An enzymatic synthesis of glucuronides of azetidinone-based cholesterol absorption inhibitors.
Two derivatives, 1 and 3, of a novel cholesterol absorption inhibitor, Sch 58235, were glucuronidated with the help of glucuronyl transferases derived from bovine and dog liver microsomes. An efficient procedure for the iodination of 4 was developed on an analytical scale to be used for the preparation of a 125I-labeled radioactive glucuronide 5.
Reiss
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P
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Burnett
D A
DA
Zaks
A
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry*; D001384:Azetidines / Q000737:chemistry*; D002417:Cattle; D002784:Cholesterol / Q000493:pharmacokinetics; D004285:Dogs; D000069438:Ezetimibe; D005965:Glucuronates / Q000138:chemical synthesis* / Q000737:chemistry*; D020719:Glucuronides / Q000138:chemical synthesis*; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000378:metabolism*; D000882:Haplorhini; D007413:Intestinal Mucosa / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008623:Mercaptoethanol / Q000737:chemistry; D008862:Microsomes, Liver / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D011817:Rabbits; D051381:Rats; D013830:Thiadiazoles / Q000737:chemistry*; D014535:Uridine Diphosphate Glucuronic Acid / Q000737:chemistry / Q000378:metabolism
C401944:1-O-(4-(1-(2,1,3-benzothiadiazol-4-yl)-3-(3-hydroxy-3-(4-fluorophenyl)propyl)-2-oxo-4-azetidinyl)phenyl)glucuronic acid; C401945:1-O-(4-(1-(4-benzoylphenyl)-3-(3-hydroxy-3-(4-tributylstannylphenyl)propyl)-2-oxo-4-azetidinyl)phenyl)glucuronic acid; C401946:1-O-(4-(1-(4-benzoylphenyl)-3--(3-hydroxy-3-(4-iodophenyl)propyl)-2-oxo-4-azetidinyl)phenyl)glucuronic acid; C116379:2-azetidinone; D000924:Anticholesteremic Agents; D001384:Azetidines; D005965:Glucuronates; D020719:Glucuronides; D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; D013830:Thiadiazoles; D014535:Uridine Diphosphate Glucuronic Acid; D008623:Mercaptoethanol; D002784:Cholesterol; D014453:Glucuronosyltransferase; D000069438:Ezetimibe