(E)-7-{4-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-oxazol-2-yl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid | 212309-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-7-{4-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-oxazol-2-yl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid
• 英文别名: (E)-7-[4-[4-[(4-chlorophenyl)sulfonylcarbamoyl]-1,3-oxazol-2-yl]phenyl]-7-pyridin-3-ylhept-6-enoic acid
• CAS: 212309-47-2
• 化学式: C₂₈H₂₄ClN₃O₆S
• 分子量: 566.034
• InChiKey: VAHRCTHWRYPGTD-GFXGDVFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (E)-7-{4-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-oxazol-2-yl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid 以 四氢呋喃 、 乙醚 为溶剂， 生成 2-[4-((E)-6-Methoxycarbonyl-1-pyridin-3-yl-hex-1-enyl)-phenyl]-oxazole-4-carboxylic acid methyl ester 、 (E)-7-{4-[4-(4-Chloro-benzenesulfonyl)-methyl-aminocarbonyl]-oxazol-2-yl}-phenyl)-7-pyridin-3-yl-hept-6-enoic acid methyl ester
  参考文献：
  名称：

  Development of Dual-Acting Agents for Thromboxane Receptor Antagonism and Thromboxane Synthase Inhibition. 3. Synthesis and Biological Activities of Oxazolecarboxamide-Substituted ω-Phenyl-ω-(3-pyridyl)alkenoic Acid Derivatives and Related Compounds

  摘要：

  A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA(2) receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid (14) with K-d = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI(2) level, and absence of agonist activity.

  DOI：

  10.1021/jm980173n
• 作为产物：
  描述：

  methyl 4-benzoate 在 N-甲基吗啉 、 manganese(IV) oxide 、 nickel(IV) oxide 、 sodium hydroxide 、 potassium phosphate 、 三氟甲磺酸酐 、 二苯基亚砜 、 potassium tert-butylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 68.0h， 生成 (E)-7-{4-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-oxazol-2-yl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid
  参考文献：
  名称：

  Development of Dual-Acting Agents for Thromboxane Receptor Antagonism and Thromboxane Synthase Inhibition. 3. Synthesis and Biological Activities of Oxazolecarboxamide-Substituted ω-Phenyl-ω-(3-pyridyl)alkenoic Acid Derivatives and Related Compounds

  摘要：

  A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA(2) receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid (14) with K-d = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI(2) level, and absence of agonist activity.

  DOI：

  10.1021/jm980173n

文献信息

• Stereoselectivity in the Wittig reaction of phenyl 3-pyridyl ketones: Amide substituent effect on the preferential (E)-ollefin formation
  作者：Kumiko Takeuchi、Todd J. Kohn

  DOI：10.1016/s0040-4039(98)01194-0

  日期：1998.8

  A Wittig reaction of amide substituted phenyl 3-pyridyl ketones with “nonstabilized” phosphorus ylides which contain a carboxyl terminus preferentially forms (E)-olefin. The preference for this stereoselectivity stems from either hydrogen bonding or salt-bridge formation between the amide group and the carboxyl terminus during the oxaphosphetane intermediate formation.

  酰胺取代的苯基3-吡啶基酮与含有羧基末端的“不稳定的”磷酰化物的维蒂希反应优选形成（E）-烯烃。对于这种立体选择性的偏爱是由于在氧杂膦烷中间体的形成过程中，酰胺基团与羧基末端之间的氢键键合或盐桥形成。
• Development of Dual-Acting Agents for Thromboxane Receptor Antagonism and Thromboxane Synthase Inhibition. 3. Synthesis and Biological Activities of Oxazolecarboxamide-Substituted ω-Phenyl-ω-(3-pyridyl)alkenoic Acid Derivatives and Related Compounds
  作者：Kumiko Takeuchi、Todd J. Kohn、Timothy A. True、Dale E. Mais、James H. Wikel、Barbara G. Utterback、Virginia L. Wyss、Joseph A. Jakubowski

  DOI：10.1021/jm980173n

  日期：1998.12.1

  A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA(2) receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid (14) with K-d = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI(2) level, and absence of agonist activity.