Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co-crystal structure.
Prototypical thrombin inhibitors were synthesized based on a trisubstituted phenol as a core motif. A naphthylsulfonamide analogue showed excellent antithrombin activity. An X-ray co-crystal structure showed the expected interactions.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, PQ, Canada H3C 3J7. stephen.hanessian@umontreal.ca
Therrien
Eric
E
van Otterlo
Willem A L
WA
Bayrakdarian
Malken
M
Nilsson
Ingemar
I
Fjellström
Ola
O
Xue
Yafeng
Y
D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D000991:Antithrombins; D010636:Phenols; D013917:Thrombin