Structure and activity relationships of novel uracil derivatives as topical anti-inflammatory agents

In order to create novel, topical anti-inflammatory compounds exhibiting more potent activities than lead compound CX-659S (1), we designed and synthesized various derivatives of 1 focusing on the uracil N(1)- and N(3)-substituents, and evaluated their anti-inflammatory activities via inhibition of...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2003-11, Vol.11 (23), p.4933-4940
Main Authors: ISOBE, Yoshiaki, TOBE, Masanori, INOUE, Yoshifumi, ISOBE, Masakazu, TSUCHIYA, Masami, HAYASHI, Hideya
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Magnetic Resonance Spectroscopy
Mass Spectrometry
Medical sciences
Pharmacology. Drug treatments
Structure-Activity Relationship
Uracil - analogs & derivatives
Uracil - chemistry
Uracil - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In order to create novel, topical anti-inflammatory compounds exhibiting more potent activities than lead compound CX-659S (1), we designed and synthesized various derivatives of 1 focusing on the uracil N(1)- and N(3)-substituents, and evaluated their anti-inflammatory activities via inhibition of the picryl chloride-induced contact hypersensitivity reaction (CHR) in mice. In the course of our structure and activity relationship study, we found that compounds 6k, 6q, and 6r inhibited by approximately 50% the CHR, at 0.1 mg/ear. These activities were essentially equipotent with that of Tacrolimus, a strong immunosuppressant.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2003.09.012