(2S)-2-(3-(5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol | 1177419-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (2S)-2-(3-(5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol
• 英文别名: (2S)-2-(3-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol；(2S)-2-(3-{5-[(5S)-5-Methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl]-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol；(2S)-2-[3-[5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl]-5-(5-methylsulfonylpyrazin-2-yl)oxyphenoxy]propan-1-ol
• CAS: 1177419-61-2
• 化学式: C₂₂H₂₄N₄O₆S
• 分子量: 472.522
• InChiKey: KGVRRQUIOVPHPU-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 (2S)-2-(3-(5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol 以 水 、 丙酮 为溶剂， 以96.9%的产率得到(2S)-2-(3-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol monomethanesulfonate
  参考文献：
  名称：

  EP2703400

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazine 在 三溴化硼 、 水 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 以59%的产率得到(2S)-2-(3-(5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol
  参考文献：
  名称：

  NOVEL PHENYLPYRROLE DERIVATIVE

  摘要：

  公开号：

  EP2239253B1

文献信息

• Phenylpyrrole derivative
  申请人：Daiichi Sankyo Company, Limited

  公开号：US08017610B2

  公开（公告）日：2011-09-13

  The present invention relates to a compound or a pharmacologically acceptable salt thereof having superior glucokinase activating activity, and is a compound represented by general formula (I), or pharmacologically acceptable salt thereof: [wherein, A represents, for example, an oxygen atom or sulfur atom, R1 represents, for example, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 halogenated alkyl group, A and R1 together with the carbon atom bonded thereto form a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group α, R2 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group α or a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group α, R3 represents a hydroxy group or a C1-C6 alkoxy group, and Substituent Group α consists of, for example, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group substituted with 1 or 2 hydroxy group(s), a C1-C6 alkylsulfonyl group, and a group represented by the formula —V—NR5R6 (wherein, V represents a carbonyl group or a sulfonyl group, and R5 and R6 may be the same or different and respectively represent a hydrogen atom or a C1-C6 alkyl group, or R5 and R6 together with the nitrogen atom bonded thereto form a 4- to 6-membered saturated heterocycle that may be substituted with 1 or 2 group(s) independently selected from a C1-C6 alkyl group and a hydroxy group, and the 4- to 6-membered saturated heterocycle may further contain one oxygen atom or nitrogen atom)].

  本发明涉及一种具有优越的葡萄糖激酶激活活性的化合物或其药理学上可接受的盐，该化合物由通式（I）表示，或其药理学上可接受的盐：[其中，A代表例如氧原子或硫原子，R1代表例如C1-C6烷基、C1-C6烷氧基或C1-C6卤代烷基，A和R1与其结合的碳原子形成可能被1到3个独立选择的取代基α取代的杂环基，R2代表可能被1到5个独立选择的取代基α取代的苯基或可能被1到3个独立选择的取代基α取代的杂环基，R3代表羟基或C1-C6烷氧基，取代基α由例如卤素原子、C1-C6烷基、带有1或2个羟基的C1-C6烷基、C1-C6烷基磺酰基和由公式—V—NR5R6表示的基组成（其中，V代表羰基或磺酰基，R5和R6可能相同或不同，分别代表氢原子或C1-C6烷基，或者R5和R6与其结合的氮原子形成可能被1或2个独立选择的C1-C6烷基和羟基取代的4-6环饱和杂环，4-6环饱和杂环还可能含有一个氧原子或氮原子）。
• CRYSTALS OF PHENYLPYRROLE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：US20140121220A1

  公开（公告）日：2014-05-01

  Provided is a monomethanesulfonate of a phenylpyrrole derivative, having superior glucokinase activating activity and demonstrating remarkably improved solubility, hygroscopicity and stability as well as superior oral absorption, and crystals thereof. The present invention provides (2S)-2-(3-5-[(55)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol monomethanesulfonate having superior glucokinase activating activity, crystals thereof, a pharmaceutical containing the same, and a preventive and/or therapeutic agent for diabetes and the like.

