2-(N-苄基-N-甲基氨基)乙基甲基 2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯 | 59875-58-0

• 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
• 中文名称: 2-(N-苄基-N-甲基氨基)乙基甲基 2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯
• 中文别名: 2-[苯甲基(甲基)氨基]乙基甲基2,6-二甲基-4-(3-硝基苯基)吡啶-3,5-二羧酸酯；2-(N-苄基-N-甲基氨基)乙基甲基2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯；脱氢尼卡地平
• 英文名称: 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)pyridine-3,5-dicarboxylate
• 英文别名: 2,6-Dimethyl-4-(3-nitrophenyl) pyridine-3, 5-dicarboxylic acid 3-methyl ester 5-(N-methylbenzylamino)ethyl ester；Nicardipine pyridine metabolite II；3-O-[2-[benzyl(methyl)amino]ethyl] 5-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate
• CAS: 59875-58-0
• 化学式: C₂₆H₂₇N₃O₆
• 分子量: 477.517
• InChiKey: GROZWIBBDLLXKU-UHFFFAOYSA-N

物化性质

• 熔点：
  154-156°C

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  8

ADMET

代谢

去氢尼卡地平是尼卡地平的一个已知人体代谢物。

Dehydronicardipine is a known human metabolite of Nicardipine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  2-(N-苄基-N-甲基氨基)乙基甲基 2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 methyl 2-(N-methylamino)ethyl 4-(m-aminophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Synthesis of the metabolites of 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride (nicardipine hydrochloride, YC-93).

  摘要：

  合成了 2-(N-苄基-N-甲基氨基)乙基甲基 2，6-二甲基-4-(间硝基苯基)-1，4-二氢吡啶-3，5-二甲酸酯盐酸盐（YC-93）的八种代谢物（M-1-M-6、M-8、M-9），并通过与合成化合物的对比确定了代谢物的结构。

  DOI：

  10.1248/cpb.28.2609
• 作为产物：
  描述：

  尼卡地平 在 硝酸 作用下， 生成 2-(N-苄基-N-甲基氨基)乙基甲基 2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯
  参考文献：
  名称：

  Synthesis of the metabolites of 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride (nicardipine hydrochloride, YC-93).

  摘要：

  合成了 2-(N-苄基-N-甲基氨基)乙基甲基 2，6-二甲基-4-(间硝基苯基)-1，4-二氢吡啶-3，5-二甲酸酯盐酸盐（YC-93）的八种代谢物（M-1-M-6、M-8、M-9），并通过与合成化合物的对比确定了代谢物的结构。

  DOI：

  10.1248/cpb.28.2609

文献信息

• Intramolecular Electron Transfer in the Photochemistry of Some Nitrophenyldihydropyridines
  作者：Elisa Fasani、Maurizio Fagnoni、Daniele Dondi、Angelo Albini

  DOI：10.1021/jo052463z

  日期：2006.3.1

  The lowest singlet is localized on the dihydropyridine moiety (1PyH2-Ph) and emits a blue fluorescence (with close to unitary efficiency in glass at 77 K). In 3-nitrophenyl derivatives (PyH2-PhNO2, some of which are photolabile drugs) the fluorescence is completely quenched. Reasonably, this is due to intramolecular electron transfer between the close-lying donor and acceptor moieties to give the charge-separated

  4-苯基-1,4-二氢吡啶-3,5-二羧酸酯包含两个被sp 3碳隔开的π发色团。最低的单峰位于二氢吡啶部分（1 PyH 2 -Ph）上，并发出蓝色荧光（在77 K的玻璃中具有接近统一的效率）。在3-硝基苯基衍生物（PyH 2 -PhNO 2，其中一些是对光不稳定的药物）中，荧光被完全淬灭。合理地，这是由于在紧密的供体和受体部分之间进行分子内电子转移，从而产生了电荷分离的物质（PyH 2 • + -PhNO 2 • -）。在77 K的EPA玻璃中，背电子转移产生二氢吡啶定位的三重态（3 PyH 2 -PhNO 2），发出黄色磷光。在溶液中，从上二氢吡啶部分发起rearomatization，最后得到PY-PHNO的自由基阳离子脱质子化2具有低量子产率（5×10 - 4〜5×10 - 3，通过在254 nm处照射而增加至0.013，其中硝基苯基发色团的直接激发起作用）。在三乙胺的存在下，反应变
• Processes of manufacturing substituted-1,4-dihydropyridines, improved aqueous solutions thereof, and processes of manufacturing the solutions
  申请人：Jobdevairakkam Christopher N.

