ethyl 4-(5-amino-2-methoxyphenoxy)butanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 4-(5-amino-2-methoxyphenoxy)butanoate
• 英文别名: ethyl 4-(5-amino-2-methoxyphenoxy) butyrate
• 化学式: C₁₃H₁₉NO₄
• 分子量: 253.298
• InChiKey: ZKAMQZNKWKMMCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-(5-amino-2-methoxyphenoxy)butanoate 在 羟胺 、 caesium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 2.0h， 生成 4-{5-[butyl(2-methylquinazolin-4-yl)amino]-2-methoxyphenoxy}-N-hydroxybutanamide
  参考文献：
  名称：

  HISTONE DEACETYLASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF

  摘要：

  本发明涉及一种具有组蛋白去乙酰化酶抑制活性的4-芳氨基喹唑啉羟胺酸化合物、其制备方法、包含该化合物的药物组合物，以及该化合物和药物组合物在制备组蛋白去乙酰化酶抑制剂药物中的用途。本发明的目的是通过药物设计和合成技术，基于优化4-芳氨基喹唑啉的酶表面识别区域和连接区域，获得一系列具有良好低类型选择性和有利药代动力学特性的选择性组蛋白去乙酰化酶抑制剂，从而在提高正常组织或细胞的抗肿瘤活性的同时，减少对正常组织或细胞的影响。

  公开号：

  US20180098990A1
• 作为产物：
  描述：

  2-甲氧基-5-硝基苯酚 在 5%-palladium/activated carbon 、 氢气 、 caesium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 ethyl 4-(5-amino-2-methoxyphenoxy)butanoate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of quinazoline derivatives as dual HDAC1 and HDAC6 inhibitors for the treatment of cancer

  摘要：

  AbstractFifty‐eight quinazoline‐based compounds were designed and synthesized based on the structural optimizations from the lead compound 23bb in an attempt to search for more potent dual HDAC1 and HDAC6 inhibitors. Among them, 32c (HDAC1, IC50 = 31.10 ± 0.37 nM; HDAC6, IC50 = 16.15 ± 0.62 nM) and 32d (HDAC1, IC50 = 37.00 ± 0.24 nM; HDAC6, IC50 = 35.00 ± 0.71 nM) were not only identified as potent dual‐acting HDAC1 and HDAC6 inhibitors with over 10‐fold selectivity to the other HDACs, but also displayed activities in tubulin acetylation and histone H3 acetylation induction. Importantly, both of them displayed strong antiproliferative activities against various tumor cell lines in vitro with IC50 values less than 40 nM, especially for hematologic tumors cells (U266 and RPMI8226, IC50 < 1 nM), which were even better than 23bb and SAHA. Furthermore, 32c showed a significant tumor growth inhibition (antitumor rate = 63.98%, p < 0.05) in the resistant MCF‐7/ADR xenograft model without any obvious body weight changes and abnormal behaviors. Our findings validate that 32c is a potent dual inhibitor of HDAC1/6 that can be an efficacious treatment for breast cancer with Adriamycin resistance.

  DOI：

  10.1111/cbdd.13405

文献信息

• 一种组蛋白去乙酰化酶抑制剂及其制备方法和用途
  申请人：广东众生药业股份有限公司

  公开号：CN106045923A

  公开（公告）日：2016-10-26

  本发明提供一种式I所示化合物或其药物可接受的盐，涉及具有组蛋白去乙酰化酶抑制活性的4‑芳氨基喹唑啉异羟肟酸类的新型化合物、所述化合物的制备方法、包含所述化合物的药物组合物以及所述化合物和药物组合物在制备组蛋白去乙酰化酶抑制剂类药物中的用途；旨在通过药物设计及合成手段获取一系列基于对4‑芳氨基喹唑啉为酶表面识别区及连接区进行优化，具有亚型选择性和良好药代动力学特性的选择性组蛋白去乙酰化酶抑制剂，以提高抗肿瘤活性的同时减少对正常组织或细胞的影响。
• [EN] HISTONE DEACETYLASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF<br/>[FR] INHIBITEUR DE L'HISTONE DÉSACÉTYLASE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 一种组蛋白去乙酰化酶抑制剂及其制备方法和用途
  申请人：GUANGDONG ZHONGSHENG PHARMACEUTICAL CO LTD

  公开号：WO2016146074A1

  公开（公告）日：2016-09-22

  一种式I所示化合物或其药物可接受的盐，其涉及具有组蛋白去乙酰化酶抑制活性的4-芳氨基喹唑啉异羟肟酸类化合物、所述化合物的制备方法、包含所述化合物的药物组合物以及所述化合物和药物组合物在制备组蛋白去乙酰化酶抑制剂类药物中的用途；旨在通过药物设计及合成手段获取一系列基于对4-芳氨基喹唑啉为酶表面识别区及连接区进行优化，具有亚型选择性和良好药代动力学特性的选择性组蛋白去乙酰化酶抑制剂，以提高抗肿瘤活性的同时减少对正常组织或细胞的影响。
• Discovery of Selective Histone Deacetylase 6 Inhibitors Using the Quinazoline as the Cap for the Treatment of Cancer
  作者：Zhuang Yang、Taijin Wang、Fang Wang、Ting Niu、Zhuowei Liu、Xiaoxin Chen、Chaofeng Long、Minghai Tang、Dong Cao、Xiaoyan Wang、Wei Xiang、Yuyao Yi、Liang Ma、Jingsong You、Lijuan Chen

  DOI：10.1021/acs.jmedchem.5b01342

  日期：2016.2.25

  Novel selective histone deacetylase 6 (HDAC6) inhibitors using the quinazoline as the cap were designed, synthesized, and evaluated for HDAC enzymatic assays. N-Hydroxy-4-(2-methoxy-5-(methyl(2-methylquinazolin-4-yl)-amino)phenoxy)butanamide, 23bb, was the most potent selective inhibitor for HDAC6 with an IC50 of 17 nM and showed 25-fold and 200-fold selectivity relative to HDAC1 and HDAC8, respectively. In vitro, 23bb presented low nanomolar antiproliferative effects against panel of cancer cell lines. Western blot analysis further confirmed that 23bb increased acetylation level of a-tubulin in vitro. 23bb has a good pharmacokinetic profile with oral bioavailability of 47.0% in rats. In in vivo efficacy evaluations of colorectal HCT116, acute myelocytic leukemia MV4-11, and B cell lymphoma Romas xenografts, 23bb more effectively inhibited the tumor growth than SAI-IA even at a 4-fold reduced dose or ACY-1215 at the same dose. Our results indicated that 23bb is a potent oral anticancer candidate for selective HDAC6 inhibitor and deserves further investigation.
• 2-Phenyl-substituierte Imidazotriazinone als Phoshodiesterase Inhibitoren
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP1174431B1

  公开（公告）日：2012-05-30
• INDOLIN-2-ONES AND AZA-INDOLIN-2-ONES
  申请人：Diels Gaston Stanislas Marcella

  公开号：US20100190786A1

  公开（公告）日：2010-07-29

  The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumour activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.