Solid-phase parallel synthesis of azarene pyrrolidinones as factor Xa inhibitors.
A focused library (4 x 14) prepared from 4-aminopyridine and 4-, 5-, and 6-azoindole templates was synthesized using 14 polymer supported 4-amido-2,3,5,6-tetrafluorophenyl (TFP) sulfonate esters inputs. Several compounds were identified as factor Xa inhibitors (IC50< or =0.1 microM) helping to establish the SAR among these four series of azarene pyrrolidinones.
Gong
Y
Y
Department of Medicinal Chemistry, Rhone-Poulenc Rorer, Collegeville, PA 19426, USA.
Becker
M
M
Choi-Sledeski
Y M
YM
Davis
R S
RS
Salvino
J M
JM
Chu
V
V
Brown
K D
KD
Pauls
H W
HW
D000925:Anticoagulants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones