Lysine sulfonamides as novel HIV-protease inhibitors: optimization of the Nepsilon-acyl-phenyl spacer.
A series of Nalpha-isobutyl-Nalpha-arylsulfonamido-(Nepsilon acyl) lysine and lysinol derivatives were prepared and evaluated as inhibitors of HIV protease and wild type virus. A simple original synthesis was devised to form Nalpha-(arylsulfonamide)-Nalpha-isobutyl lysine, which could be easily acylated with carboxylic acids at the Nepsilon position. A two-atom spacer was found to be optimal between this acyl group and a phenyl yielding compounds of sub-nanomolar potency on purified enzyme.
Stranix
Brent R
BR
Pharmacor Inc, 535 Cartier West, blvd, Laval, Quebec, Canada H7V 3S8. bstranix@procyonbiopharm.com
Sauvé
Gilles
G
Bouzide
Abderrahim
A
Coté
Alexandre
A
Sévigny
Guy
G
Yelle
Jocelyn
J
D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D008239:Lysine