Methyl 3-cyclopentyl-2-(3,4-dichlorophenyl)propanoate | 300356-76-7

• 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: Methyl 3-cyclopentyl-2-(3,4-dichlorophenyl)propanoate
• CAS: 300356-76-7
• 化学式: C₁₅H₁₈Cl₂O₂
• 分子量: 301.213
• InChiKey: RUEVJQIPLJYOIX-UHFFFAOYSA-N

物化性质

• 沸点：
  372.6±27.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Methyl 3-cyclopentyl-2-(3,4-dichlorophenyl)propanoate 、 N-甲基脲 在 magnesium methanolate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以27%的产率得到3-环戊基-2-(3,4-二氯苯基)-N-(甲基氨基甲酰)丙酰胺
  参考文献：
  名称：

  Discovery, Structure−Activity Relationships, Pharmacokinetics, and Efficacy of Glucokinase Activator (2R)-3-Cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675)

  摘要：

  Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SA R development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.

  DOI：

  10.1021/jm100039a
• 作为产物：
  描述：

  碘甲基环戊烷 、 3,4-二氯苯乙酸甲酯 在 六甲基磷酰三胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以29%的产率得到Methyl 3-cyclopentyl-2-(3,4-dichlorophenyl)propanoate
  参考文献：
  名称：

  Discovery, Structure−Activity Relationships, Pharmacokinetics, and Efficacy of Glucokinase Activator (2R)-3-Cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675)

  摘要：

  Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SA R development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.

  DOI：

  10.1021/jm100039a

文献信息

• GLUCOKINASE ACTIVATORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1169312A2

  公开（公告）日：2002-01-09
• US6528543B1
  申请人：——

  公开号：US6528543B1

  公开（公告）日：2003-03-04
• [EN] GLUCOKINASE ACTIVATORS<br/>[FR] ACTIVATEURS DE GLUCOKINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000058293A2

  公开（公告）日：2000-10-05

  The present invention relates to compounds of formula (I) wherein R?1, R2, R3 and R4¿ are as defined in claim 1 and pharmaceutically acceptable salts thereof. The compounds are glucokinase activators which increase insulin secretion in the treatment of type II diabetes.
• Discovery, Structure−Activity Relationships, Pharmacokinetics, and Efficacy of Glucokinase Activator (2<i>R</i>)-3-Cyclopentyl-2-(4-methanesulfonylphenyl)-<i>N</i>-thiazol-2-yl-propionamide (RO0281675)
  作者：Nancy-Ellen Haynes、Wendy L. Corbett、Fred T. Bizzarro、Kevin R. Guertin、Darryl W. Hilliard、George W. Holland、Robert F. Kester、Paige E. Mahaney、Lida Qi、Cheryl L. Spence、John Tengi、Mark T. Dvorozniak、Aruna Railkar、Franz M. Matschinsky、Joseph F. Grippo、Joseph Grimsby、Ramakanth Sarabu

  DOI：10.1021/jm100039a

  日期：2010.5.13

  Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SA R development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.