2-[3-氟-4-(三氟甲基)苯基]-4-甲基-5-氯甲基噻唑 | 317319-33-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[3-氟-4-(三氟甲基)苯基]-4-甲基-5-氯甲基噻唑
• 英文名称: 5-chloromethyl-4-methyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]thiazole
• 英文别名: 5-(chloromethyl)-2-[3-fluoro-4-(trifluoromethyl) phenyl]-4-methylthiazole；5-(Chloromethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazole
• CAS: 317319-33-8
• 化学式: C₁₂H₈ClF₄NS
• 分子量: 309.715
• InChiKey: QZRTZQRCEAOOLW-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷、乙醚、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  2-[3-氟-4-(三氟甲基)苯基]-4-甲基-5-氯甲基噻唑 在 lithium hydroxide 、 caesium carbonate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 16.0h， 生成 2-(4-(((2-(3-氟-4-(三氟甲基)苯基)-4-甲基噻唑-5-基)甲基)硫代)-2-甲基苯氧基)乙酸
  参考文献：
  名称：

  Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)—synthesis and biological activity

  摘要：

  We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00207-5
• 作为产物：
  描述：

  2-[3-氟-4-(三氟甲基)苯基]-4-甲基-5-羟基甲基噻唑 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到2-[3-氟-4-(三氟甲基)苯基]-4-甲基-5-氯甲基噻唑
  参考文献：
  名称：

  Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)—synthesis and biological activity

  摘要：

  We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00207-5

文献信息

• PPARo ACTIVATOR
  申请人：JAPAN SCIENCE AND TECHNOLOGY AGENCY

  公开号：US20220031666A1

  公开（公告）日：2022-02-03

  The present invention provides a PPARδ activator containing a novel PPARδ agonist (peroxisome proliferator-activated receptor δ) as an active ingredient, and an exercise tolerance-improving agent containing the same as an active ingredient. The present invention is a PPARδ activator containing a guanidine derivative or a biguanidine derivative as an active ingredient, wherein the PPARδ activator activates transcriptional activity of PPARδ, and the guanidine derivative and the biguanidine derivative are capable of fitting within a PPARδ ligand binding pocket in a state where a guanidino group or a biguanidino group forms a hydrogen bond with amino acid residues corresponding to each of the 413th histidine, 287th histidine, 253rd threonine and the 437th tyrosine of human PPARδ, among amino acid residues constituting an interior surface of the ligand binding pocket; and is an exercise tolerance-improving agent containing the PPARδ activator as an active ingredient.

  本发明提供了一种含有新型PPARδ激动剂（过氧化物酶体增殖物激活受体δ）的PPARδ激活剂作为有效成分的制剂，以及一种含有该制剂作为有效成分的运动耐力改善剂。本发明是一种PPARδ激活剂，其含有鸟氨酸衍生物或双胍衍生物作为有效成分，其中PPARδ激活剂激活PPARδ的转录活性，而鸟氨酸衍生物和双胍衍生物能够适合于PPARδ配体结合口袋中，当鸟氨酸基团或双胍基团与构成配体结合口袋内表面的每个氨基酸残基中的413号组氨酸、287号组氨酸、253号苏氨酸和437号酪氨酸形成氢键时；并且是一种含有PPARδ激活剂作为有效成分的运动耐力改善剂。
• Selective peroxisome proliferator-activated receptor δ isosteric selenium agonists as potent anti-atherogenic agents in vivo
  作者：Jungwook Chin、Jun Young Hong、Jaehwan Lee、Hoosang Hwang、Hyunsil Ko、Hyukjae Choi、Dongyup Hahn、Jaeyoung Ko、Sang-Jip Nam、Jungae Tak、Jungyeob Ham、Heonjoong Kang

  DOI：10.1016/j.bmcl.2010.10.103

  日期：2010.12

  We report the synthesis and in vivo activity of a novel anti-atherogenic agent, isosteric selenium PPAR delta-selective ligand. This ligand did not cause significant body or liver weight changes and did not have obvious adverse effects on intestinal polyp formation. Our overall results clearly demonstrate that PPAR delta is a viable drug candidate for targeting and treating atherosclerosis. (C) 2010 Elsevier Ltd. All rights reserved.
• [EN] PPARδ ACTIVATOR<br/>[FR] ACTIVATEUR DE PPARδ<br/>[JA] ＰＰＡＲδ活性化剤
  申请人：JAPAN SCIENCE & TECH AGENCY

  公开号：WO2020085393A1

  公开（公告）日：2020-04-30

  本発明は、新規なＰＰＡＲδ（Peroxisome proliferator-activated receptor δ）のアゴニストを有効成分とするＰＰＡＲδ活性化剤、及びこれを有効成分とする運動耐性改善剤を提供する。本発明は、グアニジン誘導体又はビグアニジン誘導体を有効成分とし、ＰＰＡＲδの転写活性を活性化する、ＰＰＡＲδ活性化剤；前記グアニジン誘導体及び前記ビグアニジン誘導体は、グアニジノ基又はビグアニジノ基が、ＰＰＡＲδのリガンド結合ポケットの内部表面を構成するアミノ酸残基のうち、ヒトＰＰＡＲδのＨｉｓ４１３、Ｈｉｓ２８７、Ｔｈｒ２５３、及びＴｙｒ４３７にそれぞれ相当するアミノ酸残基と水素結合をした状態で、前記リガンド結合ポケットの内部に嵌まり込み得る、前記ＰＰＡＲδ活性化剤；並びに、前記いずれかのＰＰＡＲδ活性化剤を有効成分とする、運動耐性改善剤である。
• Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)—synthesis and biological activity
  作者：Marcos L. Sznaidman、Curt D. Haffner、Patrick R. Maloney、Adam Fivush、Esther Chao、Donna Goreham、Michael L. Sierra、Christelle LeGrumelec、H.Eric Xu、Valerie G. Montana、Millard H. Lambert、Timothy M. Willson、William R. Oliver、Daniel D. Sternbach

  DOI：10.1016/s0960-894x(03)00207-5

  日期：2003.5

  We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Synthesis and Evaluation of PPARδ Agonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis
  作者：Brian J. Kress、Dong Hyun Kim、Jared R. Mayo、Jeffery T. Farris、Benjamin Heck、Jeffrey G. Sarver、Divya Andy、Jill A. Trendel、Bruce E. Heck、Paul W. Erhardt

  DOI：10.1021/acs.jmedchem.1c00560

  日期：2021.5.27