Format

Send to

Choose Destination
Bioorg Med Chem. 2009 Jul 1;17(13):4636-46. doi: 10.1016/j.bmc.2009.04.059. Epub 2009 May 3.

Synthesis and structure-activity relationships of N-(4-amino-2,6-diisopropylphenyl)-N'-(1,4-diarylpiperidine-4-yl)methylureas as anti-hyperlipidemic agents.

Author information

1
Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan. shigehiro-asano@ds-pharma.co.jp

Abstract

Based on 1,4-diarylpiperidine-4-methylureas, a new class of ACAT inhibitors, we examined in the study the SAR of a series of compounds prepared by replacing the substituent at the three aromatic parts. Introduction of long alkoxy group onto the phenyl moiety at the B-part was effective in improving both the inhibitory activity for ACAT and the up-regulatory activity for LDL-R expression. Particularly, 3-hydroxypropoxy group (43) on the phenyl moiety of B-part led to improved solubility, while keeping both biological activities. Compound 43 inhibited ACAT activity with an IC(50) value of 18 nM, which is superior to that of a known ACAT inhibitor, CI-1011. In addition, compound 43 revealed an LDL-R up-regulatory activity comparable to that of SMP-797. We therefore expect this compound to be a novel ACAT inhibitor.

PMID:
19464189
DOI:
10.1016/j.bmc.2009.04.059
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center