5-[[(2R)-oxiran-2-yl]methoxy]-1,3-benzodioxole | 329977-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 5-[[(2R)-oxiran-2-yl]methoxy]-1,3-benzodioxole
• CAS: 329977-77-7
• 化学式: C₁₀H₁₀O₄
• 分子量: 194.187
• InChiKey: YETPZTCSSANWOG-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[[(2R)-oxiran-2-yl]methoxy]-1,3-benzodioxole 在 copper(l) iodide 、 三氟化硼乙醚 、 magnesium sulfate 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.83h， 生成 3-(6-ethoxybenzo[d][1,3]dioxol-5-yl)-6-fluoro-3-(6-(((R)-2-hydroxy-4-methylpent-4-en-1-yl)oxy)benzo[d][1,3]dioxol-5-yl)indolin-2-one
  参考文献：
  名称：

  [EN] NOVEL FUNGAL MODULATORS
  [FR] NOUVEAUX MODULATEURS FONGIQUES

  摘要：

  本发明涉及抑制药物外排泵的化合物、组合物和方法。这些化合物、组合物和方法可用于增强药物外排泵底物的治疗药物的活性，以及用于治疗耐药的疾病或疾病，如微生物感染和癌症。

  公开号：

  WO2022047375A1
• 作为产物：
  描述：

  芝麻酚 、 右旋环氧氯丙烷 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 9.83h， 生成 5-[[(2R)-oxiran-2-yl]methoxy]-1,3-benzodioxole
  参考文献：
  名称：

  手性S-噻吗洛尔衍生物催化β-酮酯的对映选择性α-羟基化

  摘要：

  由β-阻滞剂抑制剂S-噻吗洛尔衍生的芳氧基氨基丙醇有机催化剂的筛选确定了β-酮酯的不对称α-羟基化的最具活性的催化剂。（R）-1-（叔丁基氨基）-3-（3,4,5-三甲氧基苯氧基）丙烷-2-醇（3k）是最有效的衍生物，它使用叔-对映体催化β-酮酸酯的α-羟基化。丁基过氧化氢作为己烷中的氧化剂，以优异的收率和良好的对映选择性（高达96％的收率，88％ee）提供相应的产物。

  DOI：

  10.1016/j.tet.2012.07.003

文献信息

• Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection
  作者：Yao Chen、Yuan Ju、Chungen Li、Tao Yang、Yong Deng、Youfu Luo

  DOI：10.1038/s41429-019-0177-9

  日期：2019.7

  Methicillin-resistant Staphylococcus aureus (MRSA) infections are a significant global health challenge due to the emergence of strains exhibiting resistance to nearly all classes of antibiotics. This necessitates the rapid development of novel antimicrobials to circumvent this critical problem. Screening of compounds based on phenotypes is one of the major strategies for finding new antibiotics at present. Hence, we here performed a phenotypic screening against MRSA and identified NPS-2143 exhibiting activity against MRSA with an MIC value of 16 μg ml−1. In order to discover more potent anti-MRSA agents, a series of derivatives of NPS-2143 were designed and synthesized. The most promising compounds 48 and 49 exhibited favorable antimicrobial activity with an MIC value of 2 μg ml−1.

  耐甲氧西林金黄色葡萄球菌（MRSA）感染是全球健康的一大挑战，因其出现了对几乎所有抗生素类别都具有耐药性的菌株。这迫切要求迅速开发新型抗菌药物以解决这一关键问题。基于表型的化合物的筛选是目前寻找新抗生素的主要策略之一。因此，我们在此对MRSA进行了表型筛选，并鉴定出对MRSA具有活性的NPS-2143，其最小抑菌浓度（MIC）值为16μg/ml。为了发现更有效的抗MRSA药物，我们设计并合成了NPS-2143的一系列衍生物。最有希望的化合物48和49表现出良好的抗菌活性，其MIC值为2μg/ml。
• An oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida auris
  作者：Kali R. Iyer、Kaddy Camara、Martin Daniel-Ivad、Richard Trilles、Sheila M. Pimentel-Elardo、Jen L. Fossen、Karen Marchillo、Zhongle Liu、Shakti Singh、José F. Muñoz、Sang Hu Kim、John A. Porco、Christina A. Cuomo、Noelle S. Williams、Ashraf S. Ibrahim、John E. Edwards、David R. Andes、Justin R. Nodwell、Lauren E. Brown、Luke Whitesell、Nicole Robbins、Leah E. Cowen

