2-{2-ethyl-4-[(4-methyl-2-(4-trifluoromethylphenyl)thiazol-5-yl)methylthio]phenoxy}acetic acid | 1268500-56-6

• 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: 2-{2-ethyl-4-[(4-methyl-2-(4-trifluoromethylphenyl)thiazol-5-yl)methylthio]phenoxy}acetic acid
• 英文别名: 2-[2-Ethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid
• CAS: 1268500-56-6
• 化学式: C₂₂H₂₀F₃NO₃S₂
• 分子量: 467.533
• InChiKey: SGJNGRUDNQPAHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  乙基苯酚 在 lithium aluminium tetrahydride 、 水 、 溴 、 caesium carbonate 、 sodium bromide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 7.0h， 生成 2-{2-ethyl-4-[(4-methyl-2-(4-trifluoromethylphenyl)thiazol-5-yl)methylthio]phenoxy}acetic acid
  参考文献：
  名称：

  GW 501516 类似物的合成、生物学评价和分子建模

  摘要：

  制备了 GW 501516 (1) 的 11 种类似物，并在半高通量人类骨骼肌细胞试验中进行了生物学测试。分析测试表明所有类似物都引起油酸的氧化。在最有效的激动剂中，2e（2-{2-乙基-4-[（4-甲基-2-（4-三氟甲基苯基）噻唑-5-基）甲硫基]苯氧基}-2-甲基丙酸）也受到基于荧光素酶的转染试验表明该化合物是 PPARδ 的强效激动剂和 PPARα 的中度激动剂。化合物 2e 与 PPARδ 的对接表明它占据了激动剂结合位点，并表现出与 His323、His449 和 Tyr473 的关键氢键相互作用。

  DOI：

  10.1002/ardp.201000189

文献信息

• Compounds, compositions and treatment of oleoylethanolamide-like modulators of PPARalpha
  申请人：Fu Jin

  公开号：US20050054730A1

  公开（公告）日：2005-03-10

  The present invention provides compounds, compositions, and methods for the treatment of disorders and conditions mediated by PPARα. The invention relates to the surprising discovery that oleoylethanolamide (OEA) is an endogenous high affinity and selective ligand of PPARα. The compounds of the invention include, but are not limited to, specific PPARα agonists sharing the receptor binding properties of OEA and fatty acid alkanolamides and their homologs which also are PPARα agonists. Such OEA-like compounds include, but are not limited to, compounds of the following formula: in which n is from 0 to 5, the sum of a and b can be from 0 to 4; Z is a member selected from the group consisting of —C(O)N(R o )—; —(R o )NC(O)—; —OC(O)—; —(O)CO—; O; NR o ; and S; and wherein R o and R 2 are members independently selected from the group consisting of unsubstituted or unsubstituted alkyl, hydrogen, C 1 -C 6 alkyl, and lower (C 1 -C 6 ) acyl, and wherein up to eight hydrogen atoms are optionally substituted by methyl or a double bond, and the bond between carbons c and d may be unsaturated or saturated, or a pharmaceutically acceptable salt thereof.

  本发明提供了化合物、组合物和方法，用于治疗由PPARα介导的疾病和病症。本发明涉及到一项令人惊讶的发现，即油酰乙醇胺（OEA）是PPARα的内源性高亲和力和选择性配体。本发明的化合物包括但不限于与OEA具有受体结合特性的特定PPARα激动剂，以及脂肪酸烷基醇胺及其同系物，它们也是PPARα激动剂。这样的类OEA化合物包括但不限于以下公式的化合物：其中n为0至5，a和b的总和可以为0至4；Z是从以下群组中选择的成员：—C(O)N(Ro)—；—(Ro)NC(O)—；—OC(O)—；—(O)CO—；O；NRo；和S；Ro和R2是独立选择的成员，选自未取代或未取代的烷基、氢、C1-C6烷基和较低的（C1-C6）酰基的群组，其中最多八个氢原子可以选择性地被甲基或双键取代，且碳c和d之间的键可能是不饱和或饱和的，或其药学上可接受的盐。
• Combination therapy for controlling appetites
  申请人：Piomelli Daniele

  公开号：US20050101542A1

  公开（公告）日：2005-05-12

  The invention provides methods and pharmaceutical compositions for administering a PPARα agonist (e.g., OEA-like agonist, OEA-like compound), an OEA-like appetite reducing compound, or a FAAH inhibitor and a CB1 cannabinoid receptor antagonist to a subject in order to reduce the consumption or ingestion of food, ethanol or other appetizing substances as well as in treating appetency disorders related to the excess consumption of food, ethanol, and other appetizing substances. The combination therapy can also be useful for reducing body fat or body weight and modulating lipid metabolism.

