Synthesis, biological evaluation and molecular modelling studies on benzothiadiazine derivatives as PDE4 selective inhibitors

Autor: Amedeo Luppi, Hatzelmann Armin, Paola Fossa, Annalisa Tait, Luisa Mosti
Rok vydání: 2005
Předmět:
Models
Molecular
Magnetic Resonance Spectroscopy
Biological Evaluation and Molecular Modeling Studies
Spectrophotometry
Infrared
Molecular model
Phosphodiesterase Inhibitors
Clinical Biochemistry
Pharmaceutical Science
In Vitro Techniques
Benzothiadiazines
Biochemistry
Chemical synthesis
Cell Line
Synthesis
Pulmonary Disease
Chronic Obstructive
chemistry.chemical_compound
Drug Discovery
PDE4inhibitors
Humans
Moiety
Potency
Molecular Biology
Phosphodiesterase 4
DNA Primers
chemistry.chemical_classification
Chronic inflammatory diseases
Base Sequence
biology
Organic Chemistry
Asthma
In vitro
Cyclic Nucleotide Phosphodiesterases
Type 4
Benzothiadiazine Derivatives
PDE4
Benzothiadiazine
Enzyme
chemistry
3'
5'-Cyclic-AMP Phosphodiesterases
Enzyme inhibitor
biology.protein
Molecular Medicine
Antioxidant
Zdroj: Bioorganic & Medicinal Chemistry. 13:1393-1402
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2004.10.055
Popis: A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoforms PDE3, PDE4 and PDE7. The compounds characterized by the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N1 position of 2,1,3-benzothiadiazine core (8, 13, 18), were found active and selective at micromolar level versus PDE4 and could be studied as new leads for the treatment of asthma and COPD (Chronic Obstructive Pulmonary Disease). The antioxidant activity evaluation on the same compounds highlighted 13 as the most significative. Molecular modelling studies gave further support to biological results and suggested targeted modifications so as to improve their potency.
Databáze: OpenAIRE
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