Trisubstituted benzene leukotriene B4 receptor antagonists: synthesis and structure-activity relationships

A series of trisubstituted benzenes which demonstrate leukotriene B4 (LTB4, 1) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB4 receptor but demonstrated agonist activity in functional assays. Compound 3a, the initial lead compound...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1997-08, Vol.5 (8), p.1649
Main Authors: Konno, M, Nakae, T, Sakuyama, S, Odagaki, Y, Nakai, H, Hamanaka, N
Format: Article
Language:English
Subjects:
Benzene Derivatives - chemistry
Benzene Derivatives - pharmacology
Cell Aggregation - drug effects
Humans
Leukotriene B4 - metabolism
Neutrophils - cytology
Neutrophils - metabolism
Receptors, Leukotriene B4 - antagonists & inhibitors
Receptors, Leukotriene B4 - chemistry
Structure-Activity Relationship
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of trisubstituted benzenes which demonstrate leukotriene B4 (LTB4, 1) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB4 receptor but demonstrated agonist activity in functional assays. Compound 3a, the initial lead compound of this new series, showed only modest affinity (IC50 = 0.20 microM). However, 3a was a receptor antagonist with no demonstrable agonist activity up to 30 microM. Further modification of the lipid tail and aryl head groups region led to the discovery of 3b (ONO-4057). This compound, free of agonist activity, possesses high affinity to the LTB4 receptor (Ki = 3.7 +/- 0.9 nM).
ISSN:0968-0896
DOI:10.1016/S0968-0896(97)00089-8