[Benzo[c][2,7]naphthyridines from 2,6-dinor-nifedipine and its dimethyl 2,5-dicarboxylate isomer].

Abstract

The reaction of 2-nitrobenzaldehyde with methyl propiolate and ammonium acetate in acetic acid yields 2,6-dinor-nifedipine (1a) and the isomeric rac. 1,4-dihydropyridine (DHP) 1b. The DHP 1 are dehydrogenated both chemically and by anodic oxidation using a rotating platinum electrode (RPE) by means of differential pulse voltammetry (DPV) affording the corresponding pyridines 2a, b. Compound 1a is more stable, while compound 1b is less stable than nifedipine. Irradiation of the DHP 1 with UV-A light forms the nitrosophenyl-pyridines 3, which cyclize after addition of conc. hydrochloric acid to yield the chloro substituted hydroxamic acids 4a, b. The hydroxamic acids 4c, d are obtained treating 2a, b with zinc in acetate buffer pH 4.6. The hydroxamic acids 4b, d demonstrate only a moderate inhibition of 5-lipoxygenase (5-LOX) of human whole blood compared with the activity of the reference compound zileutone. The formation of 15-HETE is also inhibited. Compound 4a reduces the activity of cyclooxygenase. The lactames 5, obtained from the hydroxamic acids 4 by desoxygenation with phosphorus trichloride, react with phosphoryl chloride to give compounds 6, representing educts for potential agents against malaria.

• Authors: K Görlitzer, M Bode, P Frohberg, G Drutkowski
• Journal: Die Pharmazie (Pharmazie) Vol. 59 Issue 1 Pg. 15-20 (Jan 2004) ISSN: 0031-7144 [Print] Germany
• Vernacular Title: Benzo[c][2,7]naphthyridine aus 2,6-Dinor-nifedipin und dessen 2,5-Dicarbonsäuredimethylester-Isomer.
• PMID: 14964415 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antimalarials
• Hydroxamic Acids
• Hydroxyeicosatetraenoic Acids
• Indicators and Reagents
• Lipoxygenase Inhibitors
• Naphthyridines
• Arachidonic Acid
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Arachidonate 5-Lipoxygenase
• Nifedipine
• Zinc
• Hydrochloric Acid

Topics

• Antimalarials (chemical synthesis, pharmacology)
• Arachidonate 5-Lipoxygenase (blood)
• Arachidonic Acid (blood)
• Cyclization
• Electrochemistry
• Humans
• Hydrochloric Acid
• Hydroxamic Acids (chemistry)
• Hydroxyeicosatetraenoic Acids (chemistry)
• In Vitro Techniques
• Indicators and Reagents
• Isomerism
• Lipoxygenase Inhibitors (chemical synthesis, pharmacology)
• Naphthyridines (chemistry)
• Nifedipine (chemistry)
• Oxidation-Reduction
• Ultraviolet Rays
• Zinc