Amides of piperidine, morpholine and piperazine substituted 1-phenylethylamines: inhibitors of acylCoA:cholesterol acyltransferase (ACAT) activity in vitro and in vivo.
Amides of some substituted 1,2-diarylethylamines have been shown to exhibit potent acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) inhibitory activity in vitro in microsomal ACAT assays but show poor in vivo activity in a cholesterol-fed hamster model. In an effort to design ACAT inhibitors that are potent in both our in vitro and in vivo assays a series of amides of piperidine, morpholine and piperazine substituted 1-phenylethylamines were synthesized. Compounds of this series were found to be very potent inhibitors of ACAT in a microsomal ACAT assay and also exhibited potent activity in a cholesterol-fed hamster model.
Dugar
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S
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Davis
H R
HR
Burrier
R E
RE
Salisbury
B G
BG
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010627:Phenethylamines / Q000138:chemical synthesis / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D009025:Morpholines; D010627:Phenethylamines; D010879:Piperazines; D010880:Piperidines; D002785:Sterol O-Acyltransferase