  本发明提供了一种苯基吡咯衍生物的单甲磺酸盐，具有优异的葡萄糖激活酶活性，表现出明显改善的溶解度、吸湿性和稳定性以及优异的口服吸收性，以及其晶体。本发明提供了具有优异葡萄糖激活酶活性的(2S)-2-(3-5-[(55)-5-甲基-4,5-二氢-1,3-噁唑-2-基]-1H-吡咯-2-基}-5-[5-(甲磺酰基)吡嗪-2-基]氧基}苯氧基)丙醇单甲磺酸盐，其晶体，含有该化合物的制药组合物以及糖尿病等预防和/或治疗剂。
• PHENYL PYRROLE DERIVATIVE CRYSTAL
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2703400A1

  公开（公告）日：2014-03-05

  Provided is a monomethanesulfonate of a phenylpyrrole derivative, having superior glucokinase activating activity and demonstrating remarkably improved solubility, hygroscopicity and stability as well as superior oral absorption, and crystals thereof. The present invention provides (2S)-2-(3-5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-ol monomethanesulfonate having superior glucokinase activating activity, crystals thereof, a pharmaceutical containing the same, and a preventive and/or therapeutic agent for diabetes and the like.

  本发明提供了一种苯基吡咯衍生物的单甲磺酸盐及其晶体，该衍生物具有优异的葡萄糖激酶活化活性，并在溶解性、吸湿性和稳定性以及口服吸收方面有明显改善。本发明提供了具有优异葡萄糖激酶激活活性的 (2S)-2-(3-5-[(5S)-5-甲基-4,5-二氢-1,3-恶唑-2-基]-1H-吡咯-2-基}-5-[5-(甲磺酰基)吡嗪-2-基]氧基}苯氧基)丙-1-醇单甲磺酸酯、其晶体、含有相同成分的药物以及糖尿病的预防和/或治疗剂等。
• ORAL PREPARATION OF GLUCOKINASE ACTIVATOR AND PREPARATION METHOD THEREFOR
  申请人：Hua Medicine (Shanghai) Ltd.

  公开号：EP3556354A1

  公开（公告）日：2019-10-23

  The present invention relates to a solid dispersion and a preparation method therefor. The solid dispersion contains a glucokinase activator, an isotopic label thereof, or a medicinal salt thereof and a polymer support. The present invention further relates to a solid dispersion composition containing the solid dispersion and an excipient. The present invention also relates to an oral preparation of the glucokinase activator, containing the solid dispersion or the solid dispersion composition. The present invention also relates to a tablet and a capsule of the glucokinase activator and a preparation method therefor. In addition, the present invention also relates to uses of the solid dispersion, the solid dispersion composition and the oral preparations comprising the tablet and the capsule, which can be used for treating and/or preventing selected diseases or medical conditions and especially one or more diseases selected from type I diabetes mellitus, type II diabetes mellitus, impaired glucose tolerance, impaired fasting glucose and hyperglycemia.

  本发明涉及一种固体分散体及其制备方法。该固体分散体含有葡萄糖激酶激活剂、其同位素标记或其药用盐以及聚合物支持物。本发明还涉及一种含有该固体分散体和赋形剂的固体分散体组合物。本发明还涉及一种葡萄糖激酶激活剂口服制剂，其中含有固体分散体或固体分散体组合物。本发明还涉及葡萄糖激酶活化剂的片剂和胶囊及其制备方法。此外，本发明还涉及固体分散体、固体分散体组合物以及包含片剂和胶囊的口服制剂的用途，它们可用于治疗和/或预防选定的疾病或病症，尤其是一种或多种选自I型糖尿病、II型糖尿病、糖耐量受损、空腹血糖受损和高血糖症的疾病。
• US8017610B2
  申请人：——

  公开号：US8017610B2

  公开（公告）日：2011-09-13