Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 1: Weakly basic azoles.
Despite their relatively weak basicity, simple azoles, specifically imidazoles and aminothiazoles, can function as potent surrogates for the more basic amines (e.g., alkyl amines, amidines, guanidines, etc.) which are most often employed as the P1 ligand in the design of noncovalent small molecule inhibitors of thrombin.
Isaacs
Richard C A
RC
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. richard_isaacs@merck.com
Solinsky
Mark G
MG
Cutrona
Kellie J
KJ
Newton
Christina L
CL
Naylor-Olsen
Adel M
AM
Krueger
Julie A
JA
Lewis
S Dale
SD
Lucas
Bobby J
BJ
D001393:Azoles / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000187:drug effects
D001393:Azoles; D004791:Enzyme Inhibitors; D008024:Ligands; D014357:Trypsin; D013917:Thrombin