  DOI：10.1038/s41467-020-20183-3

  日期：——

  Candida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach to identify a bis-benzodioxolylindolinone (azoffluxin) that synergizes with fluconazole against C. auris. Azoffluxin enhances fluconazole activity through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels. This activity is conserved across most C. auris clades, with the exception of clade III. Azoffluxin also inhibits efflux in highly azole-resistant strains of Candida albicans, another human fungal pathogen, increasing their susceptibility to fluconazole. Furthermore, azoffluxin enhances fluconazole activity in mice infected with C. auris, reducing fungal burden. Our findings suggest that pharmacologically targeting Cdr1 in combination with azoles may be an effective strategy to control infection caused by azole-resistant isolates of C. auris.

  摘要：Candida auris是一种新兴的真菌病原体，对多种药物表现出抗药性，包括最常用的抗真菌药物氟康唑。本研究采用组合筛选方法，发现一种双苯并二恶烷基吲哚酮（azoffluxin），与氟康唑协同作用，对Candida auris具有增强作用。Azoffluxin通过抑制外排泵Cdr1，增加细胞内氟康唑水平，从而增强了氟康唑的活性。这种活性在大多数Candida auris类群中都是保守的，但在III类群中除外。Azoffluxin还抑制高度氮唑类耐药菌株的外排，增加它们对氟康唑的敏感性。此外，azoffluxin在感染Candida auris的小鼠中增强了氟康唑的活性，减少了真菌负担。我们的发现表明，通过药理学的方式靶向Cdr1，结合氮唑类药物可能是控制氮唑类耐药菌株引起感染的有效策略。
• A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27
  作者：Hai-Wei Xu、Shilong Jia、Mengbo Liu、Xiaobo Li、Xia Meng、Xinxin Wu、Lu Yu、Menglin Wang、Cheng-Yun Jin

  DOI：10.1016/j.ejmech.2020.112708

  日期：2020.11

  Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized alpha, beta-unsaturated-delta-lactone based on a natural product Goniothalamin. It induces apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1. Selective inhibition was observed for the proliferation of gastric cancer cell lines MGC803, HGC27 comparing to Human Gastric Mucosal Epithelial Cell Line (GES1). For the first time, CRM1 inhibitor or degrader inducing apoptosis in gastric carcinoma was investigated. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms
  作者：Zhiyang Jiang、Dongmei Shi、Yitong Chen、Huilin Li、Jin'e Wang、Xinrui Lv、Yunjiang Zi、Dongli Wang、Zhijian Xu、Jiaxing Huang、Junfeng Liu、Hongxia Duan

  DOI：10.1016/j.ejmech.2023.115755

  日期：2023.11
• [EN] ALKYLPIPERIDI NYLBENZO [D] ISOXAZOLE DERIVATIVES HAVING PSYCHOTROPIC ACTIVITY, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME, AND A PROCESS FOR THE PREPARATION OF THE ACTIVE INGREDIENT<br/>[FR] DERIVES D'ALKYPIPERIDI NYLBENZO [D] ISOXAZOLE PRESENTANT UNE ACTIVITE PSYCHOTROPE, COMPOSITIONS PHARMACEUTIQUES CONTENANT CES DERNIERS, ET PROCEDE DE PREPARATION DE L'INGREDIENT ACTIF
  申请人：EGYT GYOGYSZERVEGYESZETI GYAR

  公开号：WO2001017993A1

  公开（公告）日：2001-03-15

  The invention refers to novel alkylpiperidinylbenzo[d]isoxazole derivatives of formula (I), pharmaceutical compositions containing the same, and a process for the preparation of the active ingredient. The compounds of the invention exert action on the central nervous system, and have, primarily, psychotropic activity.