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A series of N -((1,3-diphenyl-1 H -pyrazol-4-yl)methyl)anilines were synthesized and evaluated in vitro for cytotoxicity and antiviral activity against a large panel of viruses. Most of the tested compounds interfered with RSV replication in the micromolar concentrations (EC 50 s ranging from 5 μM to 28 μM). SAR studies suggested that the presence of a trifluoromethyl group in R 1 abolished the anti-RSV activity and enhanced the cytotoxicity while the best results in term of both anti-RSV activity and selectivity were obtained by the introduction in R 1 of a chlorine or a bromine atom. [ABSTRACT FROM AUTHOR]

A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones 1a−w, 3-benzyl-4H-chromen-4-ones 2a−g, and 3-benzylchroman-4-ones 3a−e] have been synthesized and tested in vitro as inhibitors of human monoamine oxidase isoforms A and B (hMAO-A and hMAO-B). Most of the compounds were found to be potent and selective MAO-B inhibitors. In general, the (E)-3-benzylidenechroman-4-ones 1a−wshowed activities in the nano- or micromolar range coupled with high selectivity against hMAO-B. The reduction of the exocyclic double bond results in compounds 3a−eselective against isoform B and active in the micromolar range. In contrast, the endocyclic migration of the double bond (compounds 2a−g) generally produces the loss of the inhibitory activity or a marked reduction in potency. (E)-3-(4-(Dimethylamino)benzylidene)chroman-4-one (1l) and (E)-5,7-dihydroxy-3-(4-hydroxybenzylidene)chroman-4-one (1h) were the most interesting compounds of the entire series of inhibitors, showing hMAO-B affinity better than the selective inhibitor selegiline. Molecular modeling studies have been carried out to explain the selectivity of the most active homoisoflavonoids 1hand 1l. [ABSTRACT FROM AUTHOR]

Abstract: A series of 3-benzyl chromenes and chromans were synthesized and tested in vitro against human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. All the new compounds, with the exception of 3-benzyl-2H-chromene (3a), showed a potent activity against HRV serotype 1B within micro or submicromolar range (IC50s from 0.11 to 6.62μM). The low cytotoxicity of all the derivatives resulted in compounds with high therapeutic index (TI). On the contrary, HRV 14 infection was only weakly inhibited by the majority of these compounds. The 3-benzylidenechromans 2b and 2c showed the highest anti-HRV 1B activity (IC50 0.12 and 0.11μM, respectively) coupled with remarkable TI (625.00 and 340.91, respectively). Mechanism of action studies on (Z)-3-(4-chlorobenzylidene)chroman (2b) suggest that the new compounds behave as capsid binders and interfere with very early stages of HRV 1B replication, similarly to related flavanoids. [Copyright &y& Elsevier]

Abstract: A series of 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (3a–k and 4a–u) were designed, synthesized, and evaluated for their inhibitory efficacy towards the two hMAO isoforms. Most of the derivatives were found to be potent and selective hMAO-B inhibitors. In particular, derivative 3g showed greater hMAO-B affinity than selective inhibitor selegiline coupled with high selectivity index (SI=145). The most selective hMAO-B inhibitor was the 3-methyl analogue 3f with an SI higher than 909. [Copyright &y& Elsevier]

The synthesis of 30 title compounds of type (III) or (VI) is outlined and the compounds are screened for their inhibitory efficacy towards the two hMAO isoforms. [ABSTRACT FROM AUTHOR]