Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors

Duane A Burnett; Mary Ann Caplen; Martin S Domalski; Margaret E Browne; Harry R Davis Jr; John W Clader

doi:10.1016/s0960-894x(01)00750-8

Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors

Bioorg Med Chem Lett. 2002 Feb 11;12(3):311-4. doi: 10.1016/s0960-894x(01)00750-8.

Authors

Duane A Burnett¹, Mary Ann Caplen, Martin S Domalski, Margaret E Browne, Harry R Davis Jr, John W Clader

Affiliation

¹ Schering-Plough Research Institute, 2015 Galloping Hill Road MS 2800, Kenilworth, NJ 07033-0539, USA. [email protected]

PMID: 11814785
DOI: 10.1016/s0960-894x(01)00750-8

Abstract

The discoveries of Sch 48461 and Sch 58235 and their novel pharmacology of inhibition of cholesterol absorption have prompted efforts to determine their biological mechanism of action (MOA). To this end, a series of radioiodinated analogues with good to excellent in vivo activity have been designed and synthesized as single enantiomers. They are structurally consistent with the allowable SAR of the 2-azetidinone class of cholesterol absorption inhibitors.

MeSH terms

Animals
Anticholesteremic Agents / chemical synthesis*
Anticholesteremic Agents / pharmacology*
Azetidines / chemical synthesis*
Azetidines / chemistry
Azetidines / pharmacology*
Cholesterol / pharmacokinetics*
Cricetinae
Drug Design
Ezetimibe
Intestinal Absorption / drug effects*
Isotope Labeling
Stereoisomerism
Structure-Activity Relationship

Substances

2-azetidinone
Anticholesteremic Agents
Azetidines
1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone
Cholesterol
Ezetimibe