4(Z)-6-cis-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>hexenoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4(Z)-6-cis-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>hexenoic acid
• 英文别名: (Z)-6-((4S,5R)-2,2-Dimethyl-4-pyridin-3-yl-[1,3]dioxan-5-yl)-hex-4-enoic acid；(Z)-6-[(4S,5R)-2,2-dimethyl-4-pyridin-3-yl-1,3-dioxan-5-yl]hex-4-enoic acid
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: CTOWXSBMFAJYEK-RAQZUPNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-甲基-2-(苯基巯基)丙醛 、 4(Z)-6-cis-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>hexenoic acid 在 对甲苯磺酸 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以63%的产率得到(Z)-6-[(2R,4R,5S)-2-(2-phenylsulfanylpropan-2-yl)-4-pyridin-3-yl-1,3-dioxan-5-yl]hex-4-enoic acid
  参考文献：
  名称：

  Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of [2-Substituted-4-(3-pyridyl)-1,3-dioxan-5-yl]alkenoic Acids

  摘要：

  The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.

  DOI：

  10.1021/jm00004a014
• 作为产物：
  描述：

  (3-丙羧基)三苯基溴化膦 、 (4S,5R)-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>acetaldehyde 在 potassium tert-butylate 作用下， 生成 4(Z)-6-cis-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>hexenoic acid
  参考文献：
  名称：

  Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of [2-Substituted-4-(3-pyridyl)-1,3-dioxan-5-yl]alkenoic Acids

  摘要：

  The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.

  DOI：

  10.1021/jm00004a014

文献信息

• 4-pyridyl substituted-1,3-dioxane compounds
  申请人：Imperial Chemical Industries PLC

  公开号：US05166213A1

  公开（公告）日：1992-11-24

  The invention concerns novel, pharmaceutically useful 1,3-dioxane alkenoic acid derivatives of the formula I containing a pyridyl moiety at position 4 of the dioxane ring and in which the groups at positions 2, 4 and 5 have cis-relative stereochemistry, X is hydrogen, alkoxy or hydroxy, Y is vinylene, n is 1 or 2, A.sup.1 is alkylene, R.sup.1 is a variety of substituents defined hereinafter, and R.sup.2 is hydroxy, a physiologically acceptable alcohol residue or alkanesulphonamido, and the pharmaceutically acceptable salts thereof. The invention also includes processes for the manufacture and use of the acid derivatives as well as pharmaceutical compositions for therapeutic use in one or more of a variety of diseases such as ischaemic heart disease, cerebrovascular disease, asthmatic disease and/or inflammatory disease.

  这项发明涉及一种新颖的、具有药用价值的1,3-二氧杂环戊烯酸衍生物，其化学式为I，其中在二氧杂环丁烷环的4位含有吡啶基团，且在2、4和5位的基团具有顺式立体化学构型，X为氢、烷氧基或羟基，Y为乙烯基，n为1或2，A.sup.1为烷基，R.sup.1为下文定义的各种取代基，R.sup.2为羟基、生理学上可接受的醇残基或烷磺酰胺基，以及其药用盐。该发明还包括制造和使用这些酸衍生物的方法，以及用于治疗各种疾病的药物组合物，如缺血性心脏病、脑血管疾病、哮喘疾病和/或炎症性疾病。
• US5053415A
  申请人：——

  公开号：US5053415A

  公开（公告）日：1991-10-01
• US5166213A
  申请人：——

  公开号：US5166213A

  公开（公告）日：1992-11-24
• US5248780A
  申请人：——

  公开号：US5248780A

  公开（公告）日：1993-09-28
• US5401849A
  申请人：——

  公开号：US5401849A

  公开（公告）日：1995-03-28