dimethyl 1,2,6-trimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate | 70008-26-3

• 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: dimethyl 1,2,6-trimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: dimethyl 1,4-dihydro-1,2,6-trimethyl-4-phenylpyridine-3,5-dicarboxylate；1,2,6-trimethyl-4-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester；3,5-Dimethyl 1,2,6-trimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate；dimethyl 1,2,6-trimethyl-4-phenyl-4H-pyridine-3,5-dicarboxylate
• CAS: 70008-26-3
• 化学式: C₁₈H₂₁NO₄
• mdl: MFCD01874521
• 分子量: 315.369
• InChiKey: UASXCCOIZXMTDS-UHFFFAOYSA-N

物化性质

• 熔点：
  151-153 °C
• 沸点：
  420.4±45.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl 1,2,6-trimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate 在 potassium phosphate 、 乙二胺四乙酸 、 Emulgen 911 、 human liver cytochrome b₅ 、 human liver HL 39 lipid extract 、 rabbit liver NADPH-P-450 reductase 、 yeast P-450 IIIA₄ 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 dimethyl 4-phenyl-2,6-dimethyl-3,5-pyridinedicarboxylate
  参考文献：
  名称：

  Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4

  摘要：

  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.

  DOI：

  10.1021/jm00110a012
• 作为产物：
  描述：

  苯甲醛 在 ammonium acetate 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 6.17h， 生成 dimethyl 1,2,6-trimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  在不添加氧化剂的情况下，由N-取代的二氢吡啶与BF 3 OEt 2合成吡啶鎓盐

  摘要：

  在不需要通常添加的氧化剂如醌，硝酸盐，过氧化物和铬酸盐的情况下进行的反应中，用BF 3 OEt 2作为芳构化促进剂将N-取代的二氢吡啶转化为吡啶鎓盐。它采用一种具有优化研究ñ -苯基汉奇二氢吡啶酯（1A），以获得相应的Ñ含-phenylpyridinium铵季盐（2A）中的溶液进行，以限定用于芳构化反应的最佳条件：3当量的BF 3 OET 2在0 °C，在黑暗中，在大气中CH 2 Cl 2中使产率高达80％。这些条件也可以应用于N-取代的二氢吡啶和1，4-二氢吡啶的另外的实例。

  DOI：

  10.1016/j.tetlet.2015.02.119

文献信息

• Gold-Catalyzed Multicomponent Reaction: Facile Strategy for the Synthesis of<i>N</i>-Substituted 1,4-Dihydropyridines by Using Activated Alkynes, Aldehydes, and Methanamine
  作者：Shaohua Wang、Huoji Chen、Hong Zhao、Hua Cao、Yongjian Li、Qiang Liu

  DOI：10.1002/ejoc.201301203

  日期：2013.11

  A convenient and efficient gold-catalyzed multicomponent reaction was developed for the synthesis of a wide range of N-substituted 1,4-dihydropyridines, which are found in a variety of bioactive compounds. This process proceeds smoothly under mild conditions with the use of commercially available substrates and affords the desired products in good to excellent yields. This method provides a highly

  开发了一种方便有效的金催化多组分反应，用于合成各种 N-取代的 1,4-二氢吡啶，这些化合物存在于各种生物活性化合物中。该过程在温和条件下使用市售底物顺利进行，并以良好到极好的产率提供所需的产品。该方法为从活化炔烃、醛和甲胺制备 N-取代 1,4-二氢吡啶提供了一种高效的合成路线，催化方法稀缺。
• A classical but new kinetic equation for hydride transfer reactions
  作者：Xiao-Qing Zhu、Fei-Huang Deng、Jin-Dong Yang、Xiu-Tao Li、Qiang Chen、Nan-Ping Lei、Fan-Kun Meng、Xiao-Peng Zhao、Su-Hui Han、Er-Jun Hao、Yuan-Yuan Mu

  DOI：10.1039/c3ob40831k

  日期：——

  activation energies of various hydride transfer reactions was developed according to transition state theory using the Morse-type free energy curves of hydride donors to release a hydride anion and hydride acceptors to capture a hydride anion and by which the activation energies of 187 typical hydride self-exchange reactions and more than thirty thousand hydride cross transfer reactions in acetonitrile were

  根据过渡态理论，使用氢化物​​供体的莫尔斯型自由能曲线释放氢化物阴离子和氢化物受体以捕获氢化物阴离子，开发了一种经典但新颖的动力学方程式，用于估算各种氢化物转移反应的活化能。 187个典型的氢化物自交换反应和超过3万个氢化物交叉转移反应的活化能 乙腈被安全地估计在这项工作中。由于动力学方程式的发展仅基于氢化物转移反应物的相关化学键变化，因此该动力学方程式也应适用于质子转移反应，氢原子转移反应以及所有其他涉及断裂和化学反应的化学反应。化学键的形成。这项工作最重要的贡献之一是实现了氢化物转移反应动力学方程和热力学方程的完美统一。
• Mannich reaction of dihydropyridine derivatives I. Reactions with secondary amines.
  作者：JIRO ARITOMI、SHOZO UEDA、HARUKI NISHIMURA