  公开号：US20080125595A1

  公开（公告）日：2008-05-29

  A process of preparing a stable parenteral solution of a 1,4-dihydropyridine salt, such as nicardipine hydrochloride, in an acidic aqueous medium. The presence of L-arginine in the solution enhances the solubility of the salt, which is poorly soluble in water. An aqueous, injectable isotonic solution at pH about 3.5-3.6 consists essentially of nicardipine hydrochloride, L-arginine, and a sugar alcohol. An improved single pot manufacturing process for obtaining unsymmetrical 1,4-dihydropyridines by using more than one mole equivalent of aldehyde with respect to the other reactants (amino crotonate and acetoacetate ester). The reaction can be conducted in a solvent present at 20 times the amount of any one component. A process for changing one polymorph of nicardipine hydrochloride (Form A) into another (Form B), and a separate process for the reverse (Form B into Form A).

  一种制备1,4-二氢吡啶盐（如盐酸尼卡地平）的稳定无菌溶液的工艺，该工艺在酸性水介质中进行。溶液中存在L-精氨酸，可增强盐的溶解度，而盐在水中溶解度较差。该无菌溶液为水溶性、注射用的等渗溶液，pH值约为3.5-3.6，主要由盐酸尼卡地平、L-精氨酸和糖醇组成。 一种改进的单锅制造工艺，用于通过使用超过其他反应物（氨基丙烯酸酯和乙酰乙酸酯）的摩尔当量的醛类来获得非对称的1,4-二氢吡啶。该反应可以在溶剂中进行，溶剂的量为任何一个组分的20倍。 一种将尼卡地平盐酸的一种多晶形式（A型）转变为另一种多晶形式（B型）的工艺，以及将B型转变为A型的单独工艺。
• 一种吡啶地平的制备方法
  申请人：重庆常捷医药有限公司

  公开号：CN117551027A

  公开（公告）日：2024-02-13

  将地平类药物加入到有机溶剂中，加入活性炭，通入氧气回流反应，以简易和低成本方式制备得到吡啶地平。
• Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4
  作者：F. Peter Guengerich、William R. Brian、Masahiko Iwasaki、Marie Agnes Sari、Catharina Baeaernhielm、Peder Berntsson

  DOI：10.1021/jm00110a012

  日期：1991.6

  A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was approximately 10(3) times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-4.50 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.
• Structural effects on the reactivity 1,4-dihydropyridines with alkylperoxyl radicals and ABTS radical cation
  作者：C Yáñez、C López-Alarcón、C Camargo、V Valenzuela、J.A Squella、L.J Núñez-Vergara

  DOI：10.1016/j.bmc.2004.01.050

  日期：2004.5

  A series of eight commercial C-4 substituted 1,4-dihydropyridines and other synthesized related compounds were tested for direct potential scavenger effect towards alkylperoxyl radicals and ABTS radical cation in aqueous Britton-Robinson buffer pH 7.4. A direct quenching radical species was established. The tested 1,4-dihydropyridines were 8.3-fold more reactive towards alkylperoxyl radicals than ABTS cation radical, expressed by their corresponding kinetic rate constants. Furthermore, NPD a photolyte of nifedipine and the C-4 unsubstituted 1,4-DHP were the most reactive derivatives towards alkylperoxyl radicals. The pyridine derivative was confirmed by GOMS technique as the final product of reaction. In consequence, the reduction of alkylperoxyl and ABTS radicals by 1,4-dihydropyridines involved an electron transfer process. Also, the participation of the hydrogen of the 1-position appears as relevant on the reactivity. Results of reactivity were compared with Trolox. (C) 2004 Elsevier Ltd. All rights reserved.