1-(3-cyclopentyl-2-phenyl-propionyl)-3-methyl-urea | 300354-51-2

• 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: 1-(3-cyclopentyl-2-phenyl-propionyl)-3-methyl-urea
• 英文别名: 3-cyclopentyl-N-(methylcarbamoyl)-2-phenylpropanamide
• CAS: 300354-51-2
• 化学式: C₁₆H₂₂N₂O₂
• 分子量: 274.363
• InChiKey: BSKWDMIUUDRESB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-环戊基-2-苯基丙酸甲酯 、 N-甲基脲 在 magnesium methanolate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以62%的产率得到1-(3-cyclopentyl-2-phenyl-propionyl)-3-methyl-urea
  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

• Urea derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US06528543B1

  公开（公告）日：2003-03-04

  Glucokinase activating compounds of the formula wherein R1 and R2 are independently hydrogen, halo, amino, nitro, cyano, sulfonamido, lower alkyl, perfluoro-lower alkyl, lower alkyl thio, perfluoro-lower alkyl thio, lower alkyl sulfonyl, or perfluoro-lower alkyl sulfonyl; R3 is cycloalkyl having from 3 to 7 carbon atoms or lower alkyl having from 2 to 4 carbon atoms; R4 is hydrogen, lower alkyl, lower alkenyl, hydroxy lower alkyl, halo lower alkyl, R5 and R6 are hydrogen or lower alkyl; and n is 0, 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof

  该公式中的激活葡萄糖激酶化合物，其中R1和R2独立地为氢、卤素、氨基、硝基、氰基、磺酰胺基、低碳基、全氟低碳基、低碳硫基、全氟低碳硫基、低碳基磺酰基或全氟低碳基磺酰基；R3为具有3至7个碳原子的环烷基或具有2至4个碳原子的低碳基；R4为氢、低碳基、低碳烯基、羟基低碳基或卤素低碳基；R5和R6为氢或低碳基；n为0、1、2、3或4；或其药学上可接受的盐。
• 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.