Trisubstituted benzene leukotriene B4 receptor antagonists: Synthesis and structure-activity relationships
| Autor: | Takahiko Nakae, Nobuyuki Hamanaka, Yoshihiko Odagaki, Hisao Nakai, Shigeru Sakuyama, Mitoshi Konno |
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| Rok vydání: | 1997 |
| Předmět: |
Agonist
Neutrophils medicine.drug_class Stereochemistry Clinical Biochemistry Receptors Leukotriene B4 Pharmaceutical Science Leukotriene B4 Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Benzene Derivatives medicine Humans Receptor Benzene Molecular Biology Cell Aggregation Aryl Organic Chemistry Leukotriene B4 receptor Receptor antagonist chemistry Leukotriene B Molecular Medicine Lead compound |
| Zdroj: | Bioorganic & Medicinal Chemistry. 5:1649-1674 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(97)00089-8 |
| Popis: | A series of trisubstituted benzenes which demonstrate leukotriene B 4 (LTB 4 , 1 ) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB 4 receptor but demonstrated agonist activity in functional assays. Compound 3a , the initial lead compound of this new series, showed only modest affinity (IC 50 = 0.20 μM). However, 3a was a receptor antagonist with no demonstrable agonist activity up to 30 μM. 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 LTB 4 receptor ( K i = 3.7±0.9 nM). |
| Databáze: | OpenAIRE |
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