2-propionylnaphtho[2,3-b]furan-4,9-dione | 1393549-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 2-propionylnaphtho[2,3-b]furan-4,9-dione
• 英文别名: 2-Propanoylbenzo[f][1]benzofuran-4,9-dione；2-propanoylbenzo[f][1]benzofuran-4,9-dione
• CAS: 1393549-79-5
• 化学式: C₁₅H₁₀O₄
• 分子量: 254.242
• InChiKey: OHWWOWBPRZNFRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  BOC-甘氨酸 、 2-propionylnaphtho[2,3-b]furan-4,9-dione 在 四丁基溴化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以40.8%的产率得到2-propionyl-4,9-bis{[(tert-butoxycarbonyl)amino]acetoxy}naphtho[2,3-b]furan
  参考文献：
  名称：

  [EN] NOVEL ESTERS OF 4,9-DIHYDROXY-NAPHTHO[2,3-b]FURANS FOR DISEASE THERAPIES
  [FR] NOUVEAUX ESTERS DE 4,9-DIHYDROXY-NAPHTO[2,3-B]FURANNES POUR TRAITEMENT THÉRAPEUTIQUE DE MALADIES

  摘要：

  本发明公开了4,9-二羟基萘并[2,3-b]呋喃的酯类及其制造和使用方法。本发明还公开了将这些酯转化为体内治疗活性4,9-二羟基萘并[2,3-b]呋喃的方法。本发明进一步公开了包含4,9-二羟基萘并[2,3-b]呋喃的酯类的药物组合物，用于治疗包括增殖性疾病在内的各种疾病。

  公开号：

  WO2012119265A1
• 作为产物：
  描述：

  4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carbaldehyde 在 喹啉 、 正丁基锂 、 sodium dithionite 、 copper chromite 、 四丁基溴化铵 、 水 、 双氧水 、 溶剂黄146 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 10.66h， 生成 2-propionylnaphtho[2,3-b]furan-4,9-dione
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Lapacho Analogues. 1. Suppression of Human Keratinocyte Hyperproliferation by 2-Substituted Naphtho[2,3-b]furan-4,9-diones, Activation by Enzymatic One- and Two-Electron Reduction, and Intracellular Generation of Superoxide

  摘要：

  A series of linearly anellated lapacho quinone analogues substituted at the 2-position of the tricyclic naphtho-[2,3-b]furan-4,9-dione system were synthesized and evaluated for their ability to suppress keratinocyte hyperproliferation using HaCaT cells as the primary test system. While very good in vitro potency with IC50 values in the submicromolar range was attained with electron-withdrawing substituents, some compounds were found to induce plasma membrane damage, as evidenced by the release of LDH activity from cytoplasm of the keratinocytes. The most potent analogue against keratinocyte hyperproliferation was the 1,2,4-oxadiazole 18, the potency of which was combined with comparably low cytotoxic membrane damaging effects. Structure-activity relationship studies with either metabolically stable or labile analogues revealed that the quinone moiety was required for activity. Selected compounds were studied in detail for their capability to generate superoxide radicals both in isolated enzymatic one- and two-electron reduction assays as well as in a HaCaT cell-based assay.

  DOI：

  10.1021/jm3009597

文献信息

• NIS-Induced Enone Difunctionalization for the Synthesis of Naphtho[2,3-<i>b</i> ]furan-4,9-diones
  作者：Yun Liu、Wen-Hui Ge、You-Quan Zhu、Hua-You Hu、Hui Fan、Yan-Hui Shi、Hui Wu

  DOI：10.1002/ejoc.201601291

  日期：2017.1.18

  3-b]furan-4,9-diones has been developed by N-iodosuccinimide (NIS)-induced enone difunctionalization with 2-hydroxy-1,4-naphthoquinones. This reaction involved sequential Michael addition, intramolecular oxidative cyclization and dehydrogenative aromatization to form new C–C and C–O bonds at the α and β positions of the enones. Various enones survived under the reaction conditions and the corresponding products

  萘并[2,3-b]呋喃-4,9-二酮的有效合成已通过N-碘代琥珀酰亚胺（NIS）诱导的烯酮双官能化与2-羟基-1,4-萘醌进行合成。该反应涉及连续的迈克尔加成、分子内氧化环化和脱氢芳构化，以在烯酮的 α 和 β 位置形成新的 C-C 和 C-O 键。各种烯酮在反应条件下幸存下来，并以中等至优异的收率获得相应的产物。
• Synthesis, Biological Evaluation and Molecular Docking of Avicequinone C Analogues as Potential Steroid 5α-Reductase Inhibitors
  作者：Wiranpat Karnsomwan、Ponsawan Netcharoensirisuk、Thanyada Rungrotmongkol、Wanchai De-Eknamkul、Supakarn Chamni

