3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

• 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: 3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine
• 英文别名: 3-hydroxy-N-1-hydroxypropan-2-yl)-5-4-phenoxyphenylamino)isothiazole-4-carboximidamide；N'-(1-hydroxypropan-2-yl)-3-oxo-5-(4-phenoxyanilino)-1,2-thiazole-4-carboximidamide
• 化学式: C₁₉H₂₀N₄O₃S
• 分子量: 384.459
• InChiKey: QDWSVWMOWVHELW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苯氧苯基异硫氰酸盐 在 氢氧化钾 、 溴 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine
  参考文献：
  名称：

  Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors

  摘要：

  The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyanifine group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.048

文献信息

• Phenylamino isothiazole carboxamidines as MEK inhibitors
  申请人：Abdellaoui Hassan

  公开号：US20060194802A1

  公开（公告）日：2006-08-31

  The invention concerns compounds which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted-3-hydroxy-5-arylamino-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)-ones.

  这项发明涉及抑制MEK并具有抗肿瘤活性的化合物。这些化合物包括N-取代-3-羟基-5-芳基氨基异噻唑-4-甲酰胺。还包括互变异噻唑-3(2H)-酮。
• PHENYLAMINO ISOTHIAZOLE CARBOXAMIDINES AS MEK INHIBITORS
  申请人：Abdellaoui Hassan

  公开号：US20080306063A1

  公开（公告）日：2008-12-11

  The invention concerns compounds which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted-3-hydroxy-5-arylamino-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)-ones.

  本发明涉及抑制MEK并具有抗肿瘤活性的化合物，其中包括N-取代的3-羟基-5-芳基氨基异噻唑-4-羧酰胺类化合物。还包括互变异噻唑-3（2H）-酮。
• US7429667B2
  申请人：——

  公开号：US7429667B2

  公开（公告）日：2008-09-30
• US7652047B2
  申请人：——

  公开号：US7652047B2

  公开（公告）日：2010-01-26
• [EN] PHENYLAMINO ISOTHIAZOLE CARBOXAMIDINES AS MEK INHIBITORS<br/>[FR] PHENYLAMINO ISOTHIAZOLE CARBOXAMIDINES COMME INHIBITEURS DE MEK
  申请人：VALEANT PHARMACEUTICALS INT

  公开号：WO2006133417A1

  公开（公告）日：2006-12-14

  [EN] The invention concerns compounds of formula (I) which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted- 3-hydroxy-5- arylamino-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)- ones.
  [FR] L'invention concerne des composés de formule (I) qui inhibent la MEK et qui ont une activité comme agents anti-néoplasiques. Ces composés comprennent des 3-hydroxy-5- arylamino-isothiazole-4-carboxamidines N-substituées. Ils comprennent aussi les tautomères des isothiazol-3(2H)- ones.