ABSTRACT
2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.
Subject(s)
Antiviral Agents/chemistry , Cysteine Endopeptidases , Neuraminidase/antagonists & inhibitors , Pyrimidines/chemistry , Viral Proteins/antagonists & inhibitors , Antiviral Agents/chemical synthesis , Coronavirus 3C Proteases , Cysteine Endopeptidases/chemistry , Influenza A Virus, H3N2 Subtype/enzymology , Neuraminidase/chemistry , Pyrimidines/chemical synthesis , Structure-Activity Relationship , Viral Proteins/chemistryABSTRACT
Base catalyzed condensation of enaminoketones (3a,b) with malononitrile yields the respective 7-imino-5[2(substituted)prop-1-enyl]furochromene-6-carbonitriles (4a-d) according to the nature of base used. Compounds (3a, b) condense also with indan-1,3-diketone (5) to give α, ß-unsaturated carbonyl compounds (6a) and (6b), respectively. Pyrrolidine-catalyzed condensation of visnaginone (2a) and khellinone (2b) with active methylenes yields the corresponding 1-[7,7-(substituted) furobenzodihydropyrone derivatives (7a-e) which condense with semicarbazide to give the respective semicarbazones (8a-e). Compounds (8b,e) react with thionyl chloride to give the respective 1,2,3-thiadiazoles (9a,b) meanwhile compounds (8a-e) react also with selenium dioxide to give 1,2,3-selenadiazoles (9c-g), respectively. Chalcones (11a,b) were obtained upon condensing (2a,b) with ferrocene-2-carboxaldehyde (10). Compatible elementary and spectroscopic measurements were in good accord with the structures postulated for the new compounds. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of four (breast: MCF-7, cervix: HELA, colon: HCT116 and liver: HEPG2) human solid tumor cell lines and the structure activity relationship (SAR) was discussed.