Multiple strategies for the preparation of a sulfur-35 labeled NPC1L1 radioligand.
During our effort to design a receptor binding assay to aid in the elucidation of the molecular mechanism of ezetimibe, we prepared a sulfur-35 containing radioligand which exhibits improved potency over the glucuronide conjugate of ezetimibe in both native enterocyte brush border membranes and membranes from cells expressing recombinant NPC1L1. Herein, we describe the different synthetic strategies which were used to obtain this compound as well as its effectiveness in the aforementioned assay.
Simeone
Joseph P
JP
Department of Process Research, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. joe_simeone@merck.com
Braun
Matthew P
MP
Leone
Joseph F
JF
Lin
Peter
P
DeVita
Robert J
RJ
Garcia-Calvo
Margarita
M
Bull
Herb G
HG
Lisnock
JeanMarie
J
Dean
Dennis C
DC
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D000069438:Ezetimibe; D020719:Glucuronides / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000737:chemistry
D000924:Anticholesteremic Agents; D001384:Azetidines; D020719:Glucuronides; D008024:Ligands; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D000069438:Ezetimibe