methyl 6-[3-{(1S)-1-methyl-2-methoxy-ethoxy}-5-hydroxyphenylcarbonylamino]pyridine-3-carboxylate | 851885-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 6-[3-{(1S)-1-methyl-2-methoxy-ethoxy}-5-hydroxyphenylcarbonylamino]pyridine-3-carboxylate
• 英文别名: methyl 6-[3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]-benzoylamino]-3-pyridine carboxylate；methyl 6-{[(3-hydroxy-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}phenyl)carbonyl]amino}pyridine-3-carboxylate；methyl 6-[[3-hydroxy-5-[(2S)-1-methoxypropan-2-yl]oxybenzoyl]amino]pyridine-3-carboxylate
• CAS: 851885-39-7
• 化学式: C₁₈H₂₀N₂O₆
• 分子量: 360.367
• InChiKey: LOWSCKORGJWXKN-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 6-[3-{(1S)-1-methyl-2-methoxy-ethoxy}-5-hydroxyphenylcarbonylamino]pyridine-3-carboxylate 在 水 、 copper diacetate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 6-[3-{(1S)-1-methyl-2-methoxy-ethoxy}-5-{3-fluorophenoxy}phenylcarbonylamino]pyridine-3-carboxylic acid
  参考文献：
  名称：

  Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life

  摘要：

  The continued optimization of a series of glucokinase activators is described, including attempts to understand the interplay between molecular structure and the composite parameter of unbound clearance. These studies resulted in the discovery of a new scaffold for glucokinase activators and further exploration of this scaffold led to the identification of GKA60. GKA60 maintains an excellent balance of potency and physical properties whilst possessing a significantly different, but complimentary, preclinical pharmacokinetic profile compared with the previously disclosed compound GKA50. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.093
• 作为产物：
  描述：

  methyl 3-(benzyloxy)-5-[(1S)-2-methoxy-1-methylethoxy]benzoate 在 草酰氯 、 palladium on carbon 、 水 、 氢气 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 为溶剂， 生成 methyl 6-[3-{(1S)-1-methyl-2-methoxy-ethoxy}-5-hydroxyphenylcarbonylamino]pyridine-3-carboxylate
  参考文献：
  名称：

  Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life

  摘要：

  The continued optimization of a series of glucokinase activators is described, including attempts to understand the interplay between molecular structure and the composite parameter of unbound clearance. These studies resulted in the discovery of a new scaffold for glucokinase activators and further exploration of this scaffold led to the identification of GKA60. GKA60 maintains an excellent balance of potency and physical properties whilst possessing a significantly different, but complimentary, preclinical pharmacokinetic profile compared with the previously disclosed compound GKA50. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.093

文献信息

• [EN] BENZOYL AMINO PYRIDYL CARBOXYLIC ACID DERIVATIVES USEFUL AS GLUCOKINASE (GLK) ACTIVATORS<br/>[FR] DERIVES DE L'ACIDE BENZOYL-AMINO-PYRIDYL-CARBOXYLIQUE UTILES EN TANT QU'ACTIVATEURS DE LA GLUCOKINASE (GLK)
  申请人：ASTRAZENECA AB

  公开号：WO2005056530A1

  公开（公告）日：2005-06-23

  A compound of Formula (I): Formula (I) wherein: R1 is selected from hydrogen and C1-4alkyl; R2 is selected from: R4-C(R5aR5b)- , R4=C(R6)- and R7aC(R7b)=C(R6)-; R3 X- is selected from methyl, methoxymethyl and ; R4 is selected from (optionally substituted) C1-4alkyl, phenyl, C3-6cycloalkyl and heteroaryl; R5a and R5b are independently selected from hydrogen, fluoro and C1-4alkyl; R6 is selected from hydrogen and C1-4alkyl; R7a and R7b are optionally substituted C1-4alkyl; or a salt, pro-drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

