5-methylisoxazole-4-carboxylic acid {5-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]-2-methylphenyl}amide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-methylisoxazole-4-carboxylic acid {5-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]-2-methylphenyl}amide
• 英文别名: N-(5-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-2-methylphenyl)-5-methylisoxazole-4-carboxamide；N-[5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylphenyl]-5-methyl-1,2-oxazole-4-carboxamide
• 化学式: C₂₀H₁₆ClF₃N₄O₃
• 分子量: 452.82
• InChiKey: BMGVHAWWNGXBPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  96.3
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-甲基异恶唑-4-甲酸 在 盐酸 、 氯化亚砜 、 tin(II) chloride dihdyrate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成 5-methylisoxazole-4-carboxylic acid {5-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]-2-methylphenyl}amide
  参考文献：
  名称：

  Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors

  摘要：

  A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most compounds showed selective antiproliferative activity toward the U937 cell line and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor 6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-l-yl)-5-(trifluoromethyl)benzamido)pherwl)isoxazole-4-carboxamide was found to be very potent inhibitor of FMS kinase (GI(50) = 0.016 mu M, IC50 = 9.95 nM) with excellent selectivity profiles and is a promising candidate for further development in therapeutics for cancer. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.031

文献信息

• N-(5-ARYLAMIDO-2-METHYLPHENYL)-5-METHYLISOOXAZOLE-4-CARBOXAMIDE DERAVATIVE, PHARMACEUTICAL ACCEPTABLE SALT THEREOF, METHOD FOR PREPARATION THEROF AND FMS KINASE INHIBITOR COMPRISING THE SAME AS ANACTIVE INGREDIENT
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus

  公开号：US20170273947A1

  公开（公告）日：2017-09-28

  The present invention relates to N-(5-arylamido-2-methylphenyl)-5-methylisoquoxazole-4-carboxamide derivative, or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising same. The compound according to the present invention exhibits an FMS kinase inhibitory activity and thus can be used as pharmaceutical composition for preventing and treating diseases associated therewith.
• US9789086B1
  申请人：——

  公开号：US9789086B1

  公开（公告）日：2017-10-17
• Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors
  作者：Daseul Im、Kyungjin Jung、Songyi Yang、Waqar Aman、Jung-Mi Hah

  DOI：10.1016/j.ejmech.2015.08.031

  日期：2015.9

  A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most compounds showed selective antiproliferative activity toward the U937 cell line and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor 6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-l-yl)-5-(trifluoromethyl)benzamido)pherwl)isoxazole-4-carboxamide was found to be very potent inhibitor of FMS kinase (GI(50) = 0.016 mu M, IC50 = 9.95 nM) with excellent selectivity profiles and is a promising candidate for further development in therapeutics for cancer. (C) 2015 Elsevier Masson SAS. All rights reserved.