Abstract
A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives 3 were formed as the sole isolable products in excellent yield. The 6-acetyl-3-oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding enaminone derivative 4, which reacts with a variety of aminoazoles to afford the corresponding azolo[1,5-a]pyrimidine derivatives 5–7. Also, in order to explore the viability and generality of a recently uncovered reaction between 3-oxo-2-arylhydrazonopropanals and active methylene compounds, a variety of 2-amino-6-aryl-5-arylazo-3-aroylpyridines 16–19 were prepared by reacting 3-oxo-2-arylhydrazonopropanals with miscellaneous active methylene compounds like 3-oxo-3-phenylpropionitrile, hetaroylacetonitriles and cyanoacetamides. These 2-aminopyridine derivatives undergo smooth reactions with cyanoacetic acid that led to the formation in high yield of a new class of 1,8-naphthyridine derivatives 24. The structures of all new substances prepared in this investigation were determined by the different analytical spectroscopic methods, in addition to the X-ray crystallographic analysis.
Highlights
Nitrogen-containing heterocyclic compounds have a diverse range of biological and pharmacological properties [1,2,3]
Pyridazine and pyridine derivatives are two of the most important heterocycles found in medicinal chemistry as they have an excellent biological activity with a wide range of applications, including antimicrobial [4,5,6], antiinflammatory and analgesic [7,8,9], anti-HIV [10], antiplasmodial [11], antitubercular [3,12], antibacterial [3,13], anticonvulsant [14,15], COX inhibitor [16], antidiabetic [17], antihypertensive [18,19], anticancer effects [20,21,22,23,24], blood platelet aggregation inhibitors [25], antidepressant and anxiolytic [26,27], antioxidant [28], antitumor [29,30] and antifungal activities [31]
Recent efforts in our laboratories have led to the design of new and general strategies for the preparation of 2-amino-5-arylazonicotinates and pyridazinones [37] that involve reactions of 3-oxo-2-arylhydrazonopropanals 1 with active methylene compounds, including ethyl cyanoacetate, and malononitrile, depending on the effect of the substituent present in the arylazo moiety
Summary
Nitrogen-containing heterocyclic compounds have a diverse range of biological and pharmacological properties [1,2,3]. Pyridazine and pyridine derivatives are two of the most important heterocycles found in medicinal chemistry as they have an excellent biological activity with a wide range of applications, including antimicrobial [4,5,6], antiinflammatory and analgesic [7,8,9], anti-HIV [10], antiplasmodial [11], antitubercular [3,12], antibacterial [3,13], anticonvulsant [14,15], COX inhibitor [16], antidiabetic [17], antihypertensive [18,19], anticancer effects [20,21,22,23,24], blood platelet aggregation inhibitors [25], antidepressant and anxiolytic [26,27], antioxidant [28], antitumor [29,30] and antifungal activities [31]. For example Isoniazide and Amlodipine are two drugs containing the pyridine motif as anti-tuberculosis and anti-hypertensive respectively (Figure 1). On the basis of the above findings the pyridine and pyridazine moieties are considered privileged structures and, they have attracted the general and continuing interest of synthetic organic chemists
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