  DOI：10.1248/cpb.28.3163

  日期：——

  Dialkyl 4-aryl-1, 4-dihydro-2, 6-dimethylpyridine-3, 5-dicarboxylates (III) were subjected to the Mannich reaction with excess paraformaldehyde and secondary amine hydrochloride in boiling ethanolic solution. When the compounds III were treated with a 5-to 7-fold molar excess of the aldehyde and amine salt, 2, 6-bis (2-disubstituted aminoethyl)-dihydropyridine derivatives (V) were obtained in good yields. On treatment with a 2- to 3-fold molar excess of the reactants, compounds III were converted to 2-(2-disubstituted aminoethyl)-6-methyldihydropyridine derivatives (IV) and V. When dioxane was used as a solvent with a 6-fold molar excess of the reactants, the tetrakis (dimethylaminomethyl) derivative (VII) was obtained.

  二烷基 4-芳基-1, 4-二氢-2, 6-二甲基吡啶-3, 5-二羧酸酯 (III) 在沸腾的乙醇溶液中与过量的多聚甲醛和二级胺盐酸盐进行曼尼希反应。当化合物 III经5-至7-倍摩尔过量的醛和胺盐处理时，可获得产率良好的 2, 6-双(2-二取代氨基乙基)-二氢吡啶衍生物 (V)。用2-至3-倍摩尔过量的反应物处理时，化合物 III 转化成 2-(2-二取代氨基乙基)-6-甲基二氢吡啶衍生物 (IV) 和 V。当使用二氧六环作为溶剂并采用6-倍摩尔过量的反应物时，得到四(二甲氨基甲基)衍生物 (VII)。
• [EN] 1,4- DIHYDROPYRIDINE DERIVATIVES WITH HSP MODULATING ACTIVITY<br/>[FR] DÉRIVÉS DE 1,4-DIHYDROPYRIDINE AYANT UNE ACTIVITÉ MODULANT HSP
  申请人：LIPIDART KUTATO FEJLESZTO ES TANACSADO KFT

  公开号：WO2013076516A1

  公开（公告）日：2013-05-30

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R1 is optionally substituted C6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R2 and R3 are independently hydrogen or C1-6alkyl group; R4 and R5 are independently hydrogen, C1-6alkyl group optionally substituted with amino, mono-or di(C1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C1-6alkyl group or C1-6 alkoxy group; R6 is C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl or arylC1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  该发明提供了式（I）的1,4-二氢吡啶衍生物，其中R1是可选择取代的C6-24芳基或含有1至3个氮原子或其他杂原子（如氧和硫）的5至6成员杂芳基，以及它们的组合；R2和R3分别是氢或C1-6烷基基团；R4和R5分别是氢、C1-6烷基基团，可选择地取代为氨基、单或双（C1-6烷基）氨基，或通过氮原子连接的5至24成员可选择融合的杂环基团，可选择地包含额外的1至3个N、O、S杂原子，并可选择地取代为C1-6烷基基团或C1-6烷氧基基团；R6是C1-6烷基、C3-7环烷基、C3-7环烷基C1-6烷基或芳基C1-6烷基基团；以及包括对映异构体、二对映异构体、外消旋混合物、对映异构体混合物和它们的组合，以及多型体、药用可接受盐、溶剂合物、酯类和它们的前药，用于治疗或预防由热休克蛋白介导的疾病。
• 1,4- DIHYDROPYRIDINE DERIVATIVES WITH HSP MODULATING ACTIVITY
  申请人：LIPIDART KUTATÓ FEJLESZTÖ ÉS TANÁCSADÓ KFT.

  公开号：US20140315893A1

  公开（公告）日：2014-10-23

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R 1 is optionally substituted C 6-24 aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R 2 and R 3 are independently hydrogen or C 1-6 alkyl group; R 4 and R 5 are independently hydrogen, C 1-6 alkyl group optionally substituted with amino, mono- or di(C 1-6 alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C 1-6 alkyl group or C 1-6 alkoxy group; R 6 is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl or arylC 1-6 alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  本发明提供了式（I）的1,4-二氢吡啶衍生物，其中R1是可选择取代的C6-24芳基或含有1至3个氮原子或其他杂原子（如氧和硫）的5至6成员杂芳基，以及它们的组合；R2和R3分别是氢或C1-6烷基；R4和R5分别是氢，C1-6烷基（可选择取代氨基，单-或双（C1-6烷基）氨基）或带有氮原子的5至24成员可选择融合的杂环，该杂环可选择包含附加的1至3个N、O、S杂原子并可选择取代C1-6烷基或C1-6烷氧基；R6是C1-6烷基，C3-7环烷基，C3-7环烷基C1-6烷基或芳基C1-6烷基；以及立体异构体，包括对映异构体，顺反异构体，混合对映体和它们的组合，以及其药物学上可接受的盐，溶剂化合物，酯和前药，用于治疗或预防由热休克蛋白介导的疾病。