1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸二(2-甲氧基乙基)酯的合成

对1，4－二氢吡啶类钙拮抗剂西尼地平进行了结构修饰。以双乙烯酮和乙二醇单甲醚为原料，经酯化、缩合、氨化和Hantzsch环化等反应合成了1，4－二氢－2，6二甲基－4－（3－硝基苯基）－3，5－吡啶二羟酸二（2－甲氧基乙基）酯，总收率71％。目标产物结构经^1H NMR和MS确证。     

1,4-二氢-2,6-二甲基-3,5-吡啶二甲酸二乙酯的合成

用季铵盐作相转移催化剂,在较温和的条件下使乙酰乙酸乙酯与甲醛和氨缩合,合成了1,4－二氢－2,6－二甲基－3,5－吡啶二甲酸二乙酯（DHP）,研究了多种反应因素对产物的影响,提出了合成DHP的最佳工艺条件,投料摩尔比mol乙酰乙酸乙酯：mol六次甲基四胺＝2：1.5,20％（wt％）乙醇水溶液作溶剂,反应温度55℃,反应时间45min,产品收率达88％。     

Synthesis and calcium channel antagonist activities of new derivatives of dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates

The new analogues of nifedipine, in which 2-nitrophenyl group at position 4 is replaced by phenylisoxazolyl substituent, were synthesized. The symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates were prepared by classical Hantzsch condensation, and the asymmetrical analogues were synthesized using a procedure reported by Dagnino that involved the condensation of alkyl acetoacetate with alkyl 3-aminocrotonate and 5-phenylisoxazole-3-carboxaldehyde. The structure of all compounds was confirmed by IR, ¹H NMR and Mass spectra. In vitro calcium channel antagonist activities were evaluated as calcium channel antagonists using the high K⁺ concentration of guinea-pig ileum longitudinal smooth muscle (GPILSM) assay. These compounds exhibited moderate calcium antagonist activity (IC₅₀ = 10^?7 to 10^{? 5} M range) relative to the reference drug nifedipine (IC₅₀ = 1.10 ± 0.40 × 10^?8 M).     

4-(3-羟基苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸乙酯的合成和晶体结构

标题化合物C19H23NO5由间羟基苯甲醛、碳酸氢铵、乙酰乙酸乙酯在乙醇溶剂中回流制备.结构通过单晶X-射线衍射法测定,其晶体属三斜晶系,空间群Pi,a=7.4550(15),b=8.9780(18),c=14.099(3)(A),α=80.22(3),β=86.72(3),γ=68.62(3)°, V=865.9(3)(A)3, Z=2, Mr=345.38, Dc=1.325g/cm3, F(000)=368. 晶体结构用直接法解出,经全矩阵最小二乘法对原子参数进行修正,最终的偏离因子为R1=0.0633,wR2=0.1709[I＞2σ(I)].在晶体结构中,二氢吡啶环与苯环之间的二面角为90.0(2)°,分子通过氢键形成有隧道的一维超分子结构.     

Sulfonation of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-2-difluoromethoxyphenyl)-1,4-dihydropyridine (phoridone)

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1568–1569, November, 1989.     

Synthesis of diethyl 4-(phenyl-substituted)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates catalyzed by CoCl2/K-10 montmorillonite in water and their antimicrobial activity

Russian Journal of General Chemistry - A simple and efficient method of one pot synthesis of 1,4-dihydropyridine by three components reaction of aromatic aldehydes with 1,3-dicarbonyl compound,...     

2,6-二甲基-4-苯基-1,4-二氢吡啶-3,5-二甲酸乙酯的合成和晶体结构

标题化合物C1 9H2 3NO4由苯甲醛、尿素、乙酰乙酸乙酯在微波辐射下干反应而得。结构通过单晶X 射线衍射法测定 ,其晶体属单斜晶系 ,空间群P2 1 /c ,a =9.745(2 ) ,b =7.388(2 ) ,c =2 4 .354(5) ,β =92 .60 (3)°,V =1 751 .6(6) 3,Z =4,Mr=32 9.38,Dc=1 2 4 9g/cm3,μ(MoKα) =0 .0 87mm- 1 ,F(0 0 0 ) =70 4。晶体结构用直接法解出 ,经全矩阵最小二乘法对原子参数进行修正 ,最终的偏离因子为R =0 .0 4 1 6,wR =0 .1 1 75。在晶体结构中 ,二氢吡啶环与苯环之间的二面角为 92 .1 4°。     

Bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (foridone)

The action of mild brominating agents (pyridinium bromide-perbromide, dioxan dibromide N-bromosuccinimide, and N-bromoacetamide) on 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine (Foridone) has been studied. Depending on reaction conditions, furo-, difuro-, and dibromomethyl-1,4-dihydropyridines are obtained together with certain oxidized forms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 948–952, July, 1989.     

