2-甲基-2-丙基5-氨基-2-吡嗪羧酸酯 | 710322-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-甲基-2-丙基5-氨基-2-吡嗪羧酸酯
• 英文名称: tert-butyl 5-aminopyrazine-2-carboxylate
• 英文别名: 5-amino-pyrazine-2-carboxylic acid tert-butyl ester
• CAS: 710322-34-2
• 化学式: C₉H₁₃N₃O₂
• 分子量: 195.221
• InChiKey: ZSCDCNNGHVXBRJ-UHFFFAOYSA-N

物化性质

• 沸点：
  363.6±37.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  78.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基5-氨基-2-吡嗪羧酸酯 在 草酰氯 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.33h， 生成 5-[2(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid tert-butoxy-amide
  参考文献：
  名称：

  Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes

  摘要：

  To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.

  DOI：

  10.1021/ml400027y
• 作为产物：
  描述：

  5-氯吡嗪-2-羧酸 在 silver fluoride 作用下， 以 四氢呋喃 、 环己烷 、 乙腈 为溶剂， 反应 16.08h， 生成 2-甲基-2-丙基5-氨基-2-吡嗪羧酸酯
  参考文献：
  名称：

  Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes

  摘要：

  To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.

  DOI：

  10.1021/ml400027y

文献信息

• [EN] 5-SUBSTITUTED-PYRAZINE OR PYRIDINE GLUCOKINASE ACTIVATORS<br/>[FR] ACTIVATEURS DE LA GLUCOKINASE A BASE DE PYRAZINE OU DE PYRIDINE SUBSTITUEES EN POSITION 5
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004052869A1

  公开（公告）日：2004-06-24

  The present invention provides a compound according to formula (I) where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula (I) are also provided, said compounds being glucokinase activators which are useful in the treatment of type II diabetes.

  本发明提供了一种化合物，其化学式为（I），其中取代基的定义在说明书中提供。还提供了包括符合化学式（I）的化合物的药物组合物，这些化合物是葡萄糖激酶激活剂，对于治疗2型糖尿病是有用的。
• 5-Substituted-six-membered heteroaromatic glucokinase activators
  申请人：——

  公开号：US20040147748A1

  公开（公告）日：2004-07-29

  The present invention provides a compound according to formula I 1 where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula I are also provided.

  本发明提供了一种化合物，其化学式为I1，其中取代基的具体说明在规范中提供。还提供了包含化合物I的制药组合物。
• 5-substituted-six-membered heteroaromatic glucokinase activators
  申请人：Hoffmann-La Roche Inc.

  公开号：US07132425B2

  公开（公告）日：2006-11-07

  The present invention provides a compound according to formula I where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula I are also provided.

  本发明提供了一个化合物，其化学式为I，其中置换基的定义在说明书中提供。还提供了包含化学式I的化合物的药物组合物。
• Highly efficient one-pot amination of carboxylate-substituted nitrogen-containing heteroaryl chlorides via Staudinger reaction
  作者：Sachin R. Kandalkar、Rahul D. Kaduskar、Parimi Atchuta Ramaiah、Dinesh A. Barawkar、Debnath Bhuniya、Anil M. Deshpande

  DOI：10.1016/j.tetlet.2012.11.027

  日期：2013.1

  An efficient one-pot method for the synthesis of tert-butyl 6-aminonicotinate (5) is described. The key transformation involves displacement of the chloro group in tert-butyl 6-chloronicotinate (2) with azide followed by a Staudinger reaction. The scope of this methodology is further extended for the synthesis of a series of carboxylate-substituted heteroaryl amines. In particular, we synthesized tert-butyl carboxylate-substituted amino-pyridine, -pyridazine, and -pyrazine. In addition to one-pot conversion, short reaction time, simplicity of operation, ease of purification, and good yields are the key advantages of this methodology. (C) 2012 Elsevier Ltd. All rights reserved.
• AMINODIHYDROTHIAZINE DERIVATIVES SUBSTITUTED WITH CYCLIC GROUPS
  申请人：Shionogi & Co., Ltd.

  公开号：EP2147914B1

  公开（公告）日：2014-06-04