Polycyclic nitrogen heterocycles as potential thymidine phosphorylase inhibitors: synthesis, biological evaluation, and molecular docking study.


Journal

Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203

Informations de publication

Date de publication:
Dec 2022
Historique:
entrez: 22 12 2021
pubmed: 23 12 2021
medline: 3 3 2022
Statut: ppublish

Résumé

New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phosphorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four series have been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series B and C), the polycyclic heterocycle has been replaced by a pyrimidopyridopyrrolidinetetraone (series D). In each series, the tricyclic nitrogen heterocyclic moiety has been synthesised by a one-pot multicomponent reaction. Compared to

Identifiants

pubmed: 34933639
doi: 10.1080/14756366.2021.2001806
pmc: PMC8725971
doi:

Substances chimiques

Enzyme Inhibitors 0
Heterocyclic Compounds 0
Polycyclic Compounds 0
TYMP protein, human EC 2.4.2.4
Thymidine Phosphorylase EC 2.4.2.4
Nitrogen N762921K75

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

252-268

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Auteurs

Karen Aknin (K)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Alexis Bontemps (A)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Amaury Farce (A)

Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Université de Lille, Lille, France.

Eric Merlet (E)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Philippe Belmont (P)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Philippe Helissey (P)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Philippe Chavatte (P)

Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Université de Lille, Lille, France.

Marie-Agnès Sari (MA)

Faculté des Sciences, CNRS, UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université de Paris, Paris, France.

Sylviane Giorgi-Renault (S)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

Stéphanie Desbène-Finck (S)

Faculté de Santé, Faculté de Pharmacie de Paris, Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR8038, Université de Paris, Paris, France.

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Classifications MeSH