Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications

Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.     

Dopaminergic activity of some apomorphine analogs

The dopaminergic activity of ten apomorphine analogs was studied in rats lesioned unilaterally with 6-hydroxydopamine in the nigro-striatal system. Of these ten compounds, N,N-dimethyl-5,6-dihydroxy-2-amino-tetralin (M-7), N-methyl-5,6-dihydroxy-2-aminotetralin (M-8) and N,N-dimethyl-4,5-dihydroxy-2-aminoindan (DDAI) exhibited potent dopaminergic stimulant activity by causing the rat to turn to the unoperated side. The turning behavior of apomorphine, M-7, DDAI and d-amphetamine were antagonized by haloperidol. M-7 and DDAI also induced pecking in pigeons and their effects were also blocked by haloperidol. It is concluded that M-7, M-8 and DDAI are direct acting central dopaminergic agents.