Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors.
Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.
Franciskovich
Jeffry B
JB
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Masters
John J
JJ
Weber
Wayne W
WW
Klimkowski
Valentine J
VJ
Chouinard
Michael
M
Sipes
Philip R
PR
Johnson
Lea M
LM
Snyder
David W
DW
Chastain
Marcia K
MK
Craft
Trelia J
TJ
Towner
Richard D
RD
Gifford-Moore
Donetta S
DS
Froelich
Larry L
LL
Smallwood
Jeffrey K
JK
Foster
Ronald S
RS
Smith
Gerald F
GF
Liebeschuetz
John W
JW
Murray
Christopher W
CW
Young
Stephen C
SC
D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000990:Antithrombin III / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000925:Anticoagulants; C470025:phenylglycinamide; D000990:Antithrombin III; D015951:Factor Xa; D005998:Glycine