title: Novel 1,4-diarylpiperidine-4-methylureas as anti-hyperlipidemic agents: dual effectors on acyl-CoA:cholesterol O-acyltransferase and low-density lipoprotein receptor expression.
abstract: A family of 1,4-diarylpiperidine-4-methylureas were designed and synthesized as novel dual effectors on ACAT and LDL receptor expression. We examined SAR of the synthesized compounds focusing on substitution at the three aromatic parts of the starting compound 1 and succeeded in identifying essential substituents for inhibition of ACAT and up-regulation of hepatic LDL receptor expression. Especially, we found that compound 12f, which can easily be prepared, has biological properties comparable to those of SMP-797, a promising ACAT inhibitor. In addition, the in vitro effects of 12f on lipid metabolism were substantially superior to those of a known ACAT inhibitor, Avasimibe.
authors.affiliation: Research Division, Dainippon Sumitomo Pharma Co., Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan. shigehiro-asano@ds-pharma.co.jp
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Asano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ban
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kino
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ioriya
authors.forename: Masami
authors.initials: M
authors.lastname: Muraoka
mesh_terms: D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008782:Methylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008782:Methylurea Compounds; D009287:Naphthyridines; D010880:Piperidines; D011973:Receptors, LDL; C508738:SMP-797; D002785:Sterol O-Acyltransferase