Anthranilamide inhibitors of factor Xa.
SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.
Mendel
David
D
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. mendel_david@lilly.com
Marquart
Angela L
AL
Joseph
Sajan
S
Waid
Philip
P
Yee
Ying K
YK
Tebbe
Anne Louise
AL
Ratz
Andrew M
AM
Herron
David K
DK
Goodson
Theodore
T
Masters
John J
JJ
Franciskovich
Jeffry B
JB
Tinsley
Jennifer M
JM
Wiley
Michael R
MR
Weir
Leonard C
LC
Kyle
Jeffrey A
JA
Klimkowski
Valentine J
VJ
Smith
Gerald F
GF
Towner
Richard D
RD
Froelich
Larry L
LL
Buben
John
J
Craft
Trelia J
TJ
D000925:Anticoagulants / Q000737:chemistry; D000990:Antithrombin III / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000494:pharmacology*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005456:Fluorescent Dyes; D062367:ortho-Aminobenzoates; D000990:Antithrombin III; C000219:anthranilamide