Guanylpiperidine peptidomimetics: potent and selective bis-cation inhibitors of factor Xa.
A novel series of rigid P3-guanylpiperidine peptide mimics 3-14 was designed as potential factor Xa and prothrombinase inhibitors. Incorporation into a P2-gly-P1-argininal motif led to highly potent and selective inhibitors. The synthesis and biological activities of these derivatives are reported herein.
Tamura
S Y
SY
Corvas International, Inc., Department of Medicinal Chemistry, San Diego, CA 92121, USA.
Levy
O E
OE
Uong
T H
TH
Reiner
J E
JE
Goldman
E A
EA
Ho
J Z
JZ
Cohen
C R
CR
Bergum
P W
PW
Nutt
R F
RF
Brunck
T K
TK
Semple
J E
JE
D002412:Cations; D065427:Factor Xa Inhibitors; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D002412:Cations; D065427:Factor Xa Inhibitors; D010455:Peptides; D010880:Piperidines; D015842:Serine Proteinase Inhibitors; D006147:Guanine