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.
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.
Price
Melissa L P
ML
Attenuon, L.L.C., San Diego, CA 92121, USA. price@attenuon.com
Guida
Wayne C
WC
Jackson
Tara E
TE
Nydick
Jason A
JA
Gladstone
Patricia L
PL
Juarez
José C
JC
Doñate
Fernando
F
Ternansky
Robert J
RJ
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*
D004791:Enzyme Inhibitors; D006146:Guanidines; D013939:Thymidine Phosphorylase