High-throughput synthesis and optimization of thrombin inhibitors via urazole alpha-addition and Michael addition.
A novel alpha-addition of propiolates to urazoles followed by Michael addition of a variety of nucleophiles has been developed for rapid production and optimization of peptidomimetic drug leads. This technology has produced a number of highly potent and selective inhibitors of the serine protease, thrombin.
Boatman
P Douglas
PD
Molecumetics, 2023 120th Ave NE, Bellevue, WA 98005, USA. dboatman@arenapharm.com
Urban
Jan
J
Nguyen
Minh
M
Qabar
Maher
M
Kahn
Michael
M
D000480:Alkynes / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D018716:Molecular Mimicry; D011422:Propionates / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000480:Alkynes; D011422:Propionates; D015842:Serine Proteinase Inhibitors; D014230:Triazoles; D013917:Thrombin; C011537:propiolic acid; C421465:urazole