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.
Santín
Efrén Pérez
EP
Departamento de Química Orgánica, Universidade de Vigo, Lagoas-Marcosende, 36310 Vigo, Spain.
Khanwalkar
Harshal
H
Voegel
Johannes
J
Collette
Pascal
P
Mauvais
Pascale
P
Gronemeyer
Hinrich
H
de Lera
Angel R
AR
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