4-phenylpyridine-3-carboxylic acid methyl ester | 70647-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-phenylpyridine-3-carboxylic acid methyl ester
• 英文别名: methyl 4-phenylnicotinate；Methyl 4-phenylpyridine-3-carboxylate
• CAS: 70647-05-1
• 化学式: C₁₃H₁₁NO₂
• 分子量: 213.236
• InChiKey: VOXLHHIYDOQDQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-phenylpyridine-3-carboxylic acid methyl ester 在 盐酸 、 sodium hydroxide 、 PPA 、 zinc(II) iodide 、 肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-aza-9-hydroxy-9-fluorene carboxylic acid hydrazide
  参考文献：
  名称：

  9-Hydroxyazafluorenes and Their Use in Thrombin Inhibitors

  摘要：

  Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (K(i) = 0.49 nM for human thrombin, 2x APTT = 0.37 microM in human plasma) and pharmacokinetic properties (F = 39%, iv T(1/2) = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (19b), with high potency (K(i) = 0.40 nM, 2x APTT = 0.18 microM), excellent pharmacokinetic properties (F = 55%, T(1/2) = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl(3)-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 microg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.

  DOI：

  10.1021/jm049423s
• 作为产物：
  描述：

  烟酸甲酯 在 邻四氯苯醌 、 lithium chloride 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 4-phenylpyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Syntheses of 2-Azafluorenones from 3-Substituted 4-Arylpyridines

  摘要：

  3-Substituted 4-arylpyridines (5a-i) were synthesized in good yields by reaction of mixed copper, zinc aryl organometallics (2a-e) with 1-ethoxycarbonyl-pyridinium chlorides (1a-d) followed by o-chloranil oxidation under reflux in toluene. The 4-arylpyridines (5a-i) are obtained predominantly. Having compounds (5a-i) in hand, a convenient method was developed for the synthesis of 2-azafluorenones (7a-f) by using cyclization of 4-arylpyridines (5a-i) with polyphosphoric acid.

  DOI：

  10.3987/com-92-6199

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020119992A1

  公开（公告）日：2002-08-29

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 or a pharmaceutically acceptable salt thereof, e.g. where R 3 is —CH 2 NH 2 , —CH 2 CH 2 NH 2 , or —CH 2 NHC(O)OC(CH 3 ) 3 .

  该发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构： 1 或其药用可接受的盐，例如其中R 3 为—CH 2 NH 2 ，—CH 2 CH 2 NH 2 ，或—CH 2 NHC(O)OC(CH 3 ) 3 。
• Substrate Control in the Gold(I)-Catalyzed Cyclization of β<i>-</i>Propargylamino Acrylic Esters and Further Transformations of the Resultant Dihydropyridines
  作者：Jiří Mikušek、Petr Matouš、Eliška Matoušová、Martin Janoušek、Jiří Kuneš、Milan Pour

  DOI：10.1002/adsc.201600412

  日期：2016.9.15

  β‐propargylamino acrylic esters with a push‐pull olefinic bond afforded good to high yields of dihydropyridines upon treatment with 5% tris(2‐furyl)phosphine‐gold(I) chloride/silver(I) tetrafluoroborate [(TFP)AuCl/AgBF4] in anhydrous benzene. Carbamate and sulfonyl groups were employed for nitrogen protection. On a model enyne, the p‐methoxybenzenesulfonyl (MBS) group was found to be a better protective

  N-保护的带有推挽式烯烃键的β-炔丙基氨基丙烯酸酯，在用5％的三（2-呋喃基）膦-氯化金（I）/四氟硼酸银（I）处理后，可提供高至高产率的二氢吡啶。在无水苯中的AuCl / AgBF 4 ]。氨基甲酸酯和磺酰基用于氮保护。在模型恩尼（Enyne）上，p就环化收率以及消除相应2,3,4-三取代吡啶的收率而言，发现甲氧基苯磺酰基（MBS）基比甲苯磺酰基更好。Boc保护的二氢吡啶在环化条件下进行了部分脱保护/氧化，这使得相应吡啶的更直接，一锅法制备成为可能。在另一个应用中，将被保护为稳定的甲氧基氨基甲酸酯的适当取代的衍生物进行催化氢化，得到已知的帕罗西汀前体。烯炔环化的化学选择性（二氢吡啶与。吡咯）除其他因素外，还受C-3取代的支配。当C-3未取代时，无论催化剂/条件如何，均以二氢吡啶为唯一产物。
• Synthesis of Azafluorenones using Zeolites.
  作者：R. Sreekumar、P. Rugmini、R. Padmakumar

  DOI：10.1080/00397919808007183

  日期：1998.6

  Abstract A convenient method for the synthesis of various azafluorenones (2a-f & 4a-d) by cyclization of substituted arylpyridines (1a-f & 3a-d) using zeolites are described.

  摘要描述了使用沸石环化取代的芳基吡啶 (1a-f & 3a-d) 合成各种氮杂芴酮 (2a-f & 4a-d) 的简便方法。
• [EN] BENZYLAMINE DERIVATIVES AND THEIR USE AS THROMBIN INHIBITORS<br/>[FR] DERIVES DE BENZYLAMINE ET LEUR UTILISATION COMME INHIBITEURS DE THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002050056A1

  公开（公告）日：2002-06-27

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. where R3 is -CH2NH2, -CH2CH2NH2, or -CH2NHC(O)OC(CH3)3.

  本发明的化合物具有以下结构，或其药学上可接受的盐，例如其中R3为-CH2NH2，-CH2CH2NH2或-CH2NHC（O）OC（CH3）3，对于抑制凝血酶和相关的血栓闭塞非常有用。
• Phamacologically active 5-carboxy-2-(5-tetrazolyl) pyridines
  申请人：Zyma SA

  公开号：US04904675A1

  公开（公告）日：1990-02-27

  Compounds of the formula I ##STR1## wherein the groups A, R.sub.1, R.sub.2 and R.sub.3 are as defined in the specification, exhibit valuable pharmacological properties, especially as antifibrotic agents. They are prepared by methods known per se.

  式I的化合物##STR1##其中A、R.sub.1、R.sub.2和R.sub.3的基团如规范中所定义，表现出有价值的药理学特性，特别是作为抗纤维化剂。它们通过已知的方法制备。