Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives.
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.
Yoshimura
H
H
Tsukuba Basic Research Laboratories for Drug Discovery, Eisai Company, Ltd., Ibaraki, Japan.
Kikuchi
K
K
Hibi
S
S
Tagami
K
K
Satoh
T
T
Yamauchi
T
T
Ishibahi
A
A
Tai
K
K
Hida
T
T
Tokuhara
N
N
Nagai
M
M
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
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