Regioselectivity of 1,3-dipolar cycloadditions and antimicrobial activity of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-diones, pyrazolo[3,4-d]pyridazines and pyrazolo[1,5-a]pyrimidines

Abstract

BackgroundIsoxazoles exhibit interesting biological activities, and the 1,3-dipolar cycloaddition(13DC) reactions play an important role in both mechanistic and synthetic organic chemistry. Pyrazoles and annulated pyrazoles exhibit some diverse biological activities. They are used as antipyretic, analgesic drugs, tranquilizing, and herbicidal agents. Pyrazoles are also used extensively as useful synthons in organic synthesis. Pyrazolo[3,4-d]pyridazines showed good antimicrobial, anti-inflammatory and analgesic activities. Several oximes are found to be hyperglycemic, anti-neoplastic, anti-inflammatory, anti-leishmanial and VEGFR-2 kinase inhibitors.ResultsThe present work describes an efficient synthesis protocol and molecular orbital calculations of isoxazoline and pyrrolo[3,4-d]isoxazole-4,6-dione derivatives from the reaction of hydroximoyl chloride with acrylonitrile, acrylamide, and N-arylmalemides. In addition, pyrazoles and pyrazolo[3,4-d]pyridazines are obtained via the reaction of 3-(dimethylamino)-1-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-ene-1-one with hydrazonoyl halides. Pyrazolo[1,5-a]pyrimidines were derived from condensation of either Sodium Salt of 3-Hydroxy-1-(2,4-dimethylthiazol-5-yl)prop-2-en-1-one (10) or 3-(dimethylamino)-1-(2,4-dimethyl)(1,3-thiazol-5-yl)prop-2-en-1-one (11) with aiminopyrozoles. A comparative study of the biological activity of the synthesized compounds with ampicillin and tetracycline is compiled in Table 3. Generally, all synthesized compounds showed an adequate inhibitory efficiency of growth of gram-positive and gram-negative bacteria. Structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data and a computational study.ConclusionsIn summary, new and efficient synthetic routes of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-dione derivatives, pyrazoles, pyrazolo[3,4-d]pyridazines and pyrazolo[1,5-a]pyrimidines have been achieved and the biological activity has been investigated.Graphical abstractNew and efficient synthetic routes of isoxazoline, pyrrolo[3,4-d]isoxazole-4,6-dione derivatives, pyrazolo[3,4-d]pyridazines and pyrazolo [1,5-a] pyrimidines

Synthesis of Piperine Analogs Containing Isoxazoline/Pyrazoline Scaffold and Their Pesticidal Bioactivities

“…Piperine (Figure ) is isolated as a simple alkaloid from Piper nigrum Linn. and exhibits lots of biological properties such as anti-inflammatory, antimicrobial, antitumor, and pesticidal activities. , In addition, molecules containing an isoxazoline ( I ) or pyrazoline ( II , Figure ) fragment show antimicrobial, fungicidal, mosquitocidal, anti-Alzheimer, anticancer, monoamine oxidase inhibitory, pesticidal, and/or anti-inflammatory activities. − Previously, we studied isoxazolopodophyllic acid-based esters ( III , Figure ), isoxazolopodophyllol-based esters ( IV , Figure ), and isoxazolopodophyllal-based hydrazones ( V , Figure ) from podophyllotoxin and found that some derivatives showed more promising insecticidal activity than toosendanin, a commercial botanical insecticide isolated from Melia azedarach . , Based upon the above results, and in continuation of our program aimed at the development of new potential pesticidal agents, − therefore, a series of piperine analogs containing isoxazoline/pyrazoline scaffold ( VI – IX , Figure ) were prepared. Their insecticidal and acaricidal activities were evaluated against M. separata , T. cinnabarinus , and P. xylostella .…”

Structural Elucidation and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[4,3‐a]pyrimidines and Pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones

“…They have been reported as antitumor and antileukemia activity , antimicrobial, antiviral , anti‐inflammatory , anti‐HIV , antitubercular , antineoplastic , antimalarial , diuretic , cardiovascular agents , hypnotic drugs for the nervous system , and also for antagonists of the human A2A adenosine receptor . In this paper, and in continuation of our previous research work aiming at the synthesis of a variety of heterocyclic systems with the remarkable biological importance, we used a simple, facile, efficient, and one‐pot procedure for the synthesis of different pyrimidine and fused pyrimidine derivatives using available and easily prepared to starting materials such as pyrimidinethiones and hydrazonyl halides.…”

[3 + n] Cycloaddition Reactions: A Milestone Approach for Elaborating Pyridazine of Potential Interest in Medicinal Chemistry and Optoelectronics

“…Zaki et al [ 39 ] synthesized a series of pyrazolo[3,4-d]pyridazines 50a – c , as shown in Scheme 13 . In order to obtain the desired compounds 50a – c , initially they obtain the pyrazole derivatives 49a – c using the cycloaddition reaction of the nitrile imines 47a – c (generated in situ by the action of the base TEA on the hydrazonoyl chlorides 46a – c ) with thiazole derivative 48 , followed by a cyclocondensation with hydrazine.…”