Abstract
The C3 phenylpropyl side chain of N-phenylazetidinones related to SCH 56524 was modified by replacing the hydroxymethylene with various isoelectronic or isosteric groups. Modifications at the 3' position led to less-active compounds; however, modifications at the 1' position provided compounds with improved cholesterol absorption inhibitory activity. An enantioselective route for the synthesis of C3 1'-sulfur-substituted azetidinones and the development of structure-activity relationships for this series of compounds are presented.
MeSH terms
-
Animals
-
Anticholesteremic Agents / chemical synthesis*
-
Anticholesteremic Agents / pharmacology
-
Azetidines / chemical synthesis*
-
Azetidines / chemistry
-
Azetidines / pharmacokinetics
-
Azetidines / pharmacology
-
Bile / metabolism
-
Cholesterol / metabolism
-
Intestinal Absorption / drug effects
-
Macaca fascicularis
-
Male
-
Molecular Structure
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
3-(2-phenethylsulfinyl)-4-(4-hydroxyphenyl)-N-(4-fluorophenyl)-2-azetidinone
-
3-(2-phenethylthio)-4-(4-hydroxyphenyl)-N-(4-fluorophenyl)-2-azetidinone
-
Anticholesteremic Agents
-
Azetidines
-
1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone
-
Cholesterol