Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human cytomegalovirus protease. Part 3: potency and plasma stability

Alan D Borthwick; Anne M Exall; Terry M Haley; Deborah L Jackson; Andrew M Mason; Gordon G Weingarten

doi:10.1016/s0960-894x(02)00294-9

Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human cytomegalovirus protease. Part 3: potency and plasma stability

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1719-22. doi: 10.1016/s0960-894x(02)00294-9.

Authors

Alan D Borthwick¹, Anne M Exall, Terry M Haley, Deborah L Jackson, Andrew M Mason, Gordon G Weingarten

Affiliation

¹ Department of Medicinal Chemistry CVU UK, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK. [email protected]

PMID: 12067545
DOI: 10.1016/s0960-894x(02)00294-9

Abstract

Mechanism-based inhibitors of HCMV protease, which are stable to human plasma (> or = 20 h) and have single-figure potency in the microM range against HCMV protease, have been developed based on the dansylproline alpha-methyl pyrrolidine-5,5-trans-lactam nucleus.

MeSH terms

Antiviral Agents / chemistry*
Antiviral Agents / pharmacology*
Cytomegalovirus / enzymology*
Dansyl Compounds / chemistry
Drug Stability
Half-Life
Humans
Inhibitory Concentration 50
Lactams / blood
Lactams / chemistry
Lactams / pharmacology*
Proline / analogs & derivatives*
Proline / chemistry
Protease Inhibitors / blood
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Pyrrolidines / blood
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology*
Spectrometry, Mass, Electrospray Ionization

Substances

Antiviral Agents
Dansyl Compounds
Lactams
Protease Inhibitors
Pyrrolidines
dansylproline
Proline