2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide | 710321-33-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide
• 英文别名: (2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-N-[5-(3-hydroxyprop-1-ynyl)pyrazin-2-yl]propanamide
• CAS: 710321-33-8
• 化学式: C₂₂H₂₄ClN₃O₄S
• 分子量: 461.969
• InChiKey: BFPODEUMNZELOT-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2(R)-(3-chloro-4-methylsulfonyl-phenyl)-3-cyclopentylpropionic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 甲苯 为溶剂， 生成 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide
  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。
• 5-SUBSTITUTED-PYRAZINE OR -PYRIDINE GLUCOKINASE ACTIVATORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1572670A1

  公开（公告）日：2005-09-14
• US7132425B2
  申请人：——

  公开号：US7132425B2

  公开（公告）日：2006-11-07