Design and synthesis of benzofused heterocyclic RXR modulators.
Benzofused heterocyclic analogs 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 choice of heterocycle as well as the sidechain employed.
Gernert
D L
DL
Discovery Chemistry Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA. dgernert@lilly.com
Neel
D A
DA
Boehm
M F
MF
Leibowitz
M D
MD
Mais
D A
DA
Michellys
P Y
PY
Rungta
D
D
Reifel-Miller
A
A
Grese
T A
TA
D000818:Animals; D001554:Benzene / Q000737:chemistry; D002460:Cell Line; D002522:Chlorocebus aethiops; D015195:Drug Design; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D047495:PPAR gamma; D011485:Protein Binding; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry; D047491:Retinoid X Receptor gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
D006575:Heterocyclic Compounds, 3-Ring; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha; D047491:Retinoid X Receptor gamma; D047488:Retinoid X Receptors; D001554:Benzene