Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human cytomegalovirus protease. Part 3: potency and plasma stability.
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.
Borthwick
Alan D
AD
Department of Medicinal Chemistry CVU UK, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK. adb3028@glaxowellcome.co.uk
Exall
Anne M
AM
Haley
Terry M
TM
Jackson
Deborah L
DL
Mason
Andrew M
AM
Weingarten
Gordon G
GG
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000201:enzymology*; D003619:Dansyl Compounds / Q000737:chemistry; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011480:Protease Inhibitors / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000998:Antiviral Agents; D003619:Dansyl Compounds; D007769:Lactams; D011480:Protease Inhibitors; D011759:Pyrrolidines; C086697:dansylproline; D011392:Proline