Design, synthesis, and in vitro biological activity of indole-based factor Xa inhibitors.
A series of indole and carbazole based inhibitors of factor Xa (FXa) has been investigated. The most potent compound inhibits FXa with a Ki of 0.2 nM and has 900- and 750-fold selectivity over thrombin and trypsin, respectively.
Arnaiz
D O
DO
Discovery Research, Berlex Biosciences, Richmond, CA 94804, USA. damian_arnaiz@berlex.com
Zhao
Z
Z
Liang
A
A
Trinh
L
L
Witlow
M
M
Koovakkat
S K
SK
Shaw
K J
KJ
D000578:Amidines / Q000737:chemistry*; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D065427:Factor Xa Inhibitors; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
D000578:Amidines; D000925:Anticoagulants; D002227:Carbazoles; D065427:Factor Xa Inhibitors; D007211:Indoles; D011725:Pyridines; D014361:Trypsin Inhibitors; C114592:Fidexaban; D013917:Thrombin