Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors.
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.
Burnett
Duane A
DA
Schering-Plough Research Institute, 2015 Galloping Hill Road MS 2800, Kenilworth, NJ 07033-0539, USA. duane.burnett@spcorp.com
Caplen
Mary Ann
MA
Domalski
Martin S
MS
Browne
Margaret E
ME
Davis
Harry R
HR
Clader
John W
JW
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000493:pharmacokinetics*; D006224:Cricetinae; D015195:Drug Design; D000069438:Ezetimibe; D007408:Intestinal Absorption / Q000187:drug effects*; D007553:Isotope Labeling; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C116379:2-azetidinone; D000924:Anticholesteremic Agents; D001384:Azetidines; C095487:1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone; D002784:Cholesterol; D000069438:Ezetimibe