(9-Acetyloxy-2-propanoylbenzo[f][1]benzofuran-4-yl) acetate | 1393549-94-4

• 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: (9-Acetyloxy-2-propanoylbenzo[f][1]benzofuran-4-yl) acetate
• CAS: 1393549-94-4
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: VTTRJSPXJSMLBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  82.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carbaldehyde 在 吡啶 、 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 、 锌 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 11.66h， 生成 (9-Acetyloxy-2-propanoylbenzo[f][1]benzofuran-4-yl) acetate
  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

• [EN] NOVEL ESTERS OF 4,9-DIHYDROXY-NAPHTHO[2,3-b]FURANS FOR DISEASE THERAPIES<br/>[FR] NOUVEAUX ESTERS DE 4,9-DIHYDROXY-NAPHTO[2,3-B]FURANNES POUR TRAITEMENT THÉRAPEUTIQUE DE MALADIES
  申请人：ZHOUSHAN HAIZHONGZHOU XINSHENG PHARMACEUTICALS CO LTD

  公开号：WO2012119265A1

  公开（公告）日：2012-09-13

  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。
• US9150530B2
  申请人：——

  公开号：US9150530B2

  公开（公告）日：2015-10-06
• Synthesis and Structure–Activity Relationships of Lapacho Analogues. 1. Suppression of Human Keratinocyte Hyperproliferation by 2-Substituted Naphtho[2,3-<i>b</i>]furan-4,9-diones, Activation by Enzymatic One- and Two-Electron Reduction, and Intracellular Generation of Superoxide
  作者：Alexandra Reichstein、Silke Vortherms、Sven Bannwitz、Jan Tentrop、Helge Prinz、Klaus Müller

  DOI：10.1021/jm3009597

  日期：2012.8.23

  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.