Yulya Martynenko 1 , Oleksii Antypenko 1 , Inna Nosulenko 2 , Galina Berest 3 , Sergii Kovalenko 1 Show Affiliations »
Abstract
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: (Quinazoline-4-ylidene)hydrazides are valued intermediates in modern organic chemistry, as they are commonly used for the syn thesis 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 syn thesized and evaluated for anti-inflammatory potential. METHODS: The peculiarities of the syn thesized compounds structures were studied by IR-, N MR 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 syn thesized 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 syn thesis of N -acetyl -(benzoyl)-2-([1,2,4]triazolo[1,5-c]quinazolinе- 2-yl)alkyl-(aralkyl-, aryl-)amine s, 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. N amely, 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-) amine s (3.2, 3.3, 3.11, 3.12) are believed to be substantial for anti-inflammatory activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: CellLine
Chemical
Disease
Gene
Species
Keywords:
(3H-quinazoline-4-ylidene)hydrazides N-protected amino acids; SAR-analysis; [1,2,4]triazolo[1,5-c]quinazolines; anti-inflammatory activity; heterocyclization products; molecular docking.
Year: 2020
PMID： 30648525 DOI： 10.2174/1871523018666190115092215
Source DB: PubMed Journal: Antiinflamm Antiallergy Agents Med Chem ISSN： 1871-5230