(S)-3-(3-Chloro-4-hydroxy-phenyl)-2-methoxy-propionic acid ethyl ester | 477980-80-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (S)-3-(3-Chloro-4-hydroxy-phenyl)-2-methoxy-propionic acid ethyl ester
• 英文别名: (2S)-3-(3-Chloro-4-hydroxy-phenyl)-2-methoxy-propionic acid ethyl ester；ethyl (2S)-3-(3-chloro-4-hydroxyphenyl)-2-methoxypropanoate
• CAS: 477980-80-6
• 化学式: C₁₂H₁₅ClO₄
• 分子量: 258.702
• InChiKey: ZKQAHCCVWUKVSJ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(3-Chloro-4-hydroxy-phenyl)-2-methoxy-propionic acid ethyl ester 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-3-{4-[3-(4-Benzoyl-phenoxy)-propoxy]-3-chloro-phenyl}-2-methoxy-propionic acid
  参考文献：
  名称：

  2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents

  摘要：

  Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.042
• 作为产物：
  描述：

  ethyl (S)-2-methoxy-3-(4-hydroxyphenyl)propanoate 在 N-氯代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 以62%的产率得到(S)-3-(3-Chloro-4-hydroxy-phenyl)-2-methoxy-propionic acid ethyl ester
  参考文献：
  名称：

  2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents

  摘要：

  Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.042

文献信息

• Modulators of peroxisome proliferator activated receptors
  申请人：Brooks Alisa Dawn

  公开号：US20050020684A1

  公开（公告）日：2005-01-27

  Disclosed is a compound represented by Structural Formula (I): Ar is a substituted or unsubstituted aromatic group. Q is a covalent bond, —CH 2 — or —CH 2 CH 2 —; W is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene linking group from two to ten atoms in length, preferably from two to seven atoms in length. Phenyl Ring A is optionally substituted with up to four substituents in addition to R 1 and W, R 2 is (CH 2 ) n —CH(OR 2 )—(CH 2 ) n E, —(CH)═C(OR 2 )—(CH 2 ) n E, —(CH 2 ) n —CH(Y)—(CH 2 ) m E or (CH)═C(Y)(CH 2 ) m E; wherein E is COOR 3 , C 1 -C 3 alkylnitrile, carboxamide, sulfonamide, acylsulfonamide or tetrazole and wherein sulfonamide, acylsulfonamide and tetrazole are optionally substituted with one or more substituents independently selected from: C 1 -C 6 alkyl, haloalkyl and aryl-C o - 4 -alkyl; R 2 is H, an aliphatic group, a substituted aliphatic group, haloalkyl, an aromatic group, a substituted aromatic group, —COR 4 , —COOR 4 , —CONR 5 R 6 , —C(S)R 4 , —C(S)OR 4 or C(S)NR 5 R 6 , R 3 is H, an aliphatic group, a substituted aliphatic group, an aromatic group or a substituted aromatic group. Y is O—, CH 2 —, CH 2 CH 2 — or CH═CH— and is bonded to a carbon atom in Phenyl Ring A that is ortho to R 1 . R 4 -R 6 are independently H, an aliphatic group, a substituted aliphatic group, an aromatic group or a substituted aromatic group. n and m are independently 0, 1 or 2.

  本发明公开了一种由结构式（I）表示的化合物：其中Ar是取代或未取代的芳香基团。Q是共价键，-CH2-或-CH2CH2-; W是取代或未取代的烷基或取代或未取代的异烷基连接基，长度为两到十个原子，优选长度为两到七个原子。苯环A可选地与R1和W以外的最多四个取代基取代，R2是（CH2）n-CH（OR2）-（CH2）nE，-（CH）=C（OR2）-（CH2）nE，-（CH2）n-CH（Y）-（CH2）mE或（CH）=C（Y）（CH2）mE;其中E是COOR3，C1-C3烷基腈，羧酰胺，磺酰胺，酰基磺酰胺或四唑，磺酰胺，酰基磺酰胺和四唑可选地与一个或多个取代基取代，独立地选自：C1-C6烷基，卤代烷基和芳基-Co-4-烷基; R2是H，脂肪基，取代脂肪基，卤代烷基，芳基，取代芳基，-COR4，-COOR4，-CONR5R6，-C（S）R4，-C（S）OR4或C（S）NR5R6，R3是H，脂肪基，取代脂肪基，芳基或取代芳基。Y是O-，CH2-，CH2CH2-或CH═CH-，并与Phenyl环A中与R1相邻的碳原子键合。R4-R6独立地是H，脂肪基，取代脂肪基，芳基或取代芳基。n和m独立地为0、1或2。
• US7192982B2
  申请人：——

  公开号：US7192982B2

  公开（公告）日：2007-03-20
• 2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents
  作者：José A. Martín、Dawn A. Brooks、Lourdes Prieto、Rosario González、Alicia Torrado、Isabel Rojo、Beatriz López de Uralde、Carlos Lamas、Rafael Ferritto、María Dolores Martín-Ortega、Javier Agejas、Francisco Parra、John R. Rizzo、Gary A. Rhodes、Roger L. Robey、Charles A. Alt、Samuel R. Wendel、Tony Y. Zhang、Anne Reifel-Miller、Chahrzad Montrose-Rafizadeh、Joseph T. Brozinick、Eric Hawkins、Elizabeth A. Misener、Daniel A. Briere、Robert Ardecky、James D. Fraser、Alan M. Warshawsky

  DOI：10.1016/j.bmcl.2004.10.042

  日期：2005.1

  Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes. (C) 2004 Elsevier Ltd. All rights reserved.