5-methoxy-3-(4-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one

• 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: 5-methoxy-3-(4-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: MpPPOX；3-(4-phenoxyphenyl)-5-methoxy-3H-(1,3,4)oxadiazol-2-one；3-(4-Phenoxyphenyl)-5-methoxy-1,3,4-oxadiazol-2-one；5-Methoxy-3-(4-phenoxyphenyl)-1,3,4-oxadiazol-2-one
• 化学式: C₁₅H₁₂N₂O₄
• 分子量: 284.271
• InChiKey: YAKCIFSNRAIAJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 2-(4-phenoxyphenyl)hydrazinecarboxylate 、 氯甲酸三氯甲酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到5-methoxy-3-(4-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  （4-苯氧基苯基）四唑碳酰胺和相关化合物作为脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂酶（MAGL）的双重抑制剂

  摘要：

  脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂酶（MAGL）的抑制剂是参与降解内源性大麻素（如anandamide和2-arachidonoylglycerol）的主要酶，在治疗包括疼痛，炎症和焦虑症在内的多种疾病中具有潜在的用途。 。在本研究中，通过体外测定了八种已知的FAAH和MAGL抑制剂对适当酶的抑制作用的选择性和有效性。在可比较的条件下工作的分析方法。由于许多已知的FAAH和MAGL抑制剂仅由结合了杂环系统的亲脂性支架组成，因此，通过将不同的杂环结构连接到相同的亲脂性骨架（即4-苯氧基苯）上，评估了它们对酶抑制的作用。在此研究中合成的最具活性的化合物之一是N，N-二甲基-5-（4-苯氧基苯基）-2 H-四唑-2-羧酰胺（16）（IC 50 FAAH：0.012μM; IC 50MAGL：0.028μM）。该抑制剂在亲脂性4-苯氧基苯基区域被系统修饰。结构-活性关系研究表明，通过用3-

  DOI：

  10.1016/j.ejmech.2013.01.050

文献信息

• Use of substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadizol-2-ones for inhibiting pancreatic lipase
  申请人：——

  公开号：US20030236288A1

  公开（公告）日：2003-12-25

  The invention relates to a method for inhibiting pancreatic lipase, or the prophylaxis or treatment of obesity or diabetes mellitus of type 1 and 2, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadiazol-2-ones of formula 1: 1 wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, or a prodrug, solvate, pharmacologically acceptable salt or acid addition salt thereof.

  本发明涉及一种用于抑制胰腺脂肪酶，或预防或治疗1型和2型糖尿病或肥胖症的方法，适用于需要的患者，包括向患者投给药理有效量的取代的3-苯基-5-烷氧基-3H-(1,3,4)-恶二唑-2-酮，其化学式为1：1，其中R1、R2、R3、R4和R5如本文所述定义，或其前药、溶剂化物、药理上可接受的盐或酸性加成盐。
• Oxadiazolone derivatives, new promising multi-target inhibitors against M. tuberculosis
  作者：Phuong Chi Nguyen、Vincent Delorme、Anaïs Bénarouche、Alexandre Guy、Valérie Landry、Stéphane Audebert、Matthieu Pophillat、Luc Camoin、Céline Crauste、Jean-Marie Galano、Thierry Durand、Priscille Brodin、Stéphane Canaan、Jean-François Cavalier

  DOI：10.1016/j.bioorg.2018.08.025

  日期：2018.12

  A set of 19 oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against two pathogenic slow-growing mycobacteria, Mycobacterium marinum and Mycobacterium bovis BCG, and the avirulent Mycobacterium tuberculosis (M. tb) mc(2)6230. The encouraging minimal inhibitory concentrations (MIC) values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M. tb growth only with moderated MIC50, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. Of interest, all OX derivatives exhibited very low toxicity towards host macrophages. Among the six potential OXs identified, HPDX, a selective inhibitor of extracellular M. tb growth, was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP, in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.
• Analysis of the discriminative inhibition of mammalian digestive lipases by 3-phenyl substituted 1,3,4-oxadiazol-2(3H)-ones
  作者：Vanessa Point、K.V.P. Pavan Kumar、Sylvain Marc、Vincent Delorme、Goetz Parsiegla、Sawsan Amara、Frédéric Carrière、Gérard Buono、Frédéric Fotiadu、Stéphane Canaan、Julien Leclaire、Jean-François Cavalier

  DOI：10.1016/j.ejmech.2012.10.040

  日期：2012.12

  We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para-PhenoxyPhenyl derivatives, i.e. MmPPOX and MpPPOX) with respect to the inhibition of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine (PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and porcine pancreatic extracts (PPE). All three oxadiazolones displayed similar inhibitory activities on DGL, PLRP2s and hCEH than the FDA-approved anti-obesity drug Orlistat towards the same enzymes. These compounds appeared however to be discriminative of HPL (poorly inhibited) and PPL (fully inhibited). The inhibitory activities obtained experimentally in vitro were further rationalized using in silico molecular docking. In the case of DGL, we demonstrated that the phenoxy group plays a key role in specific molecular interactions within the lipase's active site. The absence of this group in the case of MPOX, as well as its connectivity to the neighbouring aromatic ring in the case of MmPPOX and MpPPOX, strongly impacts the inhibitory efficiency of these oxadiazolones and leads to a significant gain in selectivity towards the lipases tested. The powerful inhibition of PPL, DGL, PLRP2s, hCEH and to a lesser extend HPL, suggests that oxadiazolone derivatives could also provide useful leads for the development of novel and more discriminative inhibitors of digestive lipases. These inhibitors could be used for a better understanding of individual lipase function as well as for drug development aiming at the regulation of the whole gastrointestinal lipolysis process. (C) 2012 Elsevier Masson SAS. All rights reserved.
• SUBSTITUIERTE 3-PHENYL-5-ALKOXI-1,3,4-OXDIAZOL-2-ONE UND IHRE VERWENDUNG ALS LIPASE-HEMMER
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1214302B1

  公开（公告）日：2003-10-29
• VERWENDUNG SUBSTITUIERTER 3-PHENYL-5-ALKOXY-1,3,4-OXDIAZOL-2-ONE ZUR HERSTELLUNG VON ARZNEIMITTELN MIT HEMMENDER WIRKUNG AN DER PANKREATISCHEN LIPASE
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1482929A1

  公开（公告）日：2004-12-08