Title of article :
Analogues of 1-(3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase Original Research Article
Author/Authors :
Adriano Afonso، نويسنده , , Jay Weinstein، نويسنده , , Joseph Kelly، نويسنده , , Ronald Wolin، نويسنده , , Stuart B. Rosenblum، نويسنده , , Michael Connolly، نويسنده , , Timothy Guzi، نويسنده , , Linda James-Myers، نويسنده , , Donna Carr، نويسنده , , Robert Patton Leland، نويسنده , , W.Robert Bishop، نويسنده , , Paul Kirshmeier، نويسنده , , M. Liu، نويسنده , , L. Heimark، نويسنده , , K.J. Chen، نويسنده , , A.A. Nomeir، نويسنده ,
Abstract :
The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)piperazine/piperidine is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues . The 11R(−) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.
