Anti‐HAV Activity of Some Newly Synthesized Triazolo[4,3‐b]pyridazines

Abstract

6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazine-3(2H)-thione 2 was used as precursor for the preparation of some novel 3-S-substituted-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazine derivatives 3-11. Furthermore, the preparation of 1-[2-(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-acetyl]-1H-pyrazole derivative 13 and 5-(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanylmethyl)-[1,3,4]oxadiazole derivatives 15 and 17, are described. Some of the prepared products revealed a promising antiviral activity against hepatitis-A virus (HAV, MBB-cell culture adapted strain). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with the test compounds. Compound 15 showed the highest effect on HAV compared to the other tested compounds.

Facile Synthesis of New [1,2,4]Triazolo[4,3‐b]pyridazine

“…It is notable that the displacement of chemical shift for 2H (H-2,6) of the phenylhydrazone moiety to downfield can be attributed to anisotropic effect of the triazolo ring. The reaction of 5a-c with carbon disulfide in dry pyridine [13] yielded the corresponding thiones 9a-c (Scheme 4). The IR spectra showed absorption bands assignable to the (NH) and (C=S) groups along with their 1 H nmr spectra, which revealed a signal at aromatic region for the NH proton (D 2 O exchangeable).…”

“…Finally, The S-alkylated compounds 10a-o were prepared by reacting thiones 9a-c with appropriate alkyl halides in the presence of sodium hydroxide [13] (Scheme 4).…”

“…The reaction of 5a , 5b , 5c with carbon disulfide in dry pyridine yielded the corresponding thiones 9a , 9b , 9c (Scheme ). The IR spectra showed absorption bands assignable to the (NH) and (C=S) groups along with their 1 H nmr spectra, which revealed a signal at aromatic region for the NH proton (D 2 O exchangeable).…”

“…In the last decades, the chemistry of triazolo[4,3‐ b ]pyridazine derivatives has received considerable attention owing to their varied biological activities, such as antiviral , antitumor , sedative/hypnotic , anti‐anxiety , adenine receptor ligand , hypotensive, herbicidal, pesticidal , bactericidal and anti‐HAV activity . In the light of these information and due to our continuing interest in the synthesis of biologically important heterocycles in this paper, we wish to report the facile syntheses of some new derivatives of triazolo[4,3‐ b ]pyridazines.…”

The Medicinal Chemistry of Antihepatitis Agents I

“…Because of these specificities, mostly peptide-based compounds were studied as HAV 3Cpro inhibitors. However, so far, the following different types of 3Cpro inhibitors have been studied: a. peptide aldehyde inhibitors b. azaglutamine and keto-glutamine derivatives (Huang et al, 1999;Ramtohul et al, 2002a) c. azodicarboxamides (Hill and Vederas, 1999) d. pseudoxazolones (Ramtohul et al, 2002b) e. serine and threonine b-lactones (Lall et al, 1999(Lall et al, , 2002 f. triazolo [4,3-b]pyridazines (Shamroukh and Ali, 2008) g. heteroaromatic esters (Huitema et al, 2008)…”