title: High-throughput synthesis and optimization of thrombin inhibitors via urazole alpha-addition and Michael addition.
abstract: 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.
authors.affiliation: Molecumetics, 2023 120th Ave NE, Bellevue, WA 98005, USA. dboatman@arenapharm.com
authors.forename: P Douglas
authors.initials: PD
authors.lastname: Boatman
authors.forename: Jan
authors.initials: J
authors.lastname: Urban
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.forename: Maher
authors.initials: M
authors.lastname: Qabar
authors.forename: Michael
authors.initials: M
authors.lastname: Kahn
mesh_terms: 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
chemical_list: D000480:Alkynes; D011422:Propionates; D015842:Serine Proteinase Inhibitors; D014230:Triazoles; D013917:Thrombin; C011537:propiolic acid; C421465:urazole