Analogs of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H- benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N- oxide as inhibitors of farnesyl protein transferase

Article abstract of DOI:10.1016/S0960-894X(99)00287-5

A series of 3-substituted analogs 3 of 4-(3-bromo-8-methyl-10-methoxy- 6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2b]pyridin-11-yl)-1-(4- pyridinylacetyl)piperidine N-oxide 2 was prepared and evaluated as FPT inhibitors. The objective of this study was to identify other substituents at C₃ in this series of FPT inhibitors that would have the FPT potency enhancement similar to that found for a C₃ bromo substituent. The 3-methyl analog 17b was found to be tenfold less active than 2, and other C₃ substituents having more steric bulk were found to cause a further reduction in activity.