6-[[((2S)-3-环戊基-1-氧代-2-[4-(三氟甲基)-1H-咪唑-1-基]丙基]氨基]-3-吡啶甲酸 | 1215197-37-7

• 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
• 中文名称: 6-[[((2S)-3-环戊基-1-氧代-2-[4-(三氟甲基)-1H-咪唑-1-基]丙基]氨基]-3-吡啶甲酸
• 英文名称: (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid
• 英文别名: PF-04991532；3-Pyridinecarboxylic acid, 6-(((2S)-3-cyclopentyl-1-oxo-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propyl)amino)-；6-[[(2S)-3-cyclopentyl-2-[4-(trifluoromethyl)imidazol-1-yl]propanoyl]amino]pyridine-3-carboxylic acid
• CAS: 1215197-37-7
• 化学式: C₁₈H₁₉F₃N₄O₃
• 分子量: 396.369
• InChiKey: GKMLFBRLRVQVJO-ZDUSSCGKSA-N

物化性质

• 沸点：
  646.5±55.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.1
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  6-[[((2S)-3-环戊基-1-氧代-2-[4-(三氟甲基)-1H-咪唑-1-基]丙基]氨基]-3-吡啶甲酸 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以100%的产率得到(S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinoyl chloride
  参考文献：
  名称：

  [EN] HETEROARYLS AMIDE DERIVATIVES AND THEIR USE AS GLUCOKINASE ACTIVATORS
  [FR] DÉRIVÉS D'AMIDES D'HÉTÉROARYLES ET LEUR UTILISATION COMME ACTIVATEURS DE LA GLUCOKINASE

  摘要：

  本发明提供了作为葡糖激酶激活剂的式(1A)化合物；其药物组合物；以及治疗由葡糖激酶介导的疾病、紊乱或状况的方法。其中，X、Y、Z、R1、R2、R3和R4如本文所述。

  公开号：

  WO2010029461A1
• 作为产物：
  描述：

  (R)-methyl 3-cyclopentyl-2-hydroxypropanoate 在 吡啶 、 2,6-二甲基吡啶 、 甲酸 、 palladium 10% on activated carbon 、 propylphosphonic anhydride 、 potassium carbonate 、 sodium hydroxide 作用下， 以 正己烷 、 水 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 36.83h， 生成 6-[[((2S)-3-环戊基-1-氧代-2-[4-(三氟甲基)-1H-咪唑-1-基]丙基]氨基]-3-吡啶甲酸
  参考文献：
  名称：

  Multikilogram Synthesis of a Hepatoselective Glucokinase Activator

  摘要：

  This work describes the process development and manufacture of early-stage clinical supplies of a hepatoselective glucokinase activator, a potential therapy for type 2 diabetes mellitus. Critical issues centered on challenges associated with the synthesis of intermediates and API bearing a particularly racemization-prone a-aryl carboxylate functionality. In particular, a T3P-mediated amidation process was optimized for the coupling of a racemization-prone acid substrate and a relatively non-nucleophilic amine. Furthermore, an unusually hydrolytically-labile amide in the API also complicated the synthesis and isolation of drug substance. The evolution of the process over multiple campaigns is presented, resulting in the preparation of over 110 kg of glucokinase activator.

  DOI：

  10.1021/op300194c

文献信息

• NOVEL PHENYLACETAMIDE COMPOUND AND PHARMACEUTICAL CONTAINING SAME
  申请人：KOWA COMPANY, LTD.

  公开号：US20150218151A1

  公开（公告）日：2015-08-06

  The present invention is to create a compound that selectively activates glucokinase in the liver, and in particular, to provide an agent for treating and preventing diabetes and impaired glucose tolerance, wherein the agent has a low hypoglycemia risk. A compound represented by the formula (1) as shown below, or a salt thereof, or a solvate of the compound or the salt: [wherein, in the following formula (1), ring A represents a thiazolyl group, a pyridyl group, a pyrazyl group, or a pyrazolyl group; L represents —(CO)—, —(CS)—, or —SO 2 —; and R 1 represents a C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a C 1-6 alkoxy group, an amino group, a C 1-6 alkylamino group, a hydroxyamino group, an N—C 1-6 alkylcarbamoyl group, or a group represented by the formula (2) as shown below, wherein R 3 represents a C 1-6 alkyl group; and R 2 represents a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, or a carboxyl group].

  本发明旨在创造一种在肝脏中选择性激活葡萄糖激酶的化合物，特别是提供一种治疗和预防糖尿病和糖耐量受损的药物，该药物具有低低血糖风险的药剂。化合物由以下式（1）表示，或其盐，或化合物或盐的溶剂合物：[式中，在以下式（1）中，环A表示噻唑基，吡啶基，吡唑基或吡唑基；L表示-（CO）-，-（CS）-或-SO2-；R1表示C1-6烷基，羟基C1-6烷基，C1-6烷氧基，氨基，C1-6烷基氨基，羟氨基，N-C1-6烷基氨基甲酰基或由以下式（2）表示的基团，其中R3表示C1-6烷基；R2表示氢原子，卤素原子，C1-6烷基，C1-6烷氧基或羧基。]
• Substituted imidazole propanamide glucokinase activators
  申请人：Pfizer Inc

  公开号：US07977367B2

  公开（公告）日：2011-07-12

  The present invention provides Formula (1A) compounds that act as glucokinase activators; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by glucokinase. X, Y, Z, R1, R2, R3, and R4 are as described herein.

  本发明提供了作为葡萄糖激酶激活剂的化合物公式（1A）；其制药组合物；以及通过葡萄糖激酶介导的疾病、障碍或病况的治疗方法。其中X、Y、Z、R1、R2、R3和R4如本文所述。
• Substituted Heteroaryls
  申请人：Benbow John William

  公开号：US20100063063A1

  公开（公告）日：2010-03-11

  The present invention provides Formula (1A) compounds that act as glucokinase activators; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by glucokinase. X, Y, Z, R 1 , R 2 , R 3 , and R 4 are as described herein.

  本发明提供了作为葡萄糖激酶激活剂的1A式化合物；其药物组合物；以及治疗由葡萄糖激酶介导的疾病，疾病或病状的方法。 X，Y，Z，R1，R2，R3和R4如本文所述。
• Multikilogram Synthesis of a Hepatoselective Glucokinase Activator
  作者：Joshua R. Dunetz、Martin A. Berliner、Yanqiao Xiang、Timothy L. Houck、Fabrice H. Salingue、Wang Chao、Chen Yuandong、Wang Shenghua、Yun Huang、Douglas Farrand、Steven J. Boucher、David B. Damon、Teresa W. Makowski、Mark T. Barrila、Raymond Chen、Isamir Martínez

  DOI：10.1021/op300194c

  日期：2012.10.19

  This work describes the process development and manufacture of early-stage clinical supplies of a hepatoselective glucokinase activator, a potential therapy for type 2 diabetes mellitus. Critical issues centered on challenges associated with the synthesis of intermediates and API bearing a particularly racemization-prone a-aryl carboxylate functionality. In particular, a T3P-mediated amidation process was optimized for the coupling of a racemization-prone acid substrate and a relatively non-nucleophilic amine. Furthermore, an unusually hydrolytically-labile amide in the API also complicated the synthesis and isolation of drug substance. The evolution of the process over multiple campaigns is presented, resulting in the preparation of over 110 kg of glucokinase activator.
• HETEROARYLS AMIDE DERIVATIVES AND THEIR USE AS GLUCOKINASE ACTIVATORS
  申请人：Pfizer Inc.

  公开号：EP2344458A1

  公开（公告）日：2011-07-20