Synthesis of 5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidine-N-cyanoguanidine derivatives as inhibitors of ras farnesyl protein transferase

A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT) inhibitors was prepared. Replacement of a piperidine amide-group with a N-cyanoguanidine functionality increased FPT activity. X-ray crystal structure determination of 42 complexed with FPT revealed differences in the in...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-02, Vol.12 (4), p.601-605
Main Authors: Cooper, Alan B, Strickland, Corey L, Wang, James, Desai, Jagdish, Kirschmeier, Paul, Patton, Robert, Bishop, W Robert, Weber, Patricia C, Girijavallabhan, V
Format: Article
Language:English
Subjects:
Alkyl and Aryl Transferases - antagonists & inhibitors
Crystallography, X-Ray
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Guanidines - chemical synthesis
Guanidines - chemistry
Guanidines - pharmacology
Heterocyclic Compounds, 4 or More Rings - chemical synthesis
Heterocyclic Compounds, 4 or More Rings - chemistry
Heterocyclic Compounds, 4 or More Rings - pharmacology
Humans
Inhibitory Concentration 50
Molecular Structure
Piperidines - chemical synthesis
Piperidines - chemistry
Piperidines - pharmacology
Structure-Activity Relationship
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Summary:A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT) inhibitors was prepared. Replacement of a piperidine amide-group with a N-cyanoguanidine functionality increased FPT activity. X-ray crystal structure determination of 42 complexed with FPT revealed differences in the interactions of the amide and N-cyanoguanidine groups with the protein.
ISSN:0960-894X
DOI:10.1016/S0960-894X(01)00826-5