+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Synthesis and cardiotonic activity of esters of 2 substituted 5 cyano 1 6 dihydro 6 oxo 3 pyridinecarboxylic acids crystal structure of 2 methyl 2 tert butyl and 2 phenyl esters

Synthesis and cardiotonic activity of esters of 2 substituted 5 cyano 1 6 dihydro 6 oxo 3 pyridinecarboxylic acids crystal structure of 2 methyl 2 tert butyl and 2 phenyl esters

European Journal of Medicinal Chemistry 24(5): 517-530

ISSN/ISBN: 0223-5234

The synthesis of ethyl and methyl esters of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids by reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with sodium cyanoacetamide is described. These esters gave by alkaline hydrolysis the corresponding carboxylic acids, which were decarboxylated to 6-substituted 1,2-dihydro-2-oxo-3-pyridinecarbonitriles. As milrinone analogues, nearly all the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria and electrically driven left atria from guinea pigs. Among the esters, ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3-pyridinecarboxylate induced positive inotropic and chronotropic effects superior to those caused by milrinone. By increasing or branching the 2-substitutent, the activity decreased until faded or even reversed. Carboxylic acids and nitriles were less active than milrinone. Some aspects of the structure-activity relationship of these compounds are discussed on the basis of X-ray structural analyses of 2-methyl, 2-t-butyl and 2-phenyl esters.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 007855189

Download citation: RISBibTeXText

Related references

Synthesis and cardiotonic activity of esters of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarylic acids. Crystal structure of 2-methyl, 2-t-butyl and 2-phenyl esters. European Journal of Medicinal Chemistry 24(5): 517-529, 1989

Synthesis and cardiotonic activity of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids and their methyl or ethyl esters. Farmaco 47(4): 427-437, 1992

Synthesis and cardiotonic activity of esters of 2-substituted 5-acetyl-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids. European Journal of Medicinal Chemistry 28(11): 853-858, 1993

Synthesis of polyamic acid di-tert-butyl esters by direct polycondensation of di-tert-butyl esters of tetracarboxylic acids with diamines using diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate. die Makromolekulare Chemie 194(2): 511-521, 1993

Synthesis and biological activity of novel calcium channel blockers: 2,5-dihydro-4-methyl-2-phenyl-1,5-benzothiazepine-3-carboxylic acid esters and 2,5-dihydro-4-methyl-2-phenyl-1,5-benzodiazepine-3-carboxylic acid esters. Journal of Medicinal Chemistry 30(4): 635-640, 1987

Crystal structure and catalytic activity of tetra-kis-(μ 2 -ethyl 2,6-di- tert -butyl-4-methyl-phenyl phos-phato-κ 2 O : O ')bis-(ethyl 2,6-di- tert -butyl-4-methyl-phenyl phosphato-κ 2 O , O ')dilutetium n -heptane disolvate. Acta Crystallographica. Section E Crystallographic Communications 74(Pt 4): 543-547, 2018

Synthesis of methyl esters of uronic acids 2. synthesis of 2 3 di o methyl esters 2 4 di o methyl esters 3 4 di o methyl esters and 2 3 4 tri o methyl esters of methyl methyl alpha d galacto pyranoside uronate. Khimiya Prirodnykh Soedinenii 1982(3): 283-285, 1982

Structure elucidation of methyl esters of cyclic fatty acids part 4 occurrence of methyl esters of omega phenyl alkanoic acids in cyclized tung d and lin seed d oil. Fette Seifen Anstrichm 71(8): 633-636, 1969

Elucidation of structure of the methyl esters of cyclic fatty acids part 5 mass spectrometry of isomeric methyl esters of phenyl undecanoic acid. Fette Seifen Anstrichm 71(10): 880-888, 1969

Synthesis, crystal structures, insecticidal activities, and structure--activity relationships of novel N'-tert-Butyl-N'-substituted-benzoyl-N-[di(octa)hydro]benzofuran{(2,3-dihydro)benzo[1,3]([1,4])dioxine}carbohydrazide derivatives. Journal of Agricultural and Food Chemistry 59(2): 635-644, 2011

NMR study of the conformational distribution in methyl esters and N,N-dimethylamides of diastereoisomeric 4-cyano-3,4-diphenyl- and 4-cyano-3-phenyl-4-(1-naphthyl)-butyric acids. Relation to the configurations. Journal of Molecular Structure 271(4): 251-260, 1992

Potentielle Kardiotonika. II: Synthese und pharmakologische Eigenschaften von 5-(pyrid-4-yl)- und 5-phenylsubstituierten 3-Cyan-6-methyl-2-oxaalkylamino-pyridinen - Cardiotoniques potentiels. II: Synthèse et propriétés pharmacologiques de cyano-3 méthyl-6 oxaalkylamino-2 pyridines substituées en [pyridyl-4]-5 et phényl-5 - Potential cardiotonic agents. II: Synthesis and pharmacological properties of 5-(4-pyridinyl)- and 5-phenyl-substituted 3-cyano-6-methyl-2-oxaalkylamino-pyridines. Pharmazie 44(1): 23-25, 1989

An improved synthesis of 1 3 dihydro 1 methyl 5 phenyl 2h pyrido 3 4 e 1 4 diazepin 2 one via ortho directed lithiation of 3 tert butyl and 3 tert butoxycarbonylaminopyridine. Canadian Journal of Chemistry 65(6): 1158-1161, 1987

Synthesis and in-vitro antimycobacterial evaluation of 1-(cyclopropyl/2,4-difluorophenyl/tert-butyl)-1,4-dihydro- 8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids. Archiv der Pharmazie 342(2): 100-112, 2009

Darstellung von 3-cyan-4-methyl-6-(un)substituiertphenyl- und 3-cyan-6-methyl-4-(un)substituiertphenyl-pyrid-2(1H)-thionen und -onen - Synthèse de cyano-3 méthyl-4 phényl-6 (et phénylsubstitué-6)- et de cyano-3 méthyl-6 phényl-4 (et phényl substitué-4) 1H-pyridinethiones- et -ones-2 - Synthesis of 3-cyano-4-methyl-6-(un) substituted-phenyl-pyrid-2(1H)-thiones and -ones. Pharmazie 41(12): 827-830, 1986