Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency.

Abstract

Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered bioavailable aryl tetrahydropyridines that are potent in cell culture. The design, synthesis, SAR and biological properties of these compounds will be discussed.

• Authors: Stephen L Gwaltney 2nd, Stephen J O'Connor, Lissa T J Nelson, Gerard M Sullivan, Hovis Imade, Weibo Wang, Lisa Hasvold, Qun Li, Jerome Cohen, Wen-Zhen Gu, Stephen K Tahir, Joy Bauch, Kennan Marsh, Shi-Chung Ng, David J Frost, Haiying Zhang, Steve Muchmore, Clarissa G Jakob, Vincent Stoll, Charles Hutchins, Saul H Rosenberg, Hing L Sham
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 13 Issue 7 Pg. 1363-6 (Apr 07 2003) ISSN: 0960-894X [Print] England
• PMID: 12657283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Enzyme Inhibitors
• Pyridines
• Alkyl and Aryl Transferases
• Farnesyltranstransferase

Topics

• Alkyl and Aryl Transferases (antagonists & inhibitors)
• Alkylation
• Animals
• Biological Availability
• Dogs
• Enzyme Inhibitors (chemical synthesis, pharmacokinetics, pharmacology)
• Farnesyltranstransferase
• Half-Life
• Models, Molecular
• Pyridines (chemical synthesis, pharmacokinetics, pharmacology)
• Structure-Activity Relationship