3-(6-ethanesulfonyl-pyridin-3-yloxy)-5-((S)-2-hydroxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide | 752240-01-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(6-ethanesulfonyl-pyridin-3-yloxy)-5-((S)-2-hydroxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide
• 英文别名: 3-(6-ethanesulfonylpyridin-3-yloxy)-5-(2-hydroxy-1-methylethoxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide；3-(6-ethanesulfonylpyridin-3-yloxy)-5-((1S)-2-hydroxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide；MK-0941 free base；3-(6-ethylsulfonylpyridin-3-yl)oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)benzamide
• CAS: 752240-01-0
• 化学式: C₂₁H₂₄N₄O₆S
• 分子量: 460.511
• InChiKey: KJSGTWFWVTYPFZ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(6-ethanesulfonyl-pyridin-3-yloxy)-5-((S)-2-hydroxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide 、 甲烷磺酸 以 甲苯 、 乙腈 为溶剂， 反应 21.0h， 以22.9 kg的产率得到3-[[6-(乙基磺酰基)-3-吡啶基]氧基]-5-[(1S)-2-羟基-1-甲基乙氧基]-N-(1-甲基-1H-吡唑-3-基)苯甲酰胺甲烷磺酸盐
  参考文献：
  名称：

  A Large-Scale Synthesis of Potent Glucokinase Activator MK-0941 via Selective O-Arylation and O-Alkylation

  摘要：

  An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent S(N)2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.

  DOI：

  10.1021/op200068c
• 作为产物：
  描述：

  5-氯-2-(乙基磺酰基)吡啶 在 吡啶 、 盐酸 、 potassium tert-butylate 、 水 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 N,N-二甲基乙酰胺 、 水 、 甲苯 、 乙腈 为溶剂， 反应 3.5h， 生成 3-(6-ethanesulfonyl-pyridin-3-yloxy)-5-((S)-2-hydroxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide
  参考文献：
  名称：

  A Large-Scale Synthesis of Potent Glucokinase Activator MK-0941 via Selective O-Arylation and O-Alkylation

  摘要：

  An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent S(N)2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.

  DOI：

  10.1021/op200068c

文献信息

• METHOD FOR PRODUCING PYRAZOL-3-YL-BENZAMIDE DERIVATIVE
  申请人：Asakawa Kenichi

  公开号：US20100222394A1

  公开（公告）日：2010-09-02

  The present invention provides a more efficient industrial method for producing a pyrazol-3-yl-benzamide derivative expressed by a formula useful as medicine: wherein R 2 , R 3 and R 4 each independently represent a lower alkyl group.

  本发明提供了一种更有效的工业生产方法，用于生产一种表示为以下公式的作为药物有用的吡唑-3-基苯甲酰胺衍生物： 其中R2、R3和R4分别独立地表示较低的烷基基团。
• Heteroarylcarbamoylbenzene derivatives
  申请人：Iino Tomoharu

  公开号：US20090018056A1

  公开（公告）日：2009-01-15

  Compounds having glucokinase activating effects and being useful as treatments for diabetes, which are represented by the following formula (I): [wherein X 1 represents oxygen, etc., X 2 represents oxygen, etc., R 1 represents a group on Ring A such as alkylsulfonyl, etc., R 2 represents C3-7 cyclic alkyl optionally substituted with a halogen, etc., R 3 represents a substituent on Ring B such as lower alkyl, etc., formula (II): [Chemical Formula 1] represents 6- to 10-membered aryl, etc., and formula (III): [Formula 1] represents monocyclic or bicyclic heteroaryl optionally having on Ring B a substituent represented by R 3 above, wherein the carbon atom of Ring B which is bonded to the nitrogen atom of the amide group of formula (I) forms a C═N bond with the nitrogen atom of the ring], as well as their pharmaceutically acceptable salts.

  具有激活葡萄糖激酶效果且可用作糖尿病治疗的化合物，其化学式如下（I）：[其中X1代表氧等，X2代表氧等，R1代表环A上的基团，例如烷基磺酰等，R2代表C3-7环状烷基，可选择地被卤素等取代，R3代表环B上的取代基，例如低烷基等，化学式（II）：[化学式1]代表6到10成员芳基等，化学式（III）：[化学式1]代表单环或双环杂芳基，可选择地在环B上具有由上述R3代表的取代基，其中环B的碳原子与化学式（I）的酰胺基团的氮原子形成C═N键与环的氮原子结合]，以及其药学上可接受的盐。
• 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。
• HETEROARYLCARBAMOYLBENZENE DERIVATIVE
  申请人：MSD K.K.

  公开号：EP1600442B1

  公开（公告）日：2018-01-17
• AGENT
  申请人：Queen Mary University of London

  公开号：US20200268750A1

  公开（公告）日：2020-08-27

  The present invention relates to glycolysis-activating agents. The present invention also relates to the treatment or prevention of diseases or medical conditions, in particular immune-related diseases or medical conditions. In particular, the present invention also relates to agents for use in the treatment or prevention of a disease or medical condition, which treatment or prevention is mediated via the trafficking of endogenous regulatory T cells (Tregs).