ABSTRACT
We successfully discovered peptidomimetic motilin antagonists (17c and 17d) through the improvement of physicochemical properties of a tetrapeptide antagonist (2). Furthermore, with oral administration and based on motilin antagonistic activity, both compounds suppressed motilin-induced colonic and gastric motility in conscious dogs.
Subject(s)
Gastrointestinal Agents/antagonists & inhibitors , Motilin/antagonists & inhibitors , Oligopeptides/chemical synthesis , Peptides/chemistry , Animals , Caco-2 Cells , Cell Line , Drug Discovery , Gastrointestinal Agents/metabolism , Humans , Motilin/metabolism , Oligopeptides/chemistry , Oligopeptides/pharmacology , Peptides/chemical synthesis , Permeability , Rabbits , RatsABSTRACT
Nitrosation of 3-methoxyphenol and 1-naphthol were examined under both acidic (NaNO(2)-EtCO(2)H-H(2)O) and basic (i-AmNO(2)-K(2)CO(3)-DMF) conditions. Acidic nitrosations afforded ortho-directed products, whereas para-directed nitrosations were observed under basic conditions to yield p-quinone monooximes. The basic para-directed nitrosation was further examined using 15 phenols, two naphthols, and four phenolic heterocyclics. A one-pot operation of the basic nitrosation followed by methylation with dimethyl sulfate gave the corresponding methyl ethers in high yield. Two p-quinone monooximes derived from 3-methoxyphenol and 8-hydroxyquinoline showed a moderate activity against HSV-1, and the latter oxime was also effective against HSV-2. On the other hand, p-quinone monooximes derived from methyl salicylate, 1-naphthol, 7-hydroxy-2-methylbenzo[b]furan, and 8-hydroxycoumarin showed the comparable activity to that of DDI against HIV-1.