Chlorination of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (phoridone)

Chlorination of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine gives 2,3,4,5-tetrahydropyridines with different degrees of chlorination dependent upon the quantitative ratio of reagents. The reaction proceeds without oxidation of the dihydropyridine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 376–379, March, 1990.     

The synthesis of some dialkyl 4-(3-substituted amino)phenyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates

Dialkyl 4-(3-aminophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 1 were transformed into alkyl 4-(3-(((2-benzoylamino-2-methoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 4 and with 2,2-disubstituted-1-dimethylaminoethenes 7 into dimethyl 4-(3-(((2,2-diacyl- or 2-acyl-2-alkoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 8 and their ethyl methyl analogues 9.     

Rearrangements of 4-(2-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid diethyl ester

The treatment of 4-(2-aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylic acid diethyl ester (III) with refluxing toluene or pyridine afforded 1,2,3,6-tetrahydro-2,4-dimethyl-2,6-methano-1,3-benzodiazocine-5,11-dicarboxylic acid diethyl ester (IV) as the major product. In addition, the following minor products were isolated: 2-methyl-3-quinolinecarboxylic acid ethyl ester (V), 3-(2-aminophenyl)-5-methyl-6-azabicyclo[3,3,1]-hept-1-ene-2,4-dicarboxylic acid diethyl ester (VI), and 5,6-dihydro-2,4-dimethyl-5-oxobenzo[c][2,7]naphthyridine-1-carboxylic acid ethyl ester (VII). In contrast, acidic conditions caused the conversion of III into V in a 95% yield. The formation of the latter appears to involve IV as an intermediate, since IV degraded rapidly in acid to give V in a quantitative yield.     

Bromination of 4-aryl-3,5-dialkoxycarbonyl-2,6-dimethyl-1,4-dihydropyridines

4-Aryl-3,5-dialkoxycarbonyl-2,6-dimethyl-1,4-dihydropyridines are brominated by N-bromosuccinimide in methanol at room temperature at the methyl groups at positions 2 and 6 to form mono-, di-, tri-, and tetrabromo derivatives. When the N-unsubstituted bromomethyl-1,4-dihydropyridines are heated they are easily converted to tetrahydrofuropyridines, but in the case of the analogous N-substituted-1,4-dihydropyridines cyclization does not occur. The 2,6-bis(bromomethyl)-substituted products easily replace bromine under the influence of nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1230–1235, September, 1991.     

1,4-二氢-4-芳基-3,5-吡啶二羧酸酯的合成及表征

基于二氢吡啶化合物的构效关系, 设计了一系列1,4-二氢-4-芳基-3,5-吡啶二羧酸酯新化合物. 含有易于水解基团的1,4-二氢-4-芳基-3,5-吡啶二羧酸酯类化合物在碱性条件下水解合成了重要中间体1,4-二氢-4-芳基-3,5-吡啶二羧酸单酯, 收率93%～99.8%. 该二羧酸单酯与α-溴代芳基乙酮在相转移剂催化下反应合成目标化合物, 收率74%～99%. 中间体和目标化合物经¹H NMR, ¹³C NMR, IR, MS和元素分析等确证.     

Mechanism of the antioxidant action of 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2-nitrophenyl)1,4-dihydropyridine

A comparison of data on the kinetics of the accumulation of peroxides and the ESR spectra in the case of inhibition of the autooxidation of methyl oleate by 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2-nitrophenyl)1,4-dihydropyridine (I) established that the antioxidant action of the latter is exerted by the formation of a nitroxyl radical. This radical is produced analogously to the well-known scheme from 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2-nitrosophenyl)pyridine, which is generated in the reaction medium from I and methyl oleate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1120–1122, August, 1984.     

New derivatives of 4-aryl-2,6-dimethyl-3,5-diacetyl-1,4- and 1,2-dihydropyridines

4-Aryl-1,2,6-trimethyl-3,5-diacetyl-1,4-dihydropyridines and the corresponding pyridinium salts, which upon reduction with NaBH₄ form 4-aryl-1,2,6-trimethyl-3,5-diacetyl-1,2-dihydropyridines, were synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 508–513, April, 1983.