Chemistry of dihydropyridines

Eisner, Ulli; Kuthan, J.

doi:10.1021/cr60275a001

Cited by 811 publications

(288 citation statements)

References 77 publications

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“…The wavelength of ultraviolet absorption maxima are lower for the reduced 5-methyl dinucleosides than for the reduced forms of the model compounds. The same observation has been made for NADH and dihydronicotinamide derivatives [20]. cn ' m PdAD …”

Section: Preparation and Properties Of Model Compounds And Of 5-methysupporting

confidence: 70%

5-Methylnicotinamide-adenine Dinucleotide. Kinetic Investigation with Major and Minor Isoenzymes of Liver Alcohol Dehydrogenase and Structural Determination of Its Binary Complex with Alcohol Dehydrogenase

1981

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5-Methylnicotinamide -adenine dinucleotide and 3-cyano-5-methylpyridine -adenine dinucleotide were prepared from 5-methylthionicotinamide -adenine dinucleotide by chemical conversion. The 5-methylthionicotinamide -adenine dinucleotide was obtained by enzymic transglucosidation. Model compounds ascertained the structure. None of the dinucleotides rnethylated at C-5 was active with the major isoenzyme EE of horse liver alcohol dehydrogenase, but activity with 5-methylnicotinaniide -adenine dinucleotide was measured with the minor isoenzymes. The binding of 5-methylnicotinamide -adenine dinucleotide to liver alcohol dehydrogenase, investigated by X-ray diffraction methods to 0.37-nm resolution, occurs with the pyridinium ring away from the active site as previously described for 3-iodopyridine -adenine and pyridine -adenine dinucleotides. A general conclusion on the use of inhibitors as tools for exploration of the active site is drawn.The X-ray structure determination of the orthorhombic apoenzyme of the alcohol dehydrogenase from horse liver [I] prompted the study of the binding of coenzyme or coenzyme analogues and substrates to clarify the binding mode and the reaction mechanism. It has been shown previously that when an oxidized or a reduced coenzyme is soaked into these crystals, they crack and dissolve. Crystallisation of ternary eiizyme-NADH-substrate complexes gives triclinic or monoclinic crystals with a different conformation of the enzyme molecule [2]. During a screening of coenzyme analogues it was found that 5-methylnicotinamide-adenine dinucleotide (m5NAD)+ did not induce cracking of the orthorhombic crystals in spite of earlier reports that this analogue showed activity as an hydride acceptor [3]. This apparent discrepancy between the activity and absence of crystal cracking prompted us to carry out a more thorough chemical and biochemical study of this analogue and of model compounds. We report here the results of our chemical and biochemical investigations and the structure determination at 0.37-nm resolution of the orthorhombic binary complex alcohol dehydrogenase-m5NAD+. A study of m5NAD+ with lactate dehydrogenase has been reported recently [4]. Enzymes. Alcohol dehydrogenase (EC 1.1.1.1); lactate dehydrogenase (EC 1 .I .1.27); NAD(P)+ glycohydrolase (EC 3.2.2.6); glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). MATERIALS AND METHODS 5- MODEL COMPOUNDS3-Cyano-5-methylpyridine (1). A suspension of 5-methylnicotinamide (3 g) in phosphorous oxychloride ( 5 ml) was heated under reflux for 45 min. After cooling, the excess of reagent was removed under reduced pressure and the mixture poured into a concentrated sodium carbonate solution and extracted thrice with chloroform. The extract was dried over sodium sulfate. Removal of the solvent under reduced pressure gave a solid which was sublimed (65°C under 1.33 Pa). The 3-cyano-5-methyl pyridine (I) was obtained as white crystals (1.93 g, yield 74%): m.p. 82-84°C (cf. 83-84°C [6]). ' H NMR (C'HCI,): 6 = 2.43 ppm (3H), 7.81 ppm (IH) and 8.69 p...

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Section: Preparation and Properties Of Model Compounds And Of 5-methysupporting

confidence: 70%

5-Methylnicotinamide-adenine Dinucleotide. Kinetic Investigation with Major and Minor Isoenzymes of Liver Alcohol Dehydrogenase and Structural Determination of Its Binary Complex with Alcohol Dehydrogenase

1981

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“…In the laboratory Hantzsch pyridines [9][10][11][12][13] are readily prepared by a two-step sequence (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

New pyridine-containing non-cyclic and macrocyclic Schiff bases: synthesis and interferon-inducing activity

Lozytska¹,

Kryzhanovsky²,

Gorodniuk³

et al. 2004

Arkivoc

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A series of new Schiff bases containing the Hantzsch pyridine skeleton has been synthesized by reaction of an appropriate aldehyde with 2,6-dimethyl-3,5-pyridinedicarboxhydrazide. The structure of the final products, which was highly dependent on the nature of the starting aldehyde, could readily be ascertained by their spectral data. 2,6-Dimethyl-3,5-pyridinedicarboxhydrazide itself and some of its derivatives emerged as potential interferon inducers.

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“…1 The chemical modifications carried on the DHP ring such as variation of different substituents 2 or heteroatoms 3 have allowed expansion of the structure activity relationship and afforded some insight into the molecular interactions at the receptor level. Recently there are many methods available for synthesis tricycle compounds containing the 1,4-dihydropyridines, such as acridine derivatives, from aldehyde, dimedone and ammonium acetate via traditional heating in organic solvents, 4 or in water catalyzed by triethylbenzylammonium chloride TEBAC, 5 or improved under microwave irradiation, 6 or by green chemistry in ionic liquids.…”

Section: Introductionmentioning

confidence: 99%

A clean procedure for synthesis of benzo[c]acridine derivatives: reaction of N-arylidenenaphthalen-1-amine with 5,5-dimethyl-1,3-cyclohexadione in aqueous medium

Wang¹,

Zhang²,

Zeng³

et al. 2006

Arkivoc

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Chemistry of dihydropyridines

Cited by 811 publications

References 77 publications

5-Methylnicotinamide-adenine Dinucleotide. Kinetic Investigation with Major and Minor Isoenzymes of Liver Alcohol Dehydrogenase and Structural Determination of Its Binary Complex with Alcohol Dehydrogenase

5-Methylnicotinamide-adenine Dinucleotide. Kinetic Investigation with Major and Minor Isoenzymes of Liver Alcohol Dehydrogenase and Structural Determination of Its Binary Complex with Alcohol Dehydrogenase

New pyridine-containing non-cyclic and macrocyclic Schiff bases: synthesis and interferon-inducing activity

A clean procedure for synthesis of benzo[c]acridine derivatives: reaction of N-arylidenenaphthalen-1-amine with 5,5-dimethyl-1,3-cyclohexadione in aqueous medium

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