Optimization of sulfonamide derivatives as highly selective EP1 receptor antagonists
| Autor: | Toshiaki Matsui, Masaki Ima, Hiroshi Yamamoto, Masaaki Toda, Hiroki Okada, Koji Yoshida, Shingo Yamamoto, Hiroshi Tsuruta, Atsushi Naganawa, Takayuki Maruyama, Kigen Kondo, Hisao Nakai |
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| Rok vydání: | 2006 |
| Předmět: |
Stereochemistry
medicine.drug_class Clinical Biochemistry Pharmaceutical Science Benzoates Biochemistry Isozyme Chemical synthesis Structure-Activity Relationship Drug Discovery medicine Cytochrome P-450 Enzyme Inhibitors Humans Receptors Prostaglandin E Receptor Molecular Biology Sulfonyl chemistry.chemical_classification Sulfonamides Chemistry Organic Chemistry Antagonist Receptor antagonist Receptors Prostaglandin E EP1 Subtype Affinities Sulfonamide Liver Molecular Medicine Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry. 14:7774-7789 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2006.08.001 |
| Popis: | A series of 4-[(2-{isobutyl[(5-methyl-2-furyl)sulfonyl]amino}phenoxy)methyl]benzoic acids and 4-({2-[isobutyl(1,3-thiazol-2-ylsulfonyl)amino]phenoxy}methyl)benzoic acids were synthesized and evaluated for their EP receptor affinities and EP1 receptor antagonist activities. Further structural optimization was carried out to reduce inhibitory activity against hepatic cytochrome P450 isozymes, which could represent a harmful potential drug interaction. Selected compounds were also evaluated for their binding affinities to hTP, hDP, mFP, and hIP, and for their hEP1 receptor antagonist activities. The results of structure-activity relationship studies are also presented. |
| Databáze: | OpenAIRE |
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