甲基苄基]-3,5-二甲基苯甲酸或其药用可接受盐的方法，包括将式(I)的化合物##STR1##其中方程式中的每个符号如规范中定义，通过分级结晶进行光学分辨，得到其光学活性化合物，并将该化合物进行水解反应。根据该方法，可以获得一种用于工业大规模生产4-[α-羟基-5-(1-咪唑基)-2-甲基苄基]-3,5-二甲基苯甲酸的光学活性化合物的分辨方法，该化合物可用作血栓素合酶抑制剂和糖尿病并发症的预防和治疗药物。
• METHOD OF ASYMMETRICALLY REDUCING 4- 5-(IMIDAZOL-1-YL)-2-MET HYLBENZOYL -3,5-DIMETHYL-BENZOIC ACID OR ESTER THEREOF
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1719764A1

  公开（公告）日：2006-11-08

  The invention relates to a method of producing an optically active 4-[hydroxy[5-(imidazol-1-yl)-2-methylphenyl]methyl]-3,5-dimethylbenzoic acid or an ester thereof, which includes reacting 4-[5-(imidazol-1-yl)-2-methylbenzoyl]-3,5-dimethylbenzoic acid or an ester thereof with a silane agent in the presence of a particular zinc compound and an optically active diamine compound.

  本发明涉及一种制备光学活性4-[羟基[5-(咪唑-1-基)-2-甲基苯基]甲基]-3,5-二甲基苯甲酸或其酯的方法，包括在特定的锌化合物和光学活性二胺化合物存在下，将4-[5-(咪唑-1-基)-2-甲基苯甲酰基]-3,5-二甲基苯甲酸或其酯与硅烷试剂反应。
• Method of asymmetrically reducing 4-[5-(imidazol-1-yl)-2-methylbenzoyl]-3,5- dimethylbenzoic acid or ester thereof
  申请人：Ushio Hiroyuki

  公开号：US20070161803A1

  公开（公告）日：2007-07-12

  The invention relates to a method of producing an optically active 4-[hydroxy[5-(imidazol-1-yl)-2-methylphenyl]methyl]-3,5-dimethylbenzoic acid or an ester thereof, which includes reacting 4-[5-(imidazol-1-yl)-2-methylbenzoyl]-3,5-dimethylbenzoic acid or an ester thereof with a silane agent in the presence of a particular zinc compound and an optically active diamine compound.

  本发明涉及一种制备光学活性4-[羟基[5-(咪唑-1-基)-2-甲基苯基]甲基]-3,5-二甲基苯甲酸或其酯的方法，包括在特定锌化合物和光学活性二胺化合物的存在下，将4-[5-(咪唑-1-基)-2-甲基苯甲酰基]-3,5-二甲基苯甲酸或其酯与硅烷试剂反应。
• PREVENTIVES/REMEDIES FOR COMPLICATIONS OF DIABETES
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0881218A1

  公开（公告）日：1998-12-02

  Preventives/remedies for complications of diabetes containing as the active ingredient 4-[α-hydroxy-2-methyl-5-(1-imidazolyl)benzyl]-3,5-dimethylbenzoic acid, optical isomers thereof or pharmaceutically acceptable salts thereof; and a method for preventing or treating complications of diabetes by administering the above compounds in an efficacious dose. These drugs are useful in the prevention and treatment of complications of diabetes such as diabetic neuropathy, nephropathy, ocular disorders and arterial sclerosis. Moreover, they can exhibit long lasting effects even in an extremely small dose, which makes it possible to take the drugs only once a day.

  预防/治疗糖尿病并发症的药物，其活性成分为 4-[α-羟基-2-甲基-5-(1-咪唑基)苄基]-3,5-二甲基苯甲酸、其光学异构体或其药学上可接受的盐；以及通过以有效剂量给药上述化合物来预防或治疗糖尿病并发症的方法。这些药物可用于预防和治疗糖尿病并发症，如糖尿病神经病变、肾病、眼部疾病和动脉硬化。此外，这些药物即使剂量极小，也能产生持久的疗效，因此每天只需服用一次即可。
• PROCESS FOR PRODUCING OPTICALLY ACTIVE IMIDAZOLE COMPOUNDS, INTERMEDIATES FOR SYNTHESIZING THE SAME, AND PROCESS FOR PRODUCING THE SAME
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0972768A1

  公开（公告）日：2000-01-19

  The present invention provides a method for producing an optically active 4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid or a pharmaceutically acceptable salt thereof, which includes subjecting a compound of the formula (I) wherein each symbol in the formula is as defined in the specification, to optical resolution by fractional crystallization to give an optically active compound thereof and subjecting the compound to hydrolysis reaction. According to this method, a resolution method useful for industrial large-scale production of the optically active compound of 4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, which is useful as a thromboxane synthetase inhibitor and an agent for the prophylaxis and treatment of diabetic complications, can be obtained.

  本发明提供了一种生产光学活性 4-[α-羟基-5-(1-咪唑基)-2-甲基苄基]-3,5-二甲基苯甲酸或其药学上可接受的盐的方法，该方法包括将式(I)化合物 其中式中各符号如说明书中所定义，通过分馏结晶进行光学解析，得到其光学活性化合物，并使该化合物进行水解反应。根据该方法，可以获得一种用于工业化大规模生产 4-[α-羟基-5-(1-咪唑基)-2-甲基苄基]-3,5-二甲基苯甲酸光学活性化合物的解析方法，该化合物可用作血栓素合成酶抑制剂和预防及治疗糖尿病并发症的药物。