Synthesis, Biological, and Structural Explorations of New Zwitterionic Derivatives of 14- O-Methyloxymorphone, as Potent μ/δ Opioid Agonists and Peripherally Selective Antinociceptives.

Herein, the synthesis and pharmacological characterization of an extended library of differently substituted N-methyl-14- O-methylmorphinans with natural and unnatural amino acids and three dipeptides at position 6 that emerged as potent μ/δ opioid receptor (MOR/DOR) agonists with peripheral antinociceptive efficacy is reported. The current study adds significant value to our initial structure-activity relationships on a series of zwitterionic analogues of 1 (14- O-methyloxymorphone) by targeting additional amino acid residues. The new derivatives showed high binding and potent agonism at MOR and DOR in vitro.

Comparative in vitro anti-hepatitis C virus activities of a selected series of polymerase, protease, and helicase inhibitors.

We report here a comparative study of the anti-hepatitis C virus (HCV) activities of selected (i) nucleoside polymerase, (ii) nonnucleoside polymerase, (iii) alpha,gamma-diketo acid polymerase, (iv) NS3 protease, and (v) helicase inhibitors, as well as (vi) cyclophilin binding molecules and (vii) alpha 2b interferon in four different HCV genotype 1b replicon systems.

The imidazopyrrolopyridine analogue AG110 is a novel, highly selective inhibitor of pestiviruses that targets the viral RNA-dependent RNA polymerase at a hot spot for inhibition of viral replication.

Ethyl 2-methylimidazo[1,2-a]pyrrolo[2,3-c]pyridin-8-carboxylate (AG110) was identified as a potent inhibitor of pestivirus replication. The 50% effective concentration values for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect, viral RNA synthesis, and production of infectious virus were 1.2 +/- 0.