5-[[bis[(1,1-dimethylethoxy)carbonyl]]amino]-N-[[[(9H-fluoren-9-yl)methoxy]carbonyl]oxy]-2-pyrazine carboximidamide | 1352212-90-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 5-[[bis[(1,1-dimethylethoxy)carbonyl]]amino]-N-[[[(9H-fluoren-9-yl)methoxy]carbonyl]oxy]-2-pyrazine carboximidamide
• 英文别名: [(Z)-[amino-[5-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]pyrazin-2-yl]methylidene]amino] 9H-fluoren-9-ylmethyl carbonate
• CAS: 1352212-90-8；1427744-21-5
• 化学式: C₃₀H₃₃N₅O₇
• 分子量: 575.621
• InChiKey: SZVRLKRVVFJAKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-[[bis[(1,1-dimethylethoxy)carbonyl]]amino]-N-[[[(9H-fluoren-9-yl)methoxy]carbonyl]oxy]-2-pyrazine carboximidamide 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 7.25h， 生成 (R)-3-chloro-α-(cyclopentylmethyl)-N-[2-[[[[[(9H-fluoren-9-yl)methoxy]carbonyl]oxy]-amino]iminomethyl]-5-pyrazinyl]-4-(methylsulfonyl)benzeneacetamide
  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-[[bis[(1,1-dimethylethoxy)carbonyl]]amino]-2-pyrazinecarbonitrile 在 哌啶 、 盐酸羟胺 作用下， 以 吡啶 、 二甲基亚砜 为溶剂， 反应 1.58h， 生成 5-[[bis[(1,1-dimethylethoxy)carbonyl]]amino]-N-[[[(9H-fluoren-9-yl)methoxy]carbonyl]oxy]-2-pyrazine carboximidamide
  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