5-[(4-benzyloxy-3-methoxyphenyl)methylidene]-2,4-thiazolidinedione | 911714-25-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[(4-benzyloxy-3-methoxyphenyl)methylidene]-2,4-thiazolidinedione
• 英文别名: 5-(4-Benzyloxy-3-methoxy-benzylidene)-thiazolidine-2,4-dione；(5Z)-5-[4-(benzyloxy)-3-methoxybenzylidene]-1,3-thiazolidine-2,4-dione；(5Z)-5-[(3-methoxy-4-phenylmethoxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 911714-25-5
• 化学式: C₁₈H₁₅NO₄S
• 分子量: 341.387
• InChiKey: ZMPONXGAPWHWCS-YBEGLDIGSA-N

物化性质

• 熔点：
  221-223 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 密度：
  1.345±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[(4-benzyloxy-3-methoxyphenyl)methylidene]-2,4-thiazolidinedione 、 4-叔丁基苄溴 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以83%的产率得到5-{(Z)-1-[4-(benzyloxy)-3-methoxyphenyl]methylidene}-3-[4-(tert-butyl)benzyl]-1,3-thiazolane-2,4-dione
  参考文献：
  名称：

  Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is an extracellular enzyme that hydrolyzes lysophosphatidylcholine (LPC) to produce the lipid mediator lysophosphatidic acid (LPA). The ATX LPA signaling axis has been implicated in diverse physiological and pathological processes, including vascular development, inflammation, fibrotic disease, and tumor progression. Therefore targeting ATX with small molecule inhibitors is an attractive therapeutic strategy. We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optimization of boronic acid based ATX inhibitors. The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC50 = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use.

  DOI：

  10.1021/jm1005012
• 作为产物：
  描述：

  氯化苄 在 哌啶 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 125.0 ℃ 、1.38 MPa 条件下， 反应 25.25h， 生成 5-[(4-benzyloxy-3-methoxyphenyl)methylidene]-2,4-thiazolidinedione
  参考文献：
  名称：

  Synthesis, biological activity and structure–activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells

  摘要：

  Insulin resistance is a complex altered metabolic condition characterized by impaired insulin signaling and implicated in the pathogenesis of serious human diseases, such as diabetes, obesity, neurodegenerative pathologies. In pursuing our aim to identify new agents able to improve cellular insulin sensitivity, we have synthesized new 4-[(5-arylidene-4-oxo-2-phenylimino/oxothiazolidin-3-yl)methyl] benzoic acids (5, 8) and evaluated their inhibitory activity towards human protein tyrosine phosphatases PTP1B, LMW-PTP and TCPTP, enzymes which are involved in the development of insulin resistance. Compounds 5 and 8 showed from moderate to significant selectivity toward PTP1B over both the highly homologous TCPTP and the two isoforms of human LMW-PTP. In addition, most of the tested compounds selectively inhibited LMW-PTP IF1 over the isoform IF2. Docking studies into the active sites of PTP1B and LMW-PTP aided the rationalization of the observed PTP inhibitory profile. Moreover, most tested compounds were capable to induce the insulin metabolic pathway in mouse C2C12 skeletal muscle cells by remarkably stimulating both IR beta phosphorylation and 2-deoxyglucose cellular uptake. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.11.001

文献信息

• Use of estrogen related receptor-modulating aryl ethers
  申请人：Player R. Mark

  公开号：US20060014812A1

  公开（公告）日：2006-01-19

  Therapeutic methods of using certain heterocyclic arylidene aryl ether compounds for treating diseases or disorders mediated through modulation of estrogen related receptor alpha are described.

  使用某些杂环芳基亚醛基芳醚化合物的治疗方法，用于治疗通过调节雌激素相关受体α介导的疾病或疾病。
• Synthesis, in vitro, in silico and in vivo hypoglycemic and lipid-lowering effects of 4-benzyloxy-5-benzylidene-1,3-thiazolidine-2,4-diones mediated by dual PPAR α/γ modulation
  作者：José Luis Madrigal-Angulo、Carlos Ménez-Guerrero、Samuel Estrada-Soto、Juan José Ramírez-Espinosa、Julio César Almanza-Pérez、Ismael León-Rivera、Emanuel Hernández-Núñez、Yoshajandith Aguirre-Vidal、Carlos D. Flores-León、Rodrigo Aguayo-Ortíz、Gabriel Navarrete-Vazquez

  DOI：10.1016/j.bmcl.2022.128804

  日期：2022.8
• ARYLIDENES FOR THE TREATMENT OF ESTROGEN RELATED RECEPTOR-ALPHA MEDIATED DISEASES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1781271A1

  公开（公告）日：2007-05-09
• [EN] THIAZOLIDINE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF METABOLIC BONE DISORDERS<br/>[FR] DERIVES DE THIAZOLIDINE UTILES POUR LE TRAITEMENT ET LA PREVENTION DE TROUBLES METABOLIQUES DES OS
  申请人：ROCHE DIAGNOSTICS GMBH

  公开号：WO2000018746A1

  公开（公告）日：2000-04-06

  The object of the present invention are compounds of general formula (I), in which: m signifies a number between 0-8; q signifies a number between 0-8; A signifies a single or double bond; R1 signifies hydrogen or, when X and Z are oxygen, also -(CH2)-COR4 with a =0-6; R2, R3 signify hydrogen or lower alkyl, whereby R2 and R3 can be the same or different and, when m signifies 2-8, R2 and R3 in the group CR2=CR3 can have various significances within the following sequence; R4 signifies hydroxyl, lower alkoxy or the NR1R2 residue, whereby R1 and R2 can be the same or different; X signifies oxygen or imino; Z signifies oxygen, sulfur or imino; W signifies an optionally mono- or polysubstituted saturated or unsaturated mono-, bi- or tricycle which can contain one or more hetero atoms, as well as their physiologically compatible salts, esters, optically active forms, racemates, tautomers, as well as derivatives which can be metabolized in vivo to compounds of general formula (I), as well as the use of these compounds for the production of medicaments for the prophylaxis or therapy of metabolic bone disorders.
• [EN] ARYLIDENES FOR THE TREATMENT OF ESTROGEN RELATED RECEPTOR-ALPHA MEDIATED DISEASES<br/>[FR] ARYLIDÈNES POUR LE TRAITEMENT DE MALADIES INDUITES PAR ALPHA-RÉCEPTEUR D'ESTROGÈNE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006019741A1

  公开（公告）日：2006-02-23

  Therapeutic methods of using certain heterocyclic arylidene aryl ether compounds for treating diseases or disorders mediated through modulation of estrogen related receptor alpha are described.