  DOI：10.1248/cpb.c16-00727

  日期：——

  Avicequinone C (5a), a furanonaphthoquinone isolated from the Thai mangrove Avicennia marina has been shown previously to have interesting steroid 5α-reductase type 1 inhibitory activity. In this study, a series of avicequinone C analogues containing furanonaphthoquinone with different degrees of saturation and substituents at the furan ring were synthesized. The resulting synthetic avicequinone C and analogues

  从泰国红树林Avicennia滨海分离的呋喃萘醌Avicequinone C（5a）先前已显示出具有令人感兴趣的类固醇5α-还原酶1型抑制活性。在这项研究中，合成了一系列的呋喃萘醌C的类似物，其中的呋喃并萘醌具有不同的饱和度和在呋喃环上的取代基。评估了合成的阿维醌C和类似物（5a-f）以及一些相关化合物，包括2,5-二羟基-1,4-苯醌（6）和天然萘醌，例如Lawone（7a）和Lapachol（7b）人角质形成细胞（HaCaT）的培养细胞系的体外细胞生存力和类固醇5α-还原酶1型抑制活性。基于细胞的生物测定是基于使用非放射性高性能薄层色谱法（HPTLC）直接检测酶促产物二氢睾丸激素（2）进行的。在该系列的呋喃萘醌中，在呋喃环上具有丙酸酯取代基的5e具有比原始分离的化合物5a强约22倍的效价。然而，没有呋喃基序的化合物如6、7a和b不能抑制类固醇5α-还原酶的活性。
• NOVEL ESTERS OF 4, 9-DIHYDROXY-NAPHTHO [2, 3-b] FURANS FOR DISEASE THERAPIES
  申请人：Jiang Zhiwei

  公开号：US20130345176A1

  公开（公告）日：2013-12-26

  The present invention discloses esters of 4,9-dihydroxy-naphtho[2,3-b]furans and methods of making and using the same. The present invention also discloses conversion of the esters into therapeutically active 4,9-dihydroxy-naphtho[2,3-b]furans in vivo. The present invention furthermore discloses pharmaceutical compositions comprising the esters of 4,9-dihydroxy-naphtho[2,3-b]furans for the treatment of various indications including proliferative diseases.

  本发明公开了4,9-二羟基萘并[2,3-b]呋喃的酯类及其制造和使用方法。本发明还公开了将这些酯转化为体内治疗活性4,9-二羟基萘并[2,3-b]呋喃的方法。本发明进一步公开了包含4,9-二羟基萘并[2,3-b]呋喃的酯类的药物组合物，用于治疗包括增殖性疾病在内的各种疾病。
• [EN] TREATMENT OF CANCERS RELATED TO CHRONICALLY ACTIVE RAS<br/>[FR] TRAITEMENT DE CANCERS ASSOCIÉS À UN GÈNE RAS CHRONIQUEMENT ACTIF
  申请人：HANGZHOU YIER BIOTECH CO LTD

  公开号：WO2017079864A1

  公开（公告）日：2017-05-18

  The present invention discloses that naphthofuranquinones and dihydroxynaphthofurans, and derivatives thereof, such as a compound of formula I or II, are effective in deactivating chronically active Ras. The present invention also discloses a method of treating or preventing cancer comprising steps of: 1) identifying a patient suffering from or susceptible to a cancer related to chronically active Ras; and 2) administering a therapeutically effective amount of a compound of formula I or II, or a pharmaceutically acceptable salt thereof. The present invention further discloses a method of treating or preventing cancer comprising steps of: 1) identifying a patient suffering from or susceptible to a cancer related to a K-Ras mutation; and 2) administering a therapeutically effective amount of a compound of formula I or II, or a pharmaceutically acceptable salt thereof.

  本发明揭示了萘呋喹醌和二羟基萘呋喃及其衍生物，例如公式I或II的化合物，在去活化慢性活性Ras方面具有有效性。本发明还揭示了一种治疗或预防癌症的方法，包括以下步骤：1）识别患有或易感患有与慢性活性Ras相关的癌症的患者；和2）给予公式I或II的化合物或其药学上可接受的盐的治疗有效量。本发明还揭示了一种治疗或预防癌症的方法，包括以下步骤：1）识别患有或易感患有与K-Ras突变相关的癌症的患者；和2）给予公式I或II的化合物或其药学上可接受的盐的治疗有效量。
• NOVEL ANTICANCER AGENT
  申请人：Kyoto Pharmaceutical Industries, Ltd.

  公开号：EP3153508A1

  公开（公告）日：2017-04-12

  The problem of the present invention is to provide a useful prodrug compound of a naphthofuran compound. The present invention relates to a compound represented by the formula (IA): [wherein each symbol is as described in the DESCRIPTION] or a pharmaceutically acceptable salt thereof.

  本发明的问题是提供一种有用的萘呋喃化合物原药化合物。本发明涉及一种由式（IA）表示的化合物： [其中各符号如说明书所述]或其药学上可接受的盐。