β-bromo-α-methylbutenolide | 121900-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: β-bromo-α-methylbutenolide
• 英文别名: 3-methyl-4-bromo-5H-furan-2-one；4-bromo-3-methylfuran-2(5H)-one；4-bromo-3-methyl-2(5H)-furanone；3-bromo-4-methyl-2H-furan-5-one
• CAS: 121900-52-5
• 化学式: C₅H₅BrO₂
• 分子量: 176.997
• InChiKey: OASBMEPRZZCXNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  β-bromo-α-methylbutenolide 在 palladium on activated charcoal 四(三苯基膦)钯 、 氢气 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙酸乙酯 为溶剂， 90.0 ℃ 、275.79 kPa 条件下， 生成 (3R,4R)-4-(3,4-difluorophenyl)-3-methyloxolan-2-one
  参考文献：
  名称：

  Design and Synthesis of Highly Potent Benzodiazepine γ-Secretase Inhibitors:  Preparation of (2S,3R)-3-(3,4- Difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]- diazepin-3-yl)butyramide by Use of an Asymmetric Ireland−Claisen Rearrangement

  摘要：

  Novel benzodiazepine-containing gamma-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of alpha-alkyl or aryl and beta-hydroxy or hydroxymethyl substituents was shown to give highly potent compounds. In particular, (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide (34) demonstrated excellent in vitro potency (IC50 = 0.06nM). 34 could also be selectively methylated to give [H-3]-28, which is of use in radioligand binding assays.

  DOI：

  10.1021/jm034058a
• 作为产物：
  描述：

  2,2-二溴-1-甲基环丙烷-1-羧酸 在 silver trifluoroacetate 作用下， 以 2,2,2-三氟乙醇 为溶剂， 以90%的产率得到β-bromo-α-methylbutenolide
  参考文献：
  名称：

  Regiospecific synthesis of cepanolide, a cancer chemoprotective micronutrient found in green onions

  摘要：

  The naturally occurring gamma-hydroxy-beta-sulfanylbutenolide cepanolide and a range of new analogues were synthesized in concise, regiospecific manner through the combined use of 2-silyloxyfuran oxyfunctionalization and tandem thio-Michael addition/elimination. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.04.007

文献信息

• [EN] INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL<br/>[FR] INHIBITEURS DU CANAL POTASSIQUE MÉDULLAIRE EXTERNE RÉNAL
  申请人：MERCK SHARP & DOHME

  公开号：WO2014015495A1

  公开（公告）日：2014-01-30

  The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

  本发明提供了式I的化合物及其药学上可接受的盐，这些化合物是ROMK（Kir1.1）通道的抑制剂。这些化合物可用作利尿剂和/或钠利尿剂，并用于治疗和预防包括高血压、心力衰竭以及与过多盐分和水分潴留有关的疾病等医疗状况。
• Discovery of MK-8153, a Potent and Selective ROMK Inhibitor and Novel Diuretic/Natriuretic
  作者：Jinlong Jiang、Fa-Xiang Ding、Xiaoyan Zhou、Thomas J. Bateman、Shuzhi Dong、Xin Gu、Reynalda Keh deJesus、Barbara Pio、Haifeng Tang、Harry R. Chobanian、Dorothy Levorse、Mengwei Hu、Brande Thomas-Fowlkes、Michael Margulis、Martin Koehler、Adam Weinglass、Jack Gibson、Kevin Houle、Joel Yudkovitz、Caryn Hampton、Lee-Yuh Pai、Koppara Samuel、Timothy Cutarelli、Kathleen Sullivan、Emma R. Parmee、Ian Davies、Alexander Pasternak

  DOI：10.1021/acs.jmedchem.1c00406

  日期：2021.6.10

  A renal outer medullary potassium channel (ROMK, Kir1.1) is a putative drug target for a novel class of diuretics with potential for treating hypertension and heart failure. Our first disclosed clinical ROMK compound, 2 (MK-7145), demonstrated robust diuresis, natriuresis, and blood pressure lowering in preclinical models, with reduced urinary potassium excretion compared to the standard of care diuretics

  肾外髓质钾通道（ROMK，Kir1.1）是一类新型利尿剂的推定药物靶点，具有治疗高血压和心力衰竭的潜力。我们首次公开的临床 ROMK 化合物2 (MK-7145) 在临床前模型中表现出强效利尿、利尿和降低血压，与护理利尿剂标准相比，尿钾排泄减少。然而，2预计人类半衰期很短（~5 小时），这可能需要比每天一次更频繁地给药。此外，较短的半衰期会产生较高的峰谷比，这可能会引起过度的峰利尿作用，这是与呋塞米等袢利尿剂相关的常见问题。这份报告描述了一种新的 ROMK 抑制剂的发现22e (MK-8153)，具有更长的预计人类半衰期（~14 小时），这将导致峰谷比降低，有可能推断出更广泛和更好耐受的利尿作用。
• Benzodiazepine derivatives as app modulators
  申请人：——

  公开号：US20040082572A1

  公开（公告）日：2004-04-29

  A novel class of 1,4- and 1,5-benzodiazepines of formula (I) is disclosed. The compounds modulate the processing of amyloid precursor protein by &ggr;-secretase, and hence find use in the treatment or prevention of conditions associated with the deposition of &bgr;-amyloid, such as Alzheimer's disease. 1

  公开了一种式(I)的新型1,4-和1,5-苯二氮平类化合物。这些化合物调节&ggr;-分泌酶对淀粉样前体蛋白的加工作用，因此可用于治疗或预防与&bgr;-淀粉样蛋白沉积相关的疾病，如阿尔茨海默病。
• A New, Highly Stereoselective Synthesis of β-Unsubstituted (<i>Z</i>)<i>-</i>γ-Alkylidenebutenolides Using Bromine as a Removable Stereocontrol Element
  作者：John Boukouvalas、Paola Beltrán、Nicolas Lachance、Sébastien Côté、François Maltais、Martin Pouliot

  DOI：10.1055/s-2007-968004

  日期：2007.2

  Several β-unsubstituted (Z)-γ-alkylidenebutenolides have been prepared in highly stereocontrolled fashion by implementing a steric directing group stratagem in the vinylogous aldol condensation of butenolides with aldehydes. Applications to the synthesis of the antitumor heptene (S)-melodorinol and a thiophenelactone from Chamaemelum nobile L. are described.

  通过在烯丙基缩醛与醛的缩合反应中引入空间位阻基团，以高度立体控制的方式制备了几种β-未取代（Z）-γ-烯丙基丁烯醇。本文介绍了将这种方法应用于合成抗肿瘤庚烯（S）-美洛多林和来自夏枯草的噻吩内酯。
• 4-Azidotetronic Acids: A New Class of Azido Derivatives
  作者：E. M. Beccalli、E. Erba、P. Trimarco

  DOI：10.1080/00397910008087364

  日期：2000.2

  4-Azidotetronic derivatives bearing different substituent groups on the carbon atom in position 3 were easily obtained by reaction of the corresponding 4-bromotetronic compounds with sodium azide in methanol at room temperature.