title: Design of novel N-(2,4-dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as thymidine phosphorylase inhibitors, and flexible docking to a homology model.
abstract: A novel class of thymidine phosphorylase (TP) inhibitors has been designed based on analogy to the enzyme substrate as well as known inhibitors. Flexible docking studies, using a homology model of human TP, of the designed N-(2,4-dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as well as their synthetic precursors provide insight into the observed experimental trends in binding affinity.
authors.affiliation: Attenuon, L.L.C., San Diego, CA 92121, USA. price@attenuon.com
authors.forename: Melissa L P
authors.initials: ML
authors.lastname: Price
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Guida
authors.forename: Tara E
authors.initials: TE
authors.lastname: Jackson
authors.forename: Jason A
authors.initials: JA
authors.lastname: Nydick
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Gladstone
authors.forename: José C
authors.initials: JC
authors.lastname: Juarez
authors.forename: Fernando
authors.initials: F
authors.lastname: Doñate
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ternansky
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D040681:Structural Homology, Protein; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D013939:Thymidine Phosphorylase