  该发明提供了一种方法和制药组合物，用于给予PPARα激动剂（例如，OEA样激动剂，OEA样化合物），OEA样食欲减少化合物，或FAAH抑制剂和CB1大麻素受体拮抗剂给予受试者，以减少食物、乙醇或其他开胃物质的摄入或摄入量，并治疗与过量摄入食物、乙醇和其他开胃物质相关的食欲紊乱。该联合治疗也可用于减少体脂肪或体重和调节脂质代谢。
• [EN] COMPOUNDS, COMPOSITIONS AND THERAPEUTIC USES OF OLEOYLETHANOLAMIDE-LIKE COMPOUNDS AND MODULATORS OF PPARalpha<br/>[FR] COMPOSES, COMPOSITIONS ET UTILISATIONS THERAPEUTIQUES DE COMPOSES DE TYPE OLEOYLETHANOLAMIDE ET DE MODULATEURS DES PPAR DOLLAR G(A)
  申请人：UNIV CALIFORNIA

  公开号：WO2005002524A2

  公开（公告）日：2005-01-13

  The present invention provides compounds, compositions, and methods for the treatment of disorders and conditions mediated by PPARa. The invention relates to the surprising discovery that oleoylethanolamide (OEA) is an endogenous high affinity and selective ligand of PPARa. The compounds of the invention include, but are not limited to, specific PPARa agonists sharing the receptor binding properties of OEA and fatty acid alkanolamides and their homologs which also are PPARa agonists. Such OEA-like compounds include, but are not limited to, compounds of the following formula: in which n is from 0 to 5, the sum of a and b can be from 0 to 4; Z is a member selected from the group consisting of -C(O)N(Ro) ; (Ro)NC(O) ; OC(O) ; (O)CO ; O; NRo; and S; and wherein Ro and R2 are members independently selected from the group consisting of unsubstituted or unsubstituted alkyl, hydrogen, C1 -C6 alkyl, and lower (C1-C6) acyl, and wherein up to eight hydrogen atoms are optionally substituted by methyl or a double bond, and the bond between carbons c and d may be unsaturated or saturated, or a pharmaceutically acceptable salt thereof.
• Synthesis, Biological Evaluation and Molecular Modeling of GW 501516 Analogues
  作者：Calin C. Ciocoiu、Aina W. Ravna、Ingebrigt Sylte、Trond Vidar Hansen

  DOI：10.1002/ardp.201000189

  日期：2010.11

  Eleven analogues of GW 501516 (1) were prepared and subjected to biological testing in a semi‐high throughput human skeletal muscle cell assay. The assay testing indicated that all analogues elicited oxidation of oleic acid. Among the most potent agonists, 2e (2‐2‐ethyl‐4‐[(4‐methyl‐2‐(4‐trifluoromethylphenyl)thiazol‐5‐yl)methylthio]phenoxy}‐2‐methylpropanoic acid), was also subjected to a luciferase‐based

  制备了 GW 501516 (1) 的 11 种类似物，并在半高通量人类骨骼肌细胞试验中进行了生物学测试。分析测试表明所有类似物都引起油酸的氧化。在最有效的激动剂中，2e（2-2-乙基-4-[（4-甲基-2-（4-三氟甲基苯基）噻唑-5-基）甲硫基]苯氧基}-2-甲基丙酸）也受到基于荧光素酶的转染试验表明该化合物是 PPARδ 的强效激动剂和 PPARα 的中度激动剂。化合物 2e 与 PPARδ 的对接表明它占据了激动剂结合位点，并表现出与 His323、His449 和 Tyr473 的关键氢键相互作用。