N-<4-(cyclohexyloxy)butyl>-2-<4-(3-pyridylcarbonyl)phenyl>-4-oxazolecarboxamide | 200400-57-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-<4-(cyclohexyloxy)butyl>-2-<4-(3-pyridylcarbonyl)phenyl>-4-oxazolecarboxamide
• 英文别名: N-(4-cyclohexyloxybutyl)-2-[4-(pyridine-3-carbonyl)phenyl]-1,3-oxazole-4-carboxamide
• CAS: 200400-57-3
• 化学式: C₂₆H₂₉N₃O₄
• 分子量: 447.534
• InChiKey: PGYQZMNFQYYZHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  94.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5-羧基戊基)三苯基溴化磷 、 N-<4-(cyclohexyloxy)butyl>-2-<4-(3-pyridylcarbonyl)phenyl>-4-oxazolecarboxamide 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (E,Z)-7-<4-<4-<<<4-(cyclohexyloxy)butyl>amino>carbonyl>-2-oxazolyl>phenyl>-7-(3-pyridyl)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
• 作为产物：
  描述：

  methyl 4-benzoate 在 N-甲基吗啉 、 manganese(IV) oxide 、 nickel(IV) oxide 、 sodium hydroxide 、 4 A molecular sieve 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 、 乙腈 、 苯 为溶剂， 反应 45.5h， 生成 N-<4-(cyclohexyloxy)butyl>-2-<4-(3-pyridylcarbonyl)phenyl>-4-oxazolecarboxamide
  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

• Preparation of substituted alkenoic acids
  申请人：ELI LILLY AND COMPANY

  公开号：EP0816361A2

  公开（公告）日：1998-01-07

  This invention relates to a highly selective process for preparation of E-ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as to intermediates therefor.

  本发明涉及一种制备 E-ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物的高选择性工艺，该衍生物在苯基环上带有氨基甲酰基取代的噁唑基或噁唑啉基，可用于血栓素受体拮抗和/或血栓素合成酶抑制，本发明还涉及其中间体。
• US5990308A
  申请人：——

  公开号：US5990308A

  公开（公告）日：1999-11-23
• US6031095A
  申请人：——

  公开号：US6031095A

  公开（公告）日：2000-02-29
• US6075147A
  申请人：——

  公开号：US6075147A

  公开（公告）日：2000-06-13
• US6114534A
  申请人：——

  公开号：US6114534A

  公开（公告）日：2000-09-05