| Title: |
Novel Quinazoline Derivatives as Highly Effective A2A Adenosine Receptor Antagonists. |
| Authors: |
Laversin, Amelie; Dufossez, Robin; Bolteau, R.; Duroux, R.; Ravez, Severine; Hernandez-Tapia, S.; Fossart, Martin; Coevoet, Mathilde; Liberelle, Maxime; Yous, Said; Lebegue, Nicolas; Melnyk, Patricia |
| Contributors: |
Lille Neurosciences & Cognition - U 1172 (LilNCog); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc); Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille |
| Source: |
ISSN: 1420-3049 ; Molecules ; https://hal.univ-lille.fr/hal-04977456 ; Molecules, 2024, Molecules, 29 (16), pp.3847. ⟨10.3390/molecules29163847⟩. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2024 |
| Collection: |
LillOA (HAL Lille Open Archive, Université de Lille) |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; first_pagesettingsOrder Article ReprintsOpen AccessArticleNovel Quinazoline Derivatives as Highly Effective A2A Adenosine Receptor Antagonistsby Amélie Laversin, Robin Dufossez†, Raphaël Bolteau† [ORCID] , Romain Duroux, Séverine Ravez, Sergio Hernandez-Tapia, Martin Fossart, Mathilde Coevoet[ORCID] , Maxime Liberelle, Saïd Yous, Nicolas Lebègue[ORCID] and Patricia Melnyk* [ORCID]Univ. Lille, Inserm, CHU Lille, U1172—LilNCog—Lille Neuroscience & Cognition, F-59000 Lille, France*Author to whom correspondence should be addressed.†These authors contributed equally to this work.Molