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

Bioorg Med Chem Lett. 1999 Jul 5;9(13):1875-80. doi: 10.1016/s0960-894x(99)00287-5.

Abstract

A series of 3-substituted analogs 3 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 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.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*

Substances

  • Enzyme Inhibitors
  • Piperidines
  • Pyridines
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • lonafarnib