Syntheses and evaluation of naphthalenyl- and chromenyl-pyrrolyl-benzoic acids as potent and selective retinoic acid receptor alpha agonists.
Synthesis and structure activity relationships (SAR) of RAR alpha-selective agonists are discussed. 4-[5-(5,8-Dimethyl-2H-3-chromenyl)-1H-2-pyrrolyl]benzoic acid (12a), which possesses a flat structural moiety and an oxygen atom at the hydrophobic part, showed highly selective transactivation activity at the RAR alpha receptor.
Hibi
S
S
Tsukuba Basic Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. s-hibi@hhc.eisai.co.jp
Tagami
K
K
Kikuchi
K
K
Yoshimura
H
H
Tai
K
K
Hida
T
T
Tokuhara
N
N
Yamauchi
T
T
Nagai
M
M
D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D000072482:Retinoic Acid Receptor alpha; D013329:Structure-Activity Relationship
D001565:Benzoates; D001578:Benzopyrans; D009281:Naphthalenes; D011758:Pyrroles; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha