title: Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives.
abstract: In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of benzofuran and benzothiophene derivatives. Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte proliferation and exerted RARalpha selectivity. One of them, 4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered significantly inhibited mouse antibody production and delayed type hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.
authors.affiliation: Tsukuba Basic Research Laboratories for Drug Discovery, Eisai Company, Ltd., Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshimura
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Hibi
authors.forename: K
authors.initials: K
authors.lastname: Tagami
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: A
authors.initials: A
authors.lastname: Ishibahi
authors.forename: K
authors.initials: K
authors.lastname: Tai
authors.forename: T
authors.initials: T
authors.lastname: Hida
authors.forename: N
authors.initials: N
authors.lastname: Tokuhara
authors.forename: M
authors.initials: M
authors.lastname: Nagai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004926:Escherichia coli; D005260:Female; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D000072482:Retinoic Acid Receptor alpha; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011758:Pyrroles; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C406083:ER 38925