title: Microwave-enhanced medicinal chemistry: a high-speed opportunity for convenient preparation of protease inhibitors.
abstract: The unique properties of microwave in situ heating offer unparalleled opportunities for medicinal chemists to accelerate lead optimization processes in early drug discovery. The technology is ideal for palladium-catalyzed alteration chemistry as it allows for complete control over reactions, with the use of non-inert conditions, providing high chemoselectivity and rapid feedback. To illustrate the advantages of this methodology, we describe our applications and approaches for the rapid synthesis of novel aspartyl protease inhibitors using dedicated microwave equipment. Biological results from chemical studies of the different side-chain positions of HIV-1 and malarial plasmepsin I and II protease inhibitors are summarized.
authors.affiliation: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University Box 574, SE-751 23, Uppsala, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Ersmark
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
authors.forename: Johan
authors.initials: J
authors.lastname: Wannberg
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis; D006358:Hot Temperature; D008872:Microwaves; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin