2-(2-methyl-4-(1-(4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)-2-phenylethylthio)phenoxy)acetic acid | 591775-42-7

• 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: 2-(2-methyl-4-(1-(4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)-2-phenylethylthio)phenoxy)acetic acid
• 英文别名: 2-[2-Methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-2-phenylethyl]sulfanylphenoxy]acetic acid
• CAS: 591775-42-7
• 化学式: C₂₈H₂₄F₃NO₃S₂
• 分子量: 543.631
• InChiKey: UHZSDVNOWGZQIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  647.7±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-(氯甲基)-4-甲基-2-[4-(三氟甲基)苯基]-1,3-噻唑 在 咪唑 、 四丁基氟化铵 、 异丙基氯化镁 、 potassium carbonate 、 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 13.67h， 生成 2-(2-methyl-4-(1-(4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)-2-phenylethylthio)phenoxy)acetic acid
  参考文献：
  名称：

  Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor δ agonists as potent anti-obesity agents in vivo

  摘要：

  We have discovered and demonstrated the in vitro and in vivo PPAR delta-selective activity of novel Y-shaped agonists. These compounds activated hPPAR delta with EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPAR delta agonists with 10(4)-fold selectivity over the other two subtypes, namely, hPPAR alpha and hPPAR gamma. The PPAR delta ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.055

文献信息

• [EN] PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RECEPTEUR ACTIVE DU PROLIFERATEUR DES PEROXYSOMES
  申请人：LILLY CO ELI

  公开号：WO2003072100A1

  公开（公告）日：2003-09-04

  The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts thereof, Formula I: (Formula I); wherein: (a) R5 is selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkenyl, aryl (C0-C4) alkyl, aryloxy (C0-C4) alkyl, arylthio (C0-C4) alkyl, and further wherein when R5 is alkyl, R5 can optionally combine with W to form a 6 membered cycloheteroalkyl ring that is fused with the oxazole or thiazole ring to which the R5 group is attached; (b) R9 is selected from the group consisting of C1-C5 alkyl, C1-C5 alkenyl, and arylC0-C3alkyl; (c) T1 is selected from the group consisting of C and N; (d) W is selected from the group consisting of CH2, C(O)N(R21), N(R21), N(R21)CH2, O, OCH2, S, and SO2; and(e) X is selected from the group consisting of C, CH2C, and CCH2.

  本发明涉及以下结构式所表示的化合物及其药学上可接受的盐，公式I：（公式I）;其中：（a）R5选自（C1-C6）烷基，（C1-C6）烯基，芳基（C0-C4）烷基，芳氧基（C0-C4）烷基，芳硫基（C0-C4）烷基，进一步地，当R5是烷基时，R5可以选择与W结合形成一个6元环杂环烷基环，该环与R5基固定的噁唑或噻唑环融合；（b）R9选自C1-C5烷基，C1-C5烯基和芳基C0-C3烷基；（c）T1选自C和N的群；（d）W选自CH2，C（O）N（R21），N（R21），N（R21）CH2，O，OCH2，S和SO2的群；（e）X选自C，CH2C和CCH2的群。
• Peroxisome proliferator activated receptor modulators
  申请人：Conner Eugene Scott

  公开号：US20050107449A1

  公开（公告）日：2005-05-19

  The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts thereof, Formula I. (Formula I); wherein: (a) R5 is selected from the group consisting of (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, aryl (C 0 -C 4 ) alkyl, aryloxy (C 0 -C 4 ) alkyl, arylthio (C 0 -C 4 ) alkyl, and further wherein when R5 is alkyl, R5 can optionally combine with W to form a 6 membered cycloheteroalkyl ring that is fused with the oxazole or thiazole ring to which the R5 group is attached; (b) R9 is selected from the group consisting of C 1 -C 5 alkyl, C 1 -C 5 alkenyl, and arylC 0 -C 3 alkyl. (c) T 1 is selected from the group consisting of C and N, (d) W is selected from the group consisting of CH 2 , C(O)N(R21), N(R21), N(R21)CH 2 , O, OCH 2 , S, and SO 2 ; and (e) X is selected from the group consisting of C, CH 2 C, and CCH 2

