ethyl (E/Z)-[2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethenyl)phenoxy]acetate | 439134-90-4

• 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: ethyl (E/Z)-[2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethenyl)phenoxy]acetate
• 英文别名: Ethyl [2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethenyl)phenoxy]acetate；ethyl 2-[2-methyl-4-[2-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethenyl]phenoxy]acetate
• CAS: 439134-90-4
• 化学式: C₂₄H₂₂F₃NO₃S
• 分子量: 461.505
• InChiKey: WPPJNZLYGOMVIA-UHFFFAOYSA-N

物化性质

• 沸点：
  550.0±60.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (E/Z)-[2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethenyl)phenoxy]acetate 在 钯 氢气 、 petroleum ether ethyl acetate 作用下， 以 Dioxan ethanol 为溶剂， 反应 6.0h， 生成 ethyl [2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethyl)phenoxy]acetate
  参考文献：
  名称：

  Thia-and oxazoles and their use as ppars activators

  摘要：

  公式（I）的化合物或其药学上可接受的盐和溶剂化物。R1和R2独立地为H或C1-3烷基，m为0-3；X1为NH，NCH3，O，S；R3，R4和R5独立地为H，CH3，CF3，OCH3，烯丙基或卤素；X2为（CR10R11）n，其中n为1或2；R10和R11独立地代表H，氟或C1-16烷基；R26和R27独立地为H，C1-3烷基或R26和R27与它们所连接的碳原子形成3-5成员的环烷基环。R6和R7独立地代表H，氟或C1-16烷基；R9为C1-6烷基或CF3；Y和Z中的一个为N，另一个为S或O；每个R8独立地代表CF3，OCH3，CH3或卤素；y为O，1，2，3，4，5。使用公式（I）的化合物制造用于预防或治疗hPPAR介导的疾病或病况，例如失调脂质血症，综合征X，心力衰竭，高胆固醇血症，心血管疾病，2型糖尿病，1型糖尿病，胰岛素抵抗性高脂血症，肥胖症，厌食症，炎症和厌食症。

  公开号：

  US07196107B2
• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 lithium aluminium tetrahydride 、 sodium hydride 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 31.47h， 生成 ethyl (E/Z)-[2-methyl-4-(2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethenyl)phenoxy]acetate
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• Thia-and oxazoles and their use as ppars activators
  申请人：——

  公开号：US20040102493A1

  公开（公告）日：2004-05-27

  A compound of formula (I) or pharmaceutically acceptable salts and solvates thereof. R 1 and R 2 are independently H or C 1-3 alkyl, m is 0-3; X 1 is NH, NCH 3 , O, S; R 3 , R 4 and R 5 are independently H, CH 3 , CF 3 , OCH 3 , allyl or halogen; X 2 is (CR 10 R 11 )n wherein n is 1 or 2; R 10 and R 11 independently represent H, fluorine or C 1-16 alkyl; R 26 and R 27 are independently H, C 1-3 alkyl or R 26 and R 27 together with the carbon atom to which they are bonded form a 3-5 membered cycloalklyl ring. R 6 and R 7 independently represent H, fluorine or C 1-16 alkyl; R 9 is C 1-6 alkyl or CF 3 ; One of Y and Z is N, the other is S or O; Each R 8 independently represents CF 3 , OCH 3 , CH 3 or halogen; y is O, 1, 2, 3, 4, 5. Use of a compound of formula (I) for the manufacture of a medicament for the prevention or treatment of a hPPAR mediated disease or condition, such as dyslipidemia, syndrome X, heart failure, hypercholesteremia, cardiovascular disease, type II diabetes mellitus, type 1 diabetes, insulin resistance hyperlipidemia, obesity, anorexia bulimia, inflammation and anorexia nervosa. 1

  化合物I的公式或其药学上可接受的盐和溶剂化物。其中，R1和R2分别为H或C1-3烷基，m为0-3；X1为NH，NCH3，O，S；R3、R4和R5分别为H，CH3，CF3，OCH3，烯丙基或卤素；X2为（CR10R11）n，其中n为1或2；R10和R11独立地表示H，氟或C1-16烷基；R26和R27独立地表示H，C1-3烷基或R26和R27与它们结合的碳原子形成3-5环烷基环。R6和R7独立地表示H，氟或C1-16烷基；R9为C1-6烷基或CF3；Y和Z中的一个为N，另一个为S或O；每个R8独立地表示CF3，OCH3，CH3或卤素；y为O，1，2，3，4，5。化合物I的用途是制备用于预防或治疗hPPAR介导的疾病或病况的药物，例如失调脂质血症、综合征X、心力衰竭、高胆固醇血症、心血管疾病、2型糖尿病、1型糖尿病、胰岛素抵抗性高脂血症、肥胖症、厌食症、疼痛和厌食症。
• Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents
  作者：Michael L. Sierra、Véronique Beneton、Anne-Bénédict Boullay、Thierry Boyer、Andrew G. Brewster、Frédéric Donche、Marie-Claire Forest、Marie-Hélène Fouchet、Françoise J. Gellibert、Didier A. Grillot、Millard H. Lambert、Alain Laroze、Christelle Le Grumelec、Jean Michel Linget、Valerie G. Montana、Van-Loc Nguyen、Edwige Nicodème、Vipul Patel、Annie Penfornis、Olivier Pineau、Danig Pohin、Florent Potvain、Géraldine Poulain、Cécile Bertho Ruault、Michael Saunders、Jérôme Toum、H. Eric Xu、Robert X. Xu、Pascal M. Pianetti

  DOI：10.1021/jm058056x

  日期：2007.2.1

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.