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 w...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 13; no. 1; pp. 107 - 110
Main Authors:	Price, MelissaL.P., Guida, WayneC, Jackson, TaraE, Nydick, JasonA, Gladstone, PatriciaL, Juarez, JoséC., Doñate, Fernando, Ternansky, RobertJ
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 06-01-2003 Elsevier
Subjects:	Antineoplastic agents Binding Sites Biological and medical sciences Computer Simulation Drug Design Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology General aspects Guanidines - chemistry Guanidines - pharmacology Humans Medical sciences Models, Molecular Pharmacology. Drug treatments Protein Binding Structural Homology, Protein Thymidine Phosphorylase - antagonists & inhibitors Sulfur nitrogen heterocycle Enzyme Transferases Glycosyltransferases Enzyme inhibitor Homology Guanidines In vitro Modeling Biological activity Molecular model Bicyclic compound Chemical synthesis Pentosyltransferases Thymidine phosphorylase Conformation
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Summary:	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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(02)00828-4