4-Methyl-3-phenoxy-benzoic acid methyl ester | 137960-09-9

• 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: 4-Methyl-3-phenoxy-benzoic acid methyl ester
• 英文别名: Methyl 4-methyl-3-phenoxybenzoate
• CAS: 137960-09-9
• 化学式: C₁₅H₁₄O₃
• 分子量: 242.274
• InChiKey: CJIXFVKHCMFJJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Methyl-3-phenoxy-benzoic acid methyl ester 在 水 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl)-3-phenoxybenzamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC INHIBITORS OF PCSK9
  [FR] INHIBITEURS HÉTÉROCYCLIQUES DE PCSK9

  摘要：

  这种应用涉及可能作为PCSK9的抑制剂或以其他方式调节PCSK9活性的化合物，或其药用可接受的盐、溶剂化合物、前药或多型体，以及包含这些化合物的组合物和配方，以及使用和制备这些化合物的方法。化合物包括式(I)的化合物：(I)其中A、D和Q如本文所述。

  公开号：

  WO2018165718A1
• 作为产物：
  描述：

  甲基丙烯酸苯酯 在 对苯二酚 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 生成 4-Methyl-3-phenoxy-benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis of Functionalized Aryloxy 1,3-Butadienes and Their Transformation to Diaryl Ethers via Diels-Alder Cycloaddition Reactions

  摘要：

  The Diels-Alder reaction involving cycloaddition of aryloxy-substituted 1,3-butadienes with appropriate acetylenic electrophiles, followed by aromatization of the newly formed cyclohexadiene ring, has been used for the synthesis of diaryl ethers. The functionalized aryloxy 1,3-butadienes employed in this study were prepared by either of two methods: (1) methylenation of aryl esters via the Tebbe or related reagents, and (2) from 1-(aryloxy)-2-propanone by a sequence of formylation or alkylthio methlylenation, and subsequent enolsilylation. A tetrasubstituted butadiene containing two phenoxy groups at the 1 and 3 positions also was prepared by the latter method. The cycloaddition reactions of 2,3-dioxy-substituted dienes occurred in high yield, but, as expected, with no regioselectivity to furnish nearly equal mixtures of regioisomeric cycloadducts. In contrast, application of 1,2,3-trihetero-substituted dienes resulted in regiospecific cycloaddition reactions. Transformation of the cyclohexadiene cycloadducts to an aromatic ring was accomplished by dehydrogenation with DDQ or by elimination during the cycloaddition process of a molecule of an alkyl mercaptan. A chiral acetylenic ketone derived from D- or L-serine underwent condensation, without racemization, with aryloxy dienes to provide diaryl ethers related to the isodityrosine antibiotics.

  DOI：

  10.1021/jo00124a010

文献信息

• Synthesis of oxazolidine derivatives of β-[3-(aryloxy)aryl]-α-amino acids by application of the diels-alder reaction
  作者：Richard K. Olsen、Xianqi Feng

  DOI：10.1016/s0040-4039(00)93539-1

  日期：1991.10

  The Diels-Alder reaction has been used to construct the diaryl ether unit in oxazolidine derivatives of β-[3-(aryloxy)aryl]-α-amino acids. Cycloaddition of acetylenic ketone 6 with substituted aryloxy dienes, and subsequent aromatization, provided the title compounds in good yields. Reaction of 6 with Danishefsky's diene furnished optically pure derivatives of L-tyrosine.

  Diels-Alder反应已经用于在β-[3-（芳氧基）芳基]-α-氨基酸的恶唑烷衍生物中构建二芳基醚单元。炔基酮6与取代的芳氧基二烯的环加成反应，以及随后的芳构化，以高收率提供了标题化合物。6与Danishefsky's diene的反应提供了光学纯的L-酪氨酸衍生物。
• [EN] AMINOCOUMARIN COMPOUNDS AND METHODS OF THEIR USE<br/>[FR] COMPOSÉS D'AMINOCOUMARINE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：HARVARD COLLEGE

  公开号：WO2019178119A1

  公开（公告）日：2019-09-19

  Disclosed are aminocoumarin compounds, pharmaceutical compositions containing aminocoumarin compounds, and methods of their use, e.g., in the treatment of a Gram- negative bacterial infection.

  公开了氨基香豆素化合物、含有氨基香豆素化合物的药物组合物，以及它们的使用方法，例如在治疗革兰氏阴性细菌感染中的应用。
• Heterocyclic inhibitors of PCSK9
  申请人：CARDIO THERAPEUTICS PTY LTD

  公开号：US11091466B2

  公开（公告）日：2021-08-17

  This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include comprising of Formula (I): (I) wherein A, D and Q are described herein.

  本申请涉及可作为 PCSK9 抑制剂或以其他方式调节 PCSK9 活性的化合物，或其药学上可接受的盐、溶液剂、原药或多晶型物，还涉及包含此类化合物的组合物和制剂，以及使用和制造此类化合物的方法。化合物包括式（I）：(I) 其中 A、D 和 Q 如本文所述。
• A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove
  作者：Benny J. Evison、James T. Palmer、Gilles Lambert、Herbert Treutlein、Jun Zeng、Brice Nativel、Kévin Chemello、Qing Zhu、Jie Wang、Yanfen Teng、Wei Tang、Yanfeng Xu、Anuj Kumar Rathi、Sanjay Kumar、Alexandra K. Suchowerska、Jasneet Parmar、Ian Dixon、Graham E. Kelly、James Bonnar

  DOI：10.1016/j.bmc.2020.115344

  日期：2020.3

  Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use. The advent of an orally bioavailable small molecule inhibitor of the PCSK9-LDLR interaction is an attractive alternative, however efforts have been tempered as the binding interface is unfavourable for binding by small organic molecules. Despite its challenging nature, we report herein the discovery of compound 3f as a small molecule inhibitor of PCSK9. The kinase inhibitor nilotinib emerged from a computational screen that was applied to identify compounds that may bind to a cryptic groove within PCSK9 and proximal to the LDLR-binding interface. A subsequent in vitro PCSK9-LDLR binding assay established that nilotinib was a bona fide but modest inhibitor of the interaction (IC50 = 9.8 mu M). Through multiple rounds of medicinal chemistry, 3f emerged as a lead-like molecule by demonstrating disruption of the PCSK9-LDLR interaction at nanomolar levels in vitro (IC50 = 537 nM) with no inhibitory activity (IC50 > 10 mu M) against a small panel of kinases. Compound 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. Most significantly, compound 3f lowered total cholesterol levels in the plasma of wild-type mice, thereby providing proof-of-concept that the notion of a small molecule inhibitor against PCSK9 is therapeutically viable.
• HETEROCYCLIC INHIBITORS OF PCSK9
  申请人：Cardio Therapeutics Pty Ltd

  公开号：EP3609882B1

  公开（公告）日：2022-07-13