Discovery of potent imidazole and cyanophenyl containing farnesyltransferase inhibitors with improved oral bioavailability

Yunsong Tong; Nan-Horng Lin; Le Wang; Lisa Hasvold; Weibo Wang; Nicholas Leonard; Tongmei Li; Qun Li; Jerry Cohen; Wen-Zhen Gu; Haiying Zhang; Vincent Stoll; Joy Bauch; Kennan Marsh; Saul H Rosenberg; Hing L Sham

doi:10.1016/s0960-894x(03)00195-1

Discovery of potent imidazole and cyanophenyl containing farnesyltransferase inhibitors with improved oral bioavailability

Bioorg Med Chem Lett. 2003 May 5;13(9):1571-4. doi: 10.1016/s0960-894x(03)00195-1.

Authors

Yunsong Tong¹, Nan-Horng Lin, Le Wang, Lisa Hasvold, Weibo Wang, Nicholas Leonard, Tongmei Li, Qun Li, Jerry Cohen, Wen-Zhen Gu, Haiying Zhang, Vincent Stoll, Joy Bauch, Kennan Marsh, Saul H Rosenberg, Hing L Sham

Affiliation

¹ R47B, AP10, Global Pharmaceutical R&D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. [email protected]

PMID: 12699757
DOI: 10.1016/s0960-894x(03)00195-1

Abstract

A pyridyl moiety was introduced into a previously developed series of farnesyltransferase inhibitors containing imidazole and cyanophenyl (such as 4), resulting in potent inhibitors with improved pharmacokinetics.

Publication types

Comparative Study
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Administration, Oral
Alkyl and Aryl Transferases / antagonists & inhibitors*
Animals
Biological Availability
Crystallography, X-Ray
Dogs
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Farnesyltranstransferase
Haplorhini
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
Models, Molecular
Nitriles / chemical synthesis*
Nitriles / chemistry
Nitriles / pharmacology
Stereoisomerism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Imidazoles
Nitriles
Alkyl and Aryl Transferases
Farnesyltranstransferase