Investigation of factor Xa inhibitors containing non-amidine S1 elements.
Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombin time (PT).
Franciskovich
Jeffry B
JB
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. j.franciskovich@lilly.com
Masters
John J
JJ
Tinsley
Jennifer M
JM
Craft
Trelia J
TJ
Froelich
Larry L
LL
Gifford-Moore
Donetta S
DS
Klimkowski
Valentine J
VJ
Smallwood
Jeffrey K
JK
Smith
Gerald F
GF
Smith
Tommy
T
Towner
Richard R
RR
Weir
Leonard C
LC
Wiley
Michael R
MR
D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011517:Prothrombin Time; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D001555:Benzene Derivatives; D065427:Factor Xa Inhibitors; D011480:Protease Inhibitors; D015951:Factor Xa