CL 184005 | 140466-18-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: CL 184005
• 英文别名: 3-<<3-<phosphinyl>oxy>phenyl>methyl>-5-methylthiazolium hydroxide inner salt；(2-Methoxycarbonyl-3-tetradecoxyphenyl) [3-[(5-methyl-1,3-thiazol-3-ium-3-yl)methyl]phenyl] phosphate
• CAS: 140466-18-8
• 化学式: C₃₃H₄₆NO₇PS
• 分子量: 631.771
• InChiKey: VGVUQNMRGKNUJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  43
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二羟基苯甲酸 在 硫酸 、 sodium acetate 、 sodium hydride 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 197.5h， 生成 CL 184005
  参考文献：
  名称：

  Analogs of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor

  摘要：

  A series of aryl phosphoglyceride (3, 19-6 1) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) were prepared. A group of four bifunctional phosphorus reagents (5a-c and 7) were developed that allowed the preparation of these aryl phosphates in which the position of aromatic substitution can be varied. These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets. Selected compounds were also evaluated for their ability to displace [H-3]PAF from its receptor on rabbit platelets. These in vitro data were compared to similar data obtained for a number of known PAF antagonists. The compounds were evaluated in vivo, in both the mouse and rabbit, for their ability to prevent death induced by a lethal challenge of PAF. The relationships between the biological activity and the nature, lipophilicity, and position of substituents of the aromatic rings were studied. Compound 105 (CL 184005) has been selected to undergo further development as a potential therapeutic agent for the treatment of septic shock in man.

  DOI：

  10.1021/jm00087a023

文献信息

• Bis-arylphosphate ester antagonists of platelet activating factor
  申请人：American Cyanamid Company

  公开号：US05147864A1

  公开（公告）日：1992-09-15

  The invention is novel compounds of the formula: ##STR1## wherein: X is a phenyl or naphthyl ring optionally substituted in any position with one to four substituents of; (i) --R.sub.2, wherein R.sub.2 is C.sub.1 -C.sub.25 alkyl, C.sub.1 -C.sub.25 alkenyl, C.sub.1 -C.sub.25 alkoxy, C.sub.1 -C.sub.25 thioalkyl, C.sub.1 -C.sub.25 alkenyloxy, phenyl, phenoxy, substituted phenyl or substituted phenoxy wherein the substituents are C.sub.1 -C.sub.20 alkyl, C.sub.1 -C.sub.20 alkoxy, halogen and trifluoremethyl; (ii) hydrogen, halogen, trifluoromethyl, cyano and nitro; (iii) --CO.sub.2 R.sub.3, --CONHR.sub.3, --CHO, OCONHR.sub.3, and --NHCOR.sub.3 wherein R.sub.3 is C.sub.1 -C.sub.25 alkyl, C.sub.1 -C.sub.25 alkenyl, phenyl or substituted phenyl wherein the substituents are C.sub.1 -C.sub.20 alkyl, C.sub.1 -C.sub.20 alkoxy, halogen or trifluoromethyl; R.sub.1 is one to four substituents on the aromatic ring which may be in any position and are hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy or halogen; --CH.sub.2 --Y is a single substituent of the aromatic ring which may occupy any position where Y is ##STR2## wherein R.sub.4 represents one to four substituents of the heterocyclic ring which may occupy a non-hetero atom position and is C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy, hydrogen or halogen; and n is the integer 0 or 1 which are antagonists of platelet activating factor.

  该发明是一种新型化合物，其化学式为：##STR1## 其中：X是苯环或萘环，可在任何位置上用1到4个取代基替换，包括：（i）-R2，其中R2是C1-C25烷基，C1-C25烯基，C1-C25烷氧基，C1-C25硫代烷基，C1-C25烯氧基，苯基，苯氧基，取代苯基或取代苯氧基，其中取代基是C1-C20烷基，C1-C20烷氧基，卤素和三氟甲基；（ii）氢，卤素，三氟甲基，氰基和硝基；（iii）-CO2R3，-CONHR3，-CHO，OCONHR3和-NHCOR3，其中R3是C1-C25烷基，C1-C25烯基，苯基或取代苯基，其中取代基是C1-C20烷基，C1-C20烷氧基，卤素或三氟甲基；R1是芳香环上的1到4个取代基，可以在任何位置上，包括氢，C1-C5烷基，C1-C5烷氧基或卤素；-CH2-Y是芳香环的单个取代基，可以占据任何位置，其中Y是##STR2## 其中R4代表杂环环上的1到4个取代基，可以占据非杂原子位置，是C1-C5烷基，C1-C5烷氧基，氢或卤素；n是整数0或1，是血小板活化因子的拮抗剂。
• Analogs of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor
  作者：A. Wissner、M. L. Carroll、K. E. Green、S. S. Kerwar、W. C. Pickett、R. E. Schaub、L. W. Torley、S. Wrenn、C. A. Kohler

  DOI：10.1021/jm00087a023

  日期：1992.5

  A series of aryl phosphoglyceride (3, 19-6 1) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) were prepared. A group of four bifunctional phosphorus reagents (5a-c and 7) were developed that allowed the preparation of these aryl phosphates in which the position of aromatic substitution can be varied. These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets. Selected compounds were also evaluated for their ability to displace [H-3]PAF from its receptor on rabbit platelets. These in vitro data were compared to similar data obtained for a number of known PAF antagonists. The compounds were evaluated in vivo, in both the mouse and rabbit, for their ability to prevent death induced by a lethal challenge of PAF. The relationships between the biological activity and the nature, lipophilicity, and position of substituents of the aromatic rings were studied. Compound 105 (CL 184005) has been selected to undergo further development as a potential therapeutic agent for the treatment of septic shock in man.