dimethylcarbamic acid 6-chloro-3-[3-(ethylsulfonamido)benzyl]-4-methyl-2-oxo-2H-chromen-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 6-chloro-3-[3-(ethylsulfonamido)benzyl]-4-methyl-2-oxo-2H-chromen-7-yl ester
• 英文别名: [6-chloro-3-[[3-(ethylsulfonylamino)phenyl]methyl]-4-methyl-2-oxochromen-7-yl] N,N-dimethylcarbamate
• 化学式: C₂₂H₂₃ClN₂O₆S
• 分子量: 478.953
• InChiKey: ZRGDMPGCJVIALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯间苯二酚 在 tin(II) chloride dihdyrate 、 硫酸 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 25.5h， 生成 dimethylcarbamic acid 6-chloro-3-[3-(ethylsulfonamido)benzyl]-4-methyl-2-oxo-2H-chromen-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

• 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.