Novel retinoidal tropolone derivatives. Bioisosteric relationship of tropolone ring with benzoic acid moiety in retinoid structure.
Several tropolone derivatives (4-7) were designed as novel retinoids on the assumption that the tropolone ring may mimic the benzoic acid moiety in retinoid structures, such as Am80 (2). Among the synthesized compounds, 5-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethynyl]tropolone (7a) showed moderate potency as a differentiation-inducer of HL-60 cells. The activities of the tropolones were greatly enhanced in the presence of HX630, an RXR agonist (retinoid synergist).
Ebisawa
M
M
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Ohta
K
K
Kawachi
E
E
Fukasawa
H
H
Hashimoto
Y
Y
Kagechika
H
H
D001565:Benzoates / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D007536:Isomerism; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D047488:Retinoid X Receptors; D012176:Retinoids / Q000737:chemistry*; D014157:Transcription Factors / Q000187:drug effects; D014334:Tropolone / Q000737:chemistry*
D001565:Benzoates; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014334:Tropolone