Design and synthesis of fluorinated RXR modulators.
Fluorinated trienoic acid analogues of the RXR selective modulator 1 (LG101506) were synthesized, and tested for their ability to bind RXRalpha and activate RXR homo and heterodimers. Potency and efficacy were observed to be dependent upon the position of fluorination, and improvement in pharmacological profile was demonstrated in some cases.
Gernert
D L
DL
Discovery Chemistry Research, Lilly Research Laboratories, Indianapolis, IN, USA. dgernert@lilly.com
Ajamie
R
R
Ardecky
R A
RA
Bell
M G
MG
Leibowitz
M D
MD
Mais
D A
DA
Mapes
C M
CM
Michellys
P Y
PY
Rungta
D
D
Reifel-Miller
A
A
Tyhonas
J S
JS
Yumibe
N
N
Grese
T A
TA
D000818:Animals; D015195:Drug Design; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology
D017611:Fluorine Compounds; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014212:Tretinoin