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

Bioorganic & Medicinal Chemistry Letters
1999.0

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.

Knowledge Graph

Similar Paper

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
Bioorganic & Medicinal Chemistry Letters 1999.0
(+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide (SCH-66336):  A Very Potent Farnesyl Protein Transferase Inhibitor as a Novel Antitumor Agent
Journal of Medicinal Chemistry 1998.0
Exploring the Role of Bromine at C(10) of (+)-4-[2-[4-(8-Chloro-3,10-dibromo- 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2- oxoethyl]-1-piperidinecarboxamide (Sch-66336):  The Discovery of Indolocycloheptapyridine Inhibitors of Farnesyl Protein Transferase
Journal of Medicinal Chemistry 2002.0
Bridgehead modification of trihalocycloheptabenzopyridine lead to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability
Bioorganic & Medicinal Chemistry Letters 2004.0
Identification of Pharmacokinetically Stable 3,10-Dibromo-8-chlorobenzocycloheptapyridine Farnesyl Protein Transferase Inhibitors with Potent Enzyme and Cellular Activities
Journal of Medicinal Chemistry 1999.0
Tricyclic Farnesyl Protein Transferase Inhibitors:  Crystallographic and Calorimetric Studies of Structure−Activity Relationships
Journal of Medicinal Chemistry 1999.0
Bridgehead modification of trihalocycloheptabenzopyridine lead to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability
Bioorganic & Medicinal Chemistry Letters 2004.0
Potent and Selective Farnesyl Transferase Inhibitors
Journal of Medicinal Chemistry 2004.0
Introduction of methionine mimics on 3-arylthiophene: influence on protein farnesyltransferase inhibition and on antiparasitic activity
MedChemComm 2013.0
Pepticinnamins, new farnesyl-protein transferase inhibitors produced by an actinomycete. I. Producing strain, fermentation, isolation and biological activity.
The Journal of Antibiotics 1993.0