Relationship between structural properties and affinity for herpes simplex virus type 1 thymidine kinase of bromine substituted 5-heteroaromatic 2'-deoxyuridines.
The crystal structures of 5-(5-furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (IV) and 5-(3-bromothien-2-yl)-2'-deoxyuridine (V) have been studied in order to explain the different affinity of the compounds for the herpes simplex virus type 1 (HSV-1) thymidine kinase. These compounds present a variable affinity according to the position of the heteroatom substituting the five-membered ring. An unfavourable substitution in the five-membered ring for interaction with the HSV-1 thymidine kinase has been identified.
Creuven
I
I
Laboratoire de Chimie Moléculaire Structurale, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Evrard
C
C
Olivier
A
A
Evrard
G
G
Van Aerschot
A
A
Wigerinck
P
P
Herdewijn
P
P
Durant
F
F
D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism*; D001966:Bromine; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism*; D014961:X-Ray Diffraction
D000998:Antiviral Agents; D013876:Thiophenes; C070460:5-(5-bromothien-2-yl)-2'-deoxyuridine; D013937:Thymidine Kinase; D001966:Bromine; D003857:Deoxyuridine