title: Stereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU.
abstract: Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme.
authors.affiliation: Laboratoire de Chimie Moléculaire Structurale, Facultés Universitaires N.-D. de la Paix, Namur, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Olivier
authors.forename: I
authors.initials: I
authors.lastname: Creuven
authors.forename: C
authors.initials: C
authors.lastname: Evrard
authors.forename: G
authors.initials: G
authors.lastname: Evrard
authors.forename: M
authors.initials: M
authors.lastname: Dory
authors.forename: A
authors.initials: A
authors.lastname: van Aerschot
authors.forename: P
authors.initials: P
authors.lastname: Wigerinck
authors.forename: P
authors.initials: P
authors.lastname: Herdewijn
authors.forename: F
authors.initials: F
authors.lastname: Durant
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D015394:Molecular Structure; D013237:Stereoisomerism; D013816:Thermodynamics; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology; D013937:Thymidine Kinase / Q000737:chemistry / Q000187:drug effects; D014764:Viral Proteins / Q000737:chemistry / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D000998:Antiviral Agents; D013876:Thiophenes; D014764:Viral Proteins; C070461:5-(5-chlorothien-2-yl)-2'-deoxyuridine; C020235:brivudine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D003857:Deoxyuridine