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.
Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA. marlys.2.hammond@gsk.com
Marlys
M
Hammond
Jaclyn R
JR
Patterson
Sharada
S
Manns
Tram H
TH
Hoang
David G
DG
Washburn
Walter
W
Trizna
Lindsay
L
Glace
Eugene T
ET
Grygielko
Rakesh
R
Nagilla
Melanie
M
Nord
Harvey E
HE
Fries
Douglas J
DJ
Minick
Nicholas J
NJ
Laping
Jeffrey D
JD
Bray
Scott K
SK
Thompson
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