Small molecule tertiary amines as agonists of the nuclear hormone receptor Rev-erbα.
The structure-activity relationship study of a small molecule Rev-erbα agonist is reported. The potency and efficacy of the agonists in a cell-based assay were optimized as compared to the initial lead. Modest mouse pharmacokinetics coupled with an improved in vitro profile make 12e a suitable in vivo probe to interrogate the functions of Rev-erbα in animal models of disease.
Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
Youseung
Y
Shin
Romain
R
Noel
Subhashis
S
Banerjee
Douglas
D
Kojetin
Xinyi
X
Song
Yuanjun
Y
He
Li
L
Lin
Michael D
MD
Cameron
Thomas P
TP
Burris
Theodore M
TM
Kamenecka
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D000588:Amines; D001596:Benzylamines; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D013876:Thiophenes