(E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(pyridin-3-yl)hept-6-enoic acid

• 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-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(pyridin-3-yl)hept-6-enoic acid
• 英文别名: (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid；(E)-7-{4-[4-(4-Cyclohexyl-butylcarbamoyl)-oxazol-2-yl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid；(E)-7-[4-[4-(4-cyclohexylbutylcarbamoyl)-1,3-oxazol-2-yl]phenyl]-7-pyridin-3-ylhept-6-enoic acid
• 化学式: C₃₂H₃₉N₃O₄
• 分子量: 529.679
• InChiKey: ZNRZNAHHOIANAO-CCVNUDIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(pyridin-3-yl)hept-6-enoic acid 、 2-二吡啶基酮 、 (5-羧基戊基)三苯基溴化磷 、 potassium tert-butylate 在 AcOH- 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 、 反-2-庚烯酸
  参考文献：
  名称：

  Intermediates in the preparation of substituted alkenoic acids

  摘要：

  本发明涉及一种高选择性的制备E-ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物的方法，其中苯环上带有氨基甲酰基取代的噁唑基或噁唑烷基，该衍生物表现出用于血栓素受体拮抗和/或血栓素合酶抑制的效用，以及其中间体。

  公开号：

  US05990308A1
• 作为产物：
  描述：

  对苯二甲醇 在 N-甲基吗啉 、 咪唑 、 四氯化碳 、 manganese(IV) oxide 、 nickel(IV) oxide 、 sodium hydroxide 、 jones reagent 、 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 、 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 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 苯 为溶剂， 生成 (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]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. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives

  摘要：

  Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00353-9

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。
• Carbamoyl substituted oxazoles as thromboxane receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0811621A2

  公开（公告）日：1997-12-10

  This invention relates to carbamoyl substituted heterocycles which are ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring and which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as pharmaceutical formulations containing them, methods for their use, and processes and intermediates for their preparation.

  本发明涉及氨基甲酰基取代的杂环，这些杂环是ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物，在苯基环上带有氨基甲酰基取代的噁唑基或噁唑啉基，具有血栓素受体拮抗和/或血栓素合成酶抑制作用，还涉及含有这些杂环的药物制剂、使用方法以及制备这些杂环的工艺和中间体。
• 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。
• 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.
• US5990308A
  申请人：——

  公开号：US5990308A

  公开（公告）日：1999-11-23