  化合物的化学式（I）：化学式（I）其中：R1选择氢和C1-4烷基; R2选择自R4-C（R5aR5b）-，R4=C（R6）-和R7aC（R7b）=C（R6）-; R3X-选择甲基，甲氧甲基和; R4选择（可选取代）C1-4烷基，苯基，C3-6环烷基和杂环芳基; R5a和R5b独立选择氢，氟和C1-4烷基; R6选择氢和C1-4烷基; R7a和R7b是可选取代的C1-4烷基; 或其盐，前药或溶剂。描述了它们作为GLK激活剂的用途，包含它们的制药组合物以及它们的制备方法。
• [EN] BENZOYL AMINO PYRIDYL CARBOXYLIC ACID DERIVATIVES USEFUL AS GLUCOKINASE (GLK) ACTIVATORS<br/>[FR] DERIVES D'ACIDE BENZOYL-AMINO-PYRIDYL-CARBOXYLIQUE UTILISES EN TANT QU'ACTIVATEURS DE LA GLUCOKINASE (GLK)
  申请人：ASTRAZENECA AB

  公开号：WO2005054200A1

  公开（公告）日：2005-06-16

  Compounds of Formula: (I); wherein: R¹ is selected from: fluoro, chloro, C1-3alkyl and C1-3alkoxy; R²-X- is selected from: methyl, methoxymethyl and Formula: (X); n is 0,1 or 2; or a salt, pro-drug or solvate thereof are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

  式化合物：(I)；其中：R¹选择自：氟、氯、C1-3烷基和C1-3烷氧基；R²-X-选择自：甲基、甲氧甲基和式：(X)；n为0、1或2；或其盐、前药或溶剂化合物。描述了它们作为GLK激活剂的用途，含有它们的药物组合物，以及它们的制备方法。
• [EN] PYRIDINE CARBOXYLIC ACID DERIVATIVES AS GLUCOKINASE MODULATORS<br/>[FR] DERIVES D'ACIDES CARBOXYLIQUE DE PYRIDINE EN TANT QUE MODULATEURS DE LA GLUCOKINASE
  申请人：ASTRAZENECA AB

  公开号：WO2005044801A1

  公开（公告）日：2005-05-19

  A compound of Formula (I): wherein: A is phenyl or a 5- or 6-membered heteroaryl ring, optionally substituted; R1 and R2 are selected from hydrogen and methyl; with the proviso that at least one of R1 and R2 is methyl; or a salt, pro-drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

  式(I)的化合物：其中：A为苯基或5-或6-成员杂环芳基环，可选择地取代；R1和R2从氢和甲基中选取；条件是R1和R2中至少有一个为甲基；或其盐、前药或溶剂化合物。描述了它们作为GLK激活剂的用途，含有它们的药物组合物以及它们的制备方法。
• [EN] BENZOYL AMINO PYRIDIL CARBOXYLIC ACID DERIVATIVES AS GLUOKINASE ACTIVATORS<br/>[FR] DERIVES D'ACIDE CARBOXYLIQUE BENZOYL-AMINO-PYRIDILES UTILISES COMME ACTIVATEURS DE GLUCOKINASE
  申请人：ASTRAZENECA AB

  公开号：WO2005054233A1

  公开（公告）日：2005-06-16

  Compounds of Formula (I) wherein: R1-X- is selected from: methyl, methoxymethyl and Formula (X); R2 is selected from hydrogen, methyl, chloro and fluoro; n is 1 or 2; or a salt, pro-drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

  公式（I）中的化合物，其中：R1-X-选自：甲基，甲氧甲基和公式（X）；R2选自氢，甲基，氯和氟；n为1或2；或其盐，前药或溶剂化合物。描述了它们作为GLK激活剂的用途，含有它们的药物组合物，以及它们的制备方法。
• PYRIDINE CARBOXYLIC ACID DERIVATIVES AS GLUCOKINASE MODULATORS
  申请人：Caulkett William Rodney Peter

  公开号：US20070078168A1

  公开（公告）日：2007-04-05

  A compound of Formula (I): wherein: A is phenyl or a 5- or 6-membered heteroaryl ring, optionally substituted; R 1 and R 2 are selected from hydrogen and methyl; with the proviso that at least one of R 1 and R 2 is methyl; or a salt, pro-drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.

  公式（I）的化合物：其中：A为苯基或5或6成员的杂环芳基环，可选择取代；R1和R2为氢或甲基；但至少有一个R1和R2为甲基；或其盐、前药或溶剂化物。描述了它们作为GLK激活剂的用途，包含它们的制药组合物以及它们的制备方法。