(S)-3-{4-[2-(2-Phenyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy propionic acid | 401789-88-6

• 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: (S)-3-{4-[2-(2-Phenyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy propionic acid
• 英文别名: rac-3-{4-[2-(2-Phenyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy-propionic Acid；2-Methyl-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid；2-methyl-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-phenoxypropanoic acid
• CAS: 401789-88-6
• 化学式: C₂₈H₂₇NO₅
• 分子量: 457.526
• InChiKey: JSTSZHVRXHMZQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-{2-[2-(3-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenyl)-2-methyl-2-phenoxypropionic Acid Ethyl Ester 、 (S)-3-{4-[2-(2-Phenyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy propionic acid 生成 3-(4-{2-[2-(3-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenyl)-2-methyl-2-phenoxypropionic Acid
  参考文献：
  名称：

  Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists

  摘要：

  由以下结构式（I）表示的化合物及其药用可接受的盐、溶剂合物和水合物，其中：n为2、3或4，W为CH2、CH（OH）、C（O）或O；R1为未取代或取代的芳基、杂环芳基、环烷基、杂环烷基、芳基-烷基、杂环芳基-烷基、环烷基-烷基或叔丁基；R2为H、烷基、卤代烷基或苯基；Y为未取代或取代的噻吩-2,5-二基或苯基；R3为烷基或卤代烷基；R4为取代或未取代的苯基、萘基、1,2,3,4-四氢萘基、喹啉基、吡啶基或苯并[1,3]二氧杂环-5-基团；R5为H、烷基或氨基烷基；用于调节过氧化物酶增殖物激活受体，特别是在糖尿病治疗中。

  公开号：

  US20040097590A1
• 作为产物：
  描述：

  2-（5-甲基-2-苯基1，3-氧杂醇-4-烷基）乙酸 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 硼烷 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-3-{4-[2-(2-Phenyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy propionic acid
  参考文献：
  名称：

  Conversion of human-selective PPARα agonists to human/mouse dual agonists: a molecular modeling analysis

  摘要：

  To understand the species selectivity in a series of a-methyl-a-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARalpha leads to the species-specific divergence in ligand binding. Insights obtained in the molecular modeling studies of these key interactions resulted in the ability to convert a human-selective PPARalpha agonist to a human and mouse dual agonist within the same platform.(C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.031

文献信息

• Design and Synthesis of α-Aryloxy-α-methylhydrocinnamic Acids:  A Novel Class of Dual Peroxisome Proliferator-Activated Receptor α/γ Agonists
  作者：Yanping Xu、Christopher J. Rito、Garret J. Etgen、Robert J. Ardecky、James S. Bean、William R. Bensch、Jacob R. Bosley、Carol L. Broderick、Dawn A. Brooks、Samuel J. Dominianni、Patric J. Hahn、Sha Liu、Dale E. Mais、Chahrzad Montrose-Rafizadeh、Kathy M. Ogilvie、Brian A. Oldham、Mary Peters、Deepa K. Rungta、Anthony J. Shuker、Gregory A. Stephenson、Allie E. Tripp、Sarah B. Wilson、Leonard L. Winneroski、Richard Zink、Raymond F. Kauffman、James R. McCarthy

  DOI：10.1021/jm0342616

  日期：2004.5.1

  The design and synthesis of the dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist (S)-2-methyl-3-[4-[2-(5-methyl-2-thiophen-2-yl-oxazol-4-yl)ethoxy]phenyl]-2-pheno xypropionic acid (2) for the treatment of type 2 diabetes and associated dyslipidemia are described. 2 possesses a potent dual hPPAR alpha/gamma agonist profile (IC(50) = 28 and 10 nM; EC(50) = 9 and 4 nM, respectively

  双过氧化物酶体增殖物激活受体（PPAR）α/γ激动剂（S）-2-甲基-3- [4- [2-（5-甲基-2-噻吩-2-基-恶唑-4）的设计与合成描述了用于治疗2型糖尿病和相关血脂异常的（-基）乙氧基]苯基] -2-苯氧基丙酸（2）。2具有有效的双重hPPARα/γ激动剂特性（对于hPPARalpha和hPPARgamma，IC（50）= 28和10 nM； EC（50）= 9和4 nM）。在临床前模型中，2可显着改善胰岛素敏感性，并有效逆转糖尿病性高血糖症，同时显着改善总体脂质体内平衡。
• [EN] OXAZOLYL-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS<br/>[FR] DÉRIVÉS D'ACIDE OXAZOLYL-ARYLPROPIONIQUE ET LEUR UTILISATION COMME AGONISTES DES PPAR
  申请人：LILLY CO ELI

  公开号：WO2002016331A1

  公开（公告）日：2002-02-28

  Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: n is 2, 3, or 4 and W is CH2, CH(OH), C(O) or O; R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl-alkyl, or t-butyl; R2 is H, alkyl, haloalkyl or phenyl; Y is an unsubstituted or substituted thiophen-2,5-diyl or phenylene; R3 is alkyl or haloalkyl; R4 is a substituted or unsubstituted phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, quinolyl, pyridyl or benzo[1,3]dioxol-5-yl group; and R5 is H, alkyl, or aminoalkyl; are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

  以下结构式(I)所代表的化合物及其药学上可接受的盐、溶剂化物和水合物，其中：n为2、3或4，W为CH2、CH(OH)、C(O)或O；R1为未取代或取代的芳基、杂环芳基、环烷基、杂环烷基、芳基烷基、杂环芳基烷基、环烷基烷基或叔丁基；R2为H、烷基、卤代烷基或苯基；Y为未取代或取代的噻吩-2,5-二基或苯基；R3为烷基或卤代烷基；R4为取代或未取代的苯基、萘基、1,2,3,4-四氢萘基、喹啉基、吡啶基或苯并[1,3]二噁烷-5-基团；R5为H、烷基或氨基烷基；在调节过氧化物酶体增殖物激活受体方面有用，特别是在糖尿病治疗中。
• Peroxisome proliferator activated receptor agonists
  申请人：Brooks Alisa Dawn

  公开号：US20050245584A1

  公开（公告）日：2005-11-03

  Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: n is 2, 3, or 4 and W is CH 2 , CH(OH), C(O) or O; R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl-alkyl, or t-butyl; R2 is H, alkyl, haloalkyl or phenyl; Y is an unsubstituted or substituted thiophen-2,5-diyl or phenylene; R3 is alkyl or haloalkyl; R4 is a substituted or unsubstituted phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, quinolyl, pyridyl or benzo[1,3]dioxol-5-yl group; and R5 is H, alkyl, or aminoalkyl; are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

  以下结构式（I）表示的化合物及其药学上可接受的盐、溶剂合物和水合物，其中：n为2、3或4，W为CH2、CH（OH）、C（O）或O；R1为未取代或取代的芳基、杂芳基、环烷基、杂环烷基、芳基-烷基、杂芳基-烷基、环烷基-烷基或叔丁基；R2为H、烷基、卤代烷基或苯基；Y为未取代或取代的噻吩-2,5-二基或苯基；R3为烷基或卤代烷基；R4为取代或未取代的苯基、萘基、1,2,3,4-四氢萘基、喹啉基、吡啶基或苯并[1,3]二噁烷-5-基团；R5为H、烷基或氨基烷基；对于调节过氧化物酶体增殖物活化受体尤其在糖尿病治疗中有用。
• OXAZOLYL-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1313716A1

  公开（公告）日：2003-05-28
• US6930120B2
  申请人：——

  公开号：US6930120B2

  公开（公告）日：2005-08-16