Thrombin inhibitors built on an azaphenylalanine scaffold.
A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the P1 position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis.
Zega
Anamarija
A
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Mlinsek
Gregor
G
Solmajer
Tomaz
T
Trampus-Bakija
Alenka
A
Stegnar
Mojca
M
Urleb
Uros
U
D001372:Aza Compounds / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D001372:Aza Compounds; D015842:Serine Proteinase Inhibitors; D010649:Phenylalanine; D013917:Thrombin