Synthesis and SAR studies on azetidine-containing dipeptides as HCMV inhibitors.
SAR studies on an azetidine-containing dipeptide prototype inhibitor of HCMV are described. Three series of structurally modified analogues, involving substitutions at the N- and C-terminus, and at the C-terminal side-chain were synthesized and evaluated for antiviral activity. Aliphatic or no substituents at the C-carboxamide group, an aliphatic C-terminal side-chain, as well as a benzyloxycarbonyl moiety at the N-terminus were absolute requirements for anti-HCMV activity. The conformational restriction induced by the 2-azetidine residue into the dipeptide derivatives, identified by (1)H NMR as a γ-type reverse turn, seems to have influence on the activity of these molecules.
Instituto de Química Médica (CSIC), Juna de la Cierva, 3, 28006 Madrid, Spain.
Paula
P
Pérez-Faginas
M Teresa
MT
Aranda
M Teresa
MT
García-López
Robert
R
Snoeck
Graciela
G
Andrei
Jan
J
Balzarini
Rosario
R
González-Muñiz
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001384:Azetidines; D004151:Dipeptides
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