Highly potent naphthofuran-based retinoic acid receptor agonists.
A collection of arotinoids with a central benzofuran or naphthofuran ring structure was efficiently synthesized by a three-step process that comprises a Sonogashira coupling, an iodine-induced 5-endo-dig cyclization of the o-methoxyphenyl- or naphthyl-ethynyl benzoates, and finally a Suzuki/Sonogashira coupling of the corresponding 3-iodobenzo- or naphthofurans. Most of these 3-substituted naphthofuran arotinoids (but not the 5,7-di-tert-butylbenzofurans with the same substitution pattern at the C2 and C3 positions) are potent agonists of the retinoic acid receptor (RAR) subtypes, with activities in the nanomolar range.
Departamento de Química Orgánica, Universidade de Vigo, Lagoas-Marcosende, 36310 Vigo, Spain.
Efrén Pérez
EP
Santín
Harshal
H
Khanwalkar
Johannes
J
Voegel
Pascal
P
Collette
Pascale
P
Mauvais
Hinrich
H
Gronemeyer
Angel R
AR
de Lera
D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D001572:Benzofurans; D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid; C105430:benzofuran