(5-methyl-2-phenyl-oxazol-4-ylmethyl)-carbamic acid tert-butyl ester | 501031-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5-methyl-2-phenyl-oxazol-4-ylmethyl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methyl]carbamate
• CAS: 501031-53-4
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: XOHNZSKFRBQBLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-methyl-2-phenyl-oxazol-4-ylmethyl)-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (5-甲基-2-苯基-1,3-噁唑-4-基)甲胺
  参考文献：
  名称：

  Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARα/γ dual agonists, and X-ray crystallographic studies

  摘要：

  A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modi. cations in the binding and activation of PPAR alpha and PPAR gamma was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPAR gamma-ligand-binding domain was obtained and discussed in this report. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.043
• 作为产物：
  描述：

  2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)acetyl azide 、 叔丁醇 以 甲苯 为溶剂， 反应 18.0h， 以2.330 g的产率得到(5-methyl-2-phenyl-oxazol-4-ylmethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARα/γ dual agonists, and X-ray crystallographic studies

  摘要：

  A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modi. cations in the binding and activation of PPAR alpha and PPAR gamma was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPAR gamma-ligand-binding domain was obtained and discussed in this report. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.043

文献信息

• Antidiabetic agents
  申请人：——

  公开号：US20030171377A1

  公开（公告）日：2003-09-11

  The present invention provides compounds of Formula (I): 1 wherein A, X, Q, Y, B, D, Z, and E have any of the values defined in the specification, and pharmaceutically acceptable salt thereof, that are useful as antidiabetic agents. Also disclosed are pharmaceutical compositions comprising one or more compounds of Formula I, processes for preparing compounds of Formula I, and intermediates useful for preparing compounds of Formula I.

  本发明提供了式(I)的化合物： 1 其中A、X、Q、Y、B、D、Z和E具有规范中定义的任何值，以及药用可接受的盐，这些化合物作为抗糖尿病药是有用的。还公开了包含一个或多个式I化合物的药物组合物，制备式I化合物的方法，以及用于制备式I化合物的中间体。
• Oral antidiabetic agents
  申请人：Warner-Lambert Company LLC

  公开号：EP1577305A1

  公开（公告）日：2005-09-21

  The present invention provides compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein:    A is    X is CH2-CH2-O or -CH2CH2CH2-;    Q is    Y is CH2;    Z is absent;    B is H;    D is H, and E is CO2H; that are useful as antidiabetic agents. Also disclosed are pharmaceutical compositions comprising compounds of formula (I).

  本发明提供了式 (I) 的化合物 或其药学上可接受的盐，其中 A 是 X是CH2-CH2-O或-CH2CH2CH2-； Q 是 Y 是 CH2 Z 不存在； B 是 H； D 是 H、 和 E 是 CO2H； 可用作抗糖尿病药物。还公开了包含式（I）化合物的药物组合物。
• Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARα/γ dual agonists, and X-ray crystallographic studies
  作者：Agustin Casimiro-Garcia、Christopher F. Bigge、Jo Ann Davis、Teresa Padalino、James Pulaski、Jeffrey F. Ohren、Patrick McConnell、Christopher D. Kane、Lori J. Royer、Kimberly A. Stevens、Bruce J. Auerbach、Wendy T. Collard、Christine McGregor、Stephen A. Fakhoury、Robert P. Schaum、Hairong Zhou

  DOI：10.1016/j.bmc.2008.03.043

  日期：2008.5

  A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modi. cations in the binding and activation of PPAR alpha and PPAR gamma was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPAR gamma-ligand-binding domain was obtained and discussed in this report. (c) 2008 Elsevier Ltd. All rights reserved.