Directed Search of Anti-inflammatory Agents Among (3H-Quinazoline-4-ylidene)hydrazides of N-protected Amino acids and their Heterocyclization Products
| Autor: | Oleksii M. Antypenko, Sergii Ivanovich Kovalenko, I. S. Nosulenko, G. G. Berest, Yulya Martynenko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
Immunology Anti-Inflammatory Agents 010402 general chemistry Mass spectrometry 01 natural sciences Medicinal chemistry Anti-inflammatory chemistry.chemical_compound Residue (chemistry) [1 2 4]triazolo [1 5-c]quina-zolines Formaldehyde medicine Immunology and Allergy Animals Edema Amino Acids Rats Wistar anti-inflammatory activity (3H-quinazoline-4-ylidene)hydrazides N-protected amino acids Pharmacology chemistry.chemical_classification 010405 organic chemistry Aryl General Medicine Diclofenac Sodium Nuclear magnetic resonance spectroscopy molecular docking 0104 chemical sciences Amino acid Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Molecular Docking Simulation Hydrazines chemistry SAR-analysis Cyclization Cyclooxygenase 2 Cyclooxygenase 1 Quinazolines Linker heterocyclization products |
| Zdroj: | Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry |
| ISSN: | 1875-614X 1871-5230 |
| Popis: | Background: (Quinazoline-4-ylidene)hydrazides are valued intermediates in modern organic chemistry, as they are commonly used for the synthesis of substituted [1,2,4]triazolo[1,5-c]quinazolines. Objective: Unknown N-acyl-2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl)-alkyl-(alkaryl-, aryl-) amines were synthesized and evaluated for anti-inflammatory potential. Methods: The peculiarities of the synthesized compounds structures were studied by IR-, NMR spectroscopy and chromatography-mass spectrometry and were discussed in detail. Probable molecular mechanisms of activity (inhibition of COX-1 and COX-2) were predicted due to molecular docking. Anti-inflammatory activity of synthesized compounds was determined by their ability to reduce the formalin-induced paw edema in rats. Diclofenac sodium was used as reference drug. Results: In this study, the synthesis of N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5-c]quinazolinе- 2-yl)alkyl-(aralkyl-, aryl-)amines, using (3H-quinazoline-4-ylidene)hydrazides of Nprotected amino acids or 4-hydrazinoquinazoline and N-prorotected amino acids as starting compounds was developed. It was established that the reaction of (3H-quinazoline-4- ylidene)hydrazides of Boc-amino acids occurred with the formation of N-acetyl-substituted triazoloquinazolines. High anti-inflammatory activity was detected for unknown (3Hquinazoline- 4-ylidene)hydrazides Boc-amino acids (1.13-1.15) and N-acetyl-(benzoyl)-2- ([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)aralkyl-(aryl-)amines (3.2, 3.3, 3.11, 3.12), using the experimental formalin test. Conclusion: The conducted SAR-analysis allowed to detect critical fragments. Namely, the Boc-aminoaralkyl-(aryl-)acid residue in (3H-quinazoline-4-ylidene)hydrazides (1.13- 1.15), benzyl and phenyl linker groups in N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5- c]quinazoline-2-yl-)aralkyl-(aryl-) amines (3.2, 3.3, 3.11, 3.12) are believed to be substantial for anti-inflammatory activity. |
| Databáze: | OpenAIRE |
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