methyl 4-benzoate | 89667-16-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-benzoate
• 英文别名: methyl 4-[Hydroxy(pyridin-3-yl)methyl]benzoate；Methyl 4-[Hydroxy(3-pyridyl)methyl]benzoate；Benzoic acid, 4-(hydroxy-3-pyridinylmethyl)-, methyl ester
• CAS: 89667-16-3
• 化学式: C₁₄H₁₃NO₃
• 分子量: 243.262
• InChiKey: TUYCYGNNTNWZFQ-UHFFFAOYSA-N

物化性质

• 熔点：
  150-152 °C
• 沸点：
  431.8±35.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-benzoate 在 N-甲基吗啉 、 manganese(IV) oxide 、 nickel(IV) oxide 、 sodium hydroxide 、 4 A molecular sieve 、 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 、 四氯化碳 、 N,N-二甲基甲酰胺 、 乙腈 、 苯 为溶剂， 反应 47.5h， 生成 (-)-(E,Z)-7-<4-<4-<<<2-(trans)-phenylcyclopropyl>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：

  3-pyridyllithium 、 对甲酰基苯甲酸甲酯 以 乙醚 为溶剂， 生成 methyl 4-benzoate
  参考文献：
  名称：

  苯基3-吡啶基酮的Wittig反应中的立体选择性：酰胺取代基对优先（E）-烯烃形成的影响

  摘要：

  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。

  DOI：

  10.1016/s0040-4039(98)01194-0

文献信息

• Preparation of substituted alkenoic acids
  申请人：Eli Lilly and Company

  公开号：US05849922A1

  公开（公告）日：1998-12-15

  This invention relates to a highly selective process for preparation of E-.omega.-phenyl-.omega.-(3-pyridyl)-.omega.-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.

  这项发明涉及一种高度选择性的过程，用于制备在苯环上带有氨甲酰基取代的噁唑基或噁唑啉基的E-ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物，该衍生物表现出对血栓素受体拮抗作用和/或血栓素合酶抑制作用的效用，以及用于制备这些衍生物的中间体。
• Carbamoyl substituted oxazoles as thromboxane receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0811621A3

  公开（公告）日：1998-02-04

  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.

  这项发明涉及一种碳酰基取代的杂环化合物，它们是ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物，在苯环上带有碳酰基取代的噁唑基或噁唑烯基，并且表现出对血栓素受体拮抗作用和/或血栓素合酶抑制作用的效用，以及含有它们的药物配方、它们的使用方法，以及用于它们的制备的过程和中间体。
• Carbamoyl substituted heterocycles
  申请人：Eli Lilly and Company

  公开号：US05849766A1

  公开（公告）日：1998-12-15

  This invention relates to carbamoyl substituted heterocycles which are .omega.-phenyl-.omega.-(3-pyridyl)-.omega.-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.

  这项发明涉及一种带有在苯环上带有羰胺基取代的氧唑基或氧唑烯基的.omega.-苯基-.omega.-(3-吡啶基)-.omega.-烯酸衍生物的杂环化合物，其具有对血栓素受体拮抗作用和/或血栓素合酶抑制作用的效用，以及含有它们的药物配方、它们的使用方法，以及用于它们的制备的过程和中间体。
• 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。
• Carbamoly substituted heterocycles
  申请人：Eli Lilly and Company

  公开号：US06114534A1

  公开（公告）日：2000-09-05

  This invention relates to carbamoyl substituted heterocycles which are .omega.-phenyl-.omega.-(3-pyridyl)-.omega.-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取代的杂环，其为ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物，在苯环上带有氨基甲酰取代的噁唑基或噁唑啉基，并且展示了用于抗血栓素受体拮抗和/或抗血栓素合成酶抑制的效用，以及含有它们的制药配方、它们的使用方法以及它们的制备过程和中间体。