  本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，式I（式I）; 其中：（a）R5选自由（C1-C6）烷基，（C1-C6）烯基，芳基（C0-C4）烷基，芳氧基（C0-C4）烷基，芳硫基（C0-C4）烷基组成的群体，此外，当R5为烷基时，R5可以选择性地与W结合，形成与R5基固定的噁唑或噻唑环融合的6元环杂环烷基环; （b）R9选自由C1-C5烷基，C1-C5烯基和芳基C0-C3烷基组成的群体；（c）T1选自由C和N组成的群体；（d）W选自由CH2，C（O）N（R21），N（R21），N（R21）CH2，O，OCH2，S和SO2组成的群体；（e）X选自由C，CH2C和CCH2组成的群体。
• USE OF THE FETAL REPROGRAMMING OF A PPAR AGONIST
  申请人：SNU R & DB Foundation

  公开号：EP2612669A2

  公开（公告）日：2013-07-10

  The present invention relates to a novel use of a PPAR δ agonist, and more particularly, to a fetal reprogramming effect of a PPAR δ agonist. According to the present invention, a PPAR δ agonist adjusts calcium ion during embryo genesis and a early fetal development period to increase slow muscle fiber and to thus improve muscle endurance, thereby improving lipid and glucose metabolism and reprogramming the metabolism of the entire body, thus preventing/inhibiting the occurrence of metabolic diseases, such as obesity and diabetes in an adult body caused by a high-fat diet and a lack of exercise, and improving memory for an adult. In addition, fetal reprogramming using a PPAR δ agonist prevents/inhibits the occurrence of diabetes in a mouse model for diabetes. Therefore, the PPAR δ agonist may be used in a pharmaceutical composition for enhancing the endurance of a human and an animal by embryonic/fetal reprogramming, preventing/inhibiting metabolic diseases such as obesity, diabetes, arteriosclerosis and fatty liver, and enhancing memory. The PPAR δ agonist may also be used in a nutritional supplement for pregnant women, in food additives, in a functional food supplement or functional beverage composition, in pharmaceutical compositions for animals, in an endurance enhancer for animals, in dry milk and baby formula compositions, in an animal feed composition, etc.

  本发明涉及 PPAR δ 激动剂的一种新用途，更具体地说，涉及 PPAR δ 激动剂的一种胎儿重编程效应。根据本发明，PPAR δ 激动剂可在胚胎形成期和胎儿发育早期调节钙离子，增加慢肌纤维，从而提高肌肉耐力，进而改善脂质和葡萄糖代谢，对整个身体的新陈代谢进行重编程，从而预防/抑制成人身体因高脂肪饮食和缺乏运动而导致的肥胖和糖尿病等代谢疾病的发生，并改善成人的记忆力。此外，使用 PPAR δ 激动剂进行胎儿重编程可预防/抑制糖尿病小鼠模型中糖尿病的发生。因此，PPAR δ 激动剂可用于药物组合物中，通过胚胎/胎儿重编程增强人和动物的耐力，预防/抑制代谢性疾病，如肥胖、糖尿病、动脉硬化和脂肪肝，以及增强记忆力。PPAR δ 激动剂还可用于孕妇营养补充剂、食品添加剂、功能性食品补充剂或功能性饮料组合物、动物药物组合物、动物耐力增强剂、干奶和婴儿配方组合物、动物饲料组合物等。
• PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR MODULATORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1480640B1

  公开（公告）日：2007-08-15
• Thiazole Compound (as PPAR delta) Ligand and Pharmaceutical, Cosmetic and Health Food Comprised Thereof
  申请人：Kang Heonjoong

  公开号：US20100041723A1

  公开（公告）日：2010-02-18

  The present invention relates to a thiazole compound as a peroxisome proliferator activated receptor δ (PPARδ) activator or pharmaceutically acceptable salts thereof, and a pharmaceutical composition, a functional cosmetic composition, a health food, health beverages, a food additive and animal feeds containing the same.