Non-covalent thrombin inhibitors featuring P(3)-heterocycles with P(1)-monocyclic arginine surrogates.
Investigations on P(2)-P(3)-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P(1)-arginine derivatives. The design, synthesis, and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P(1)-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydroxyamidines, (2) 2-aminopyrazines, and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines.
Reiner
John E
JE
Department of Medicinal Chemistry, Corvas International, Inc., 3030 Science Park Road, San Diego, CA 92121, USA.
Siev
Daniel V
DV
Araldi
Gian Luca
GL
Cui
Jingrong Jean
JJ
Ho
Jonathan Z
JZ
Reddy
Komandla Malla
KM
Mamedova
Lala
L
Vu
Phong H
PH
Lee
Kuen Shan S
KS
Minami
Nathaniel K
NK
Gibson
Tony S
TS
Anderson
Susanne M
SM
Bradbury
Annette E
AE
Nolan
Thomas G
TG
Semple
J Edward
JE
D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry*; D004285:Dogs; D006571:Heterocyclic Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000991:Antithrombins; D006571:Heterocyclic Compounds; D001120:Arginine