Синтез та антимікробна активність 5-арокси-2,6-дигідро-1Н-піроло[3,4-d]піридазин-1-онів

• Date: 2019
• Main Authors: Grozav, A. M., Fedoriv, M. Z., Chornous, V. O., Yakovychuk, N. D., Deineka, S. Ye., Kemskyi, S. V.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2019
• Subjects: поліфункціональні піроли; гідразин-гідрат; піридазиноанелювання; 1Н-піроло[3; 4-d] піридазин-1-они; антибактеріальна та протигрибкова активність; УДК 547.745 547.562.4 547.852 615.31
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.19.970
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

Aim. To develop an effective method for the synthesis of 5-aroxy-2,6-dihydro-1Н-pyrrolo[3,4-d]pyridazine-1-ones as promising objects to be investigated in the context of their antimicrobial activity.Results and discussion. It has been found that ethyl 4-formyl-5-chloro-1Н-pyrrole-3-carboxylates can be used as convenient source substrates for building 5-aroxy-2,6-dihydro-1Н-pyrrolo[3,4-d]pyridazine-1-one systems. MBsC (MFsC) and MBcC (MFcC) of the pyrrolo[3,4-d]pyridazine-1-ones synthesized were within the rangeof 31.25-125 μg/ml.Experimental part. The two-stage synthesis of 5-aroxy-2,6-dihydro-1Н-pyrrolo[3,4-d]pyridazine-1-ones was performed. The chemical composition and the structure of the compounds synthesized were confirmed by chromatography-mass spectra, IR- and NMR 1Н (13С) spectra. The screening of the antimicrobial activity using the micromethod of the double series dilutions in the liquid nutrient medium allowed identifying compounds with a moderate activity.Conclusions. A preparative convenient synthesis of 5-aroxy-2,6-dihydro-1Н-pyrrolo[3,4-d]pyridazine-1-ones has been developed. This method assumes the nucleophilic substitution of the chlorine atom in ethyl 4-formyl-5-chloro-1Н-pyrrole-3-carboxilates with an aroxyl fragment followed by the subsequent pyridazinoanelination ofethyl 5-aroxy-4-formyl-1Н-pyrrole-3-carboxylates by hydrazine hydrate. The results of the antimicrobial activity of the substances synthesized substantiate the feasibility of further in-depth studies in this area.