Pyridone-containing farnesyltransferase inhibitors: synthesis and biological evaluation

Lisa A Hasvold; Weibo Wang; Stephen L Gwaltney 2nd; Todd W Rockway; Lissa T J Nelson; Robert A Mantei; Stephen A Fakhoury; Gerard M Sullivan; Qun Li; Nan-Horng Lin; Le Wang; Haiying Zhang; Jerome Cohen; Wen-Zhen Gu; Kennan Marsh; Joy Bauch; Saul Rosenberg; Hing L Sham

doi:10.1016/j.bmcl.2003.08.058

Pyridone-containing farnesyltransferase inhibitors: synthesis and biological evaluation

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4001-5. doi: 10.1016/j.bmcl.2003.08.058.

Authors

Lisa A Hasvold¹, Weibo Wang, Stephen L Gwaltney 2nd, Todd W Rockway, Lissa T J Nelson, Robert A Mantei, Stephen A Fakhoury, Gerard M Sullivan, Qun Li, Nan-Horng Lin, Le Wang, Haiying Zhang, Jerome Cohen, Wen-Zhen Gu, Kennan Marsh, Joy Bauch, Saul Rosenberg, Hing L Sham

Affiliation

¹ Pharmaceutical Discovery, R-47B, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. lisa.hasvold@abbott.com

PMID: 14592494
DOI: 10.1016/j.bmcl.2003.08.058

Abstract

Farnesyltransferase inhibitors (FTIs) have been developed as potential anti-cancer agents due to their efficacy in blocking malignant growth in a variety of murine models of human tumors. To that end, we have developed a series of pyridone farnesyltransferase inhibitors with potent in vitro and cellular activity. The synthesis, SAR and biological properties of these compounds will be discussed.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / toxicity
Cell Division / drug effects
Cell Line, Tumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / toxicity
Farnesyltranstransferase
Humans
Molecular Structure
Pyridones / chemical synthesis*
Pyridones / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Enzyme Inhibitors
Pyridones
Alkyl and Aryl Transferases
Farnesyltranstransferase