Abstract
This work describes the utility of pyrazole-4-carbaldehyde 1 as starting material for the synthesis of a novel potent series of 5α-reductase and aromatase inhibitors derived from 1,2,3-triazole derivative. Condensation of 1 with active methylene and different amino pyrazoles produced the respective Schiff bases 2–4, 8 and 9. On the other hand, 1 was reacted with ethyl cyanoacetate and thiourea in one-pot reaction to afford the pyrazolo-6- thioxopyridin-2-[3H]-one (10). Moreover, α–β unsaturated chalcone derivative 11 was prepared via the reaction of compound 1 with P-methoxy acetophenone, which in turn reacted with each of ethyl cyanoacetate, malononitrile, hydrazine hydrate, and thiosemicarbazide to afford the corresponding pyridine and pyrazole derivatives 13, 14, 17, and 20. The structure of newly synthesized compounds was characterized by analytical and spectroscopic data (IR, MS and NMR). All new compounds were evaluated against 5α-reductase and aromatase inhibitors and the results showed that many of these compounds inhibit 5α-reductase and aromatase activity; compound 13 was found to be the highest potency among the tested samples comparing with the reference drugs.
Highlights
The starting compound 1 will react with appropriate active methylene to give compounds 2–4, while, a newly substituted pyrazole derivative 5–9 will be formed when compounds 2–4 react with hydrazine
Chalcone derivative 11 is prepared via the reaction substituted pyrazole 1 with P-methoxy acetophenone, which in turn reacts with each of ethyl cyanoacetate, malononitrile hydrazine hydrate, and thiosemicarbazide to give the corresponding pyridine and pyrazole derivatives 13, 14, 17, and 20, respectively
Results of the present study demonstrate that compound 1 reacts with different active methylene and amino pyrazoles to yield a new series of pyrazole derivatives derived from 1,2,3-triazole derivative
Summary
The pharmaceutical importance of 1,2,3-triazole ring is due to its efficacy as c-Met kinase inhibitors [1], aromatase inhibitors [2], 5α-reductase inhibitors [3], virostatic [4], antiproliferative agents [5,6,7], GABA-antagonists [8], antimicrobial agents [9,10], anti-bacterial agents [11], novel inhibitors of human immunodeficiency virus type protease [12], glycosidase inhibitors, antimalarial agents [13], antihistaminic agents [14], nucleosides [15], as synthetic intermediates for some antibiotic compounds [16], and for treatment of Alzheimer’s disease [17].On the other hand, pyrazoline derivatives are a very important class of heterocyclic compounds characterized by biological activities as antiviral [18], anticancer [19], antimicrobial agent [20], 5α-reductase, and aromatase inhibitors [21,22].We are incorporated in a research group aimed to produce biologically active heterocyclic compounds using available chemicals [5,6,23,24,25,26,27,28,29,30,31]. Pyrazoline derivatives are a very important class of heterocyclic compounds characterized by biological activities as antiviral [18], anticancer [19], antimicrobial agent [20], 5α-reductase, and aromatase inhibitors [21,22]. Our growing interest in this manuscript is incorporation between 1,2,3-triazole ring and pyrazoline ring in a new heterocyclic compound 1 [5]. The starting compound 1 will react with appropriate active methylene to give compounds 2–4, while, a newly substituted pyrazole derivative 5–9 will be formed when compounds 2–4 react with hydrazine. The newly synthesized compounds were evaluated against 5-α reductase and aromatase inhibitors to study their activities as anti- hormone-dependent cancer compounds
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