LT175

• 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: LT175
• 英文别名: (2S)-2-(biphenyl-4-yloxy)-3-phenylpropanoic acid；(2S)-3-phenyl-2-(4-phenylphenoxy)propanoic acid
• 化学式: C₂₁H₁₈O₃
• 分子量: 318.372
• InChiKey: TZTPJJNNACUQQR-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  LT175 在 氯化亚砜 、 硼烷四氢呋喃络合物 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 (S)-N-{2-[(1,1'-Biphenyl)-4-yloxy]-3-phenylpropyl}-benzenesulfonamide
  参考文献：
  名称：

  A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor Alpha/Gamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c02093
• 作为产物：
  描述：

  D-苯基乳酸甲酯 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 LT175
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling Investigation of New Chiral Fibrates with PPARα and PPARγ Agonist Activity

  摘要：

  Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular diseases, obesity, and diabetes. Medications targeted to PPARs have been established to treat hyper-lipidemia (fibrates) and insulin resistance (glitazones). Thus, there is significant interest in developing new and specific ligands for these receptors. Here, we present the results of the screening of new ligands of PPAR alpha and PPAR gamma. Optical isomers of new chiral fibrates were synthesized and tested in cell-based assays. Compound (S)-7 showed a dual PPARU alpha/gamma activity, and its stereochemistry was crucial in receptor activation. Protease protection experiments suggested that this compound binds directly to PPAR. Moreover, computational studies showed that it properly docks to PPAR alpha and gamma ligand binding pockets. Interestingly, (S)-7 exhibited only a modest capacity to induce the differentiation of murine fibroblasts 3T3-L1 into adipocytes compared to rosiglitazone, a well-known PPAR gamma agonist.

  DOI：

  10.1021/jm0502844

文献信息

• <i>para</i>-Selective arylation and alkenylation of monosubstituted arenes using thianthrene <i>S</i>-oxide as a transient mediator
  作者：Xiao-Yue Chen、Xiao-Xue Nie、Yichen Wu、Peng Wang

  DOI：10.1039/d0cc00641f

  日期：——

  Using thianthrene S-oxide (TTSO) as a transient mediator, para-arylation and alkenylation of mono-substituted arenes have been demonstrated via a para-selective thianthrenation/Pd-catalyzed thio-Suzuki-Miyaura coupling sequence under mild conditions. This reaction features a broad substrate scope, and functional group and heterocycle tolerance. The versatility of this approach was further demonstrated

  使用噻吩硫氧化物（TTSO）作为瞬时介体，单取代的芳烃的对位芳构化和烯基化反应已通过在温和条件下通过对位选择性噻吩化/ Pd催化的硫代-Suzuki-Miyaura偶联序列进行。该反应具有广泛的底物范围，官能团和杂环耐受性。复杂的生物活性支架的后期功能化以及一些药物的直接合成，进一步证明了这种方法的多功能性，包括Tetriprofen，Ibuprofen，Bifonazole和LJ570。
• 对位取代芳基化合物的制备方法
  申请人：中国科学院上海有机化学研究所

  公开号：CN111187130B

  公开（公告）日：2021-12-14

  本发明公开了一种如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，包括以下步骤：惰性气氛下，溶剂中，在碱和钯催化剂的作用下，如式(II)所示的芳基锍盐与如式(III)所示的硼化物进行偶联反应，即可。该方法以单取代芳烃为底物，原位构建芳基锍盐，钯催化剂催化原位构建的芳基锍盐发生Suzuki‑Miyaura偶联反应，快速高效构建单取代芳烃对位芳基化或烯基化产物。该方法条件温和，底物普适性高，杂环偶联底物耐受性广泛。
• AGENTS FOR TREATMENT OF ALCOHOL USE DISORDER
  申请人：Servicio Andaluz de Salud

  公开号：EP3834888A2

  公开（公告）日：2021-06-16

  The present invention relates to the use of PPARα agonist compounds for preventing, alleviating, improving and/or treating alcohol use disorder.

  本发明涉及 PPARα 激动剂化合物在预防、减轻、改善和/或治疗酒精使用障碍方面的用途。
• Crystal Structure of the Peroxisome Proliferator-Activated Receptor γ (PPARγ) Ligand Binding Domain Complexed with a Novel Partial Agonist: A New Region of the Hydrophobic Pocket Could Be Exploited for Drug Design
  作者：Roberta Montanari、Fulvio Saccoccia、Elena Scotti、Maurizio Crestani、Cristina Godio、Federica Gilardi、Fulvio Loiodice、Giuseppe Fracchiolla、Antonio Laghezza、Paolo Tortorella、Antonio Lavecchia、Ettore Novellino、Fernando Mazza、Massimiliano Aschi、Giorgio Pochetti

  DOI：10.1021/jm800733h

  日期：2008.12.25

  The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating glucose and lipid metabolism. The search for new PPAR ligands with reduced adverse effects with respect to the marketed antidiabetic agents thiazolidinediones (TZDs) and the dual-agonists glitazars is highly desired. We report the crystal structure and activity of the two enantiomeric forms of a clofibric acid analogue, respectively complexed with the ligand-binding domain (LBD) of PPAR gamma, and provide an explanation on a molecular basis for their different potency and efficacy against PPAR gamma. The more potent S-enantionier is a dual PPAR alpha/PPAR gamma agonist which presents a partial agonism profile against PPAR gamma. Docking of the S-enantiomer in the PPAR alpha-LBD has been performed to explain its different Subtype pharmacological profile. The hypothesis that partial agonists show differential stabilization of helix 3, when compared to full agonists, is also discussed. Moreover, the structure of the complex with the S-enantiomer reveals a new region of the PPAR gamma-LBD never sampled before by other ligands.
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.