Synthesis and SAR of amino acid-derived heterocyclic progesterone receptor full and partial agonists.
Two classes of amino acid-derived heterocyclic progesterone receptor ligands were developed to address the metabolic issues posed by the dimethyl amide functionality of the lead compound (1). The tetrazole-derived ligands behaved as potent partial agonists, while the 1,2,4-triazole ligands behaved as potent full agonists.
Hammond
Marlys
M
Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA. marlys.2.hammond@gsk.com
Patterson
Jaclyn R
JR
Manns
Sharada
S
Hoang
Tram H
TH
Washburn
David G
DG
Trizna
Walter
W
Glace
Lindsay
L
Grygielko
Eugene T
ET
Nagilla
Rakesh
R
Nord
Melanie
M
Fries
Harvey E
HE
Minick
Douglas J
DJ
Laping
Nicholas J
NJ
Bray
Jeffrey D
JD
Thompson
Scott K
SK
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
D000596:Amino Acids; D011980:Receptors, Progesterone; D013777:Tetrazoles