dimethylcarbamic acid 3-(2-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-chlomen-7-yl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: dimethylcarbamic acid 3-(2-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-chlomen-7-yl ester
• 英文别名: [3-[(2-aminophenyl)methyl]-6-chloro-4-methyl-2-oxochromen-7-yl] N,N-dimethylcarbamate
• 化学式: C₂₀H₁₉ClN₂O₄
• 分子量: 386.835
• InChiKey: ACXODBAODQZCHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 2-(2-nitrobenzyl)-3-oxobutanoate 在 tin(II) chloride dihdyrate 、 硫酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 20.5h， 生成 dimethylcarbamic acid 3-(2-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-chlomen-7-yl ester
  参考文献：
  名称：

  The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors

  摘要：

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.001

文献信息

• p27 Protein Inducer
  申请人：Sakai Toshiyuki

  公开号：US20110009398A1

  公开（公告）日：2011-01-13

  The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G 1 , G 2 , G 3 and G 8 are each independently selected from —N═ etc., Ring G 6 is selected from divalent aryl etc., A is selected from amino etc., G 4 is selected from oxygen etc., G 5 is selected from oxygen etc., G 7 is selected from —CH 2 — etc., and R 2 is selected from C 1-6 alkyl etc.

  本发明提供了一种p27蛋白诱导剂，其包含以下通式（11）所表示的化合物或其药学上可接受的盐作为活性成分：其中G1，G2，G3和G8各自独立地选择自—N═等，环G6选择自双价芳基等，A选择自氨基等，G4选择自氧等，G5选择自氧等，G7选择自—CH2—等，R2选择自C1-6烷基等。
• p27 PROTEIN INDUCER
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2172198A1

  公开（公告）日：2010-04-07

  The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G1, G2, G3 and G8 are each independently selected from -N= etc., Ring G6 is selected from divalent aryl etc., A is selected from amino etc., G4 is selected from oxygen etc., G5 is selected from oxygen etc., G7 is selected from -CH2- etc., and R2 is selected from C1-6 alkyl etc.

  本发明提供了一种 p27 蛋白诱导剂，其活性成分包括下式（11）所代表的化合物或其药学上可接受的盐： 其中G1、G2、G3和G8各自独立地选自-N＝等，环G6选自二价芳基等，A选自氨基等，G4选自氧等，G5选自氧等，G7选自-CH2-等，R2选自C1-6烷基等。
• US8569378B2
  申请人：——

  公开号：US8569378B2

  公开（公告）日：2013-10-29
• The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors
  作者：Toshihiro Aoki、Ikumi Hyohdoh、Noriyuki Furuichi、Sawako Ozawa、Fumio Watanabe、Masayuki Matsushita、Masahiro Sakaitani、Kazutomo Ori、Kenji Takanashi、Naoki Harada、Yasushi Tomii、Mitsuyasu Tabo、Kiyoshi Yoshinari、Yuko Aoki、Nobuo Shimma、Hitoshi Iikura

  DOI：10.1016/j.bmcl.2013.10.001

  日期：2013.12

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.