2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester | 343322-32-7

• 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-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester
• 英文别名: 2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester；Ethyl 2-methyl-2-[4-[[[4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbonyl]amino]methyl]phenoxy]propanoate
• CAS: 343322-32-7
• 化学式: C₂₅H₂₂F₆N₂O₄S
• 分子量: 560.517
• InChiKey: JMMTVCHYBGDKFC-UHFFFAOYSA-N

物化性质

• 密度：
  1.348±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid
  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
• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 lithium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester
  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

• [EN] SUBSTITUTED OXAZOLES AND THIAZOLES DERIVATIVES AS HPPAR ALPHA ACTIVATORS<br/>[FR] DERIVES D'OXAZOLES ET DE THIAZOLES SUBSTITUES EN TANT QU'ACTIVATEURS HPPAR (RECEPTEUR ACTIVE DE PROLIFERATION DU PERIXOSOME HUMAIN) ALPHA
  申请人：GLAXO GROUP LTD

  公开号：WO2001040207A1

  公开（公告）日：2001-06-07

  A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof wherein; X1 represents O or S; R?1 and R2¿ independently represent H, halogen, -CH¿3? and -OCH3; n represents 1 or 2; X2 represents NH, NCH3 or O; One of Y and Z is N, and the other is O or S; R?3¿ represents phenyl or pyridyl (wherein the N is in position 2 or 3) and is optionally substituted by one or more halogen, NO¿2?, NH2, CF3, OCF3, OC1-6 straight or branched alkyl, C1-6 straight or branched alkyl, alkenyl or alkynyl with the provision that when R?3¿ is pyridyl, the N is unsubstituted; R4 represents CF¿3? or CH3.

  化合物的公式（I）及其药学上可接受的盐、溶剂合物和可水解酯，其中：X1代表O或S；R?1和R2¿独立地代表H，卤素，-CH¿3?和-OCH3；n代表1或2；X2代表NH，NCH3或O；Y和Z中的一个是N，另一个是O或S；R?3¿代表苯基或吡啶基（其中N位于2或3位），并且可以被一个或多个卤素，NO¿2？ ，NH2，CF3，OCF3，OC1-6直链或支链烷基，C1-6直链或支链烷基，烯基或炔基取代，但当R?3¿为吡啶基时，N未被取代；R4代表CF¿3？或CH3。
• SUBSTITUTED OXAZOLES AND THIAZOLES DERIVATIVES AS HPPAR ALPHA ACTIVATORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1244642A1

  公开（公告）日：2002-10-02
• US6518290B1
  申请人：——

  公开号：US6518290B1

  公开（公告）日：2003-02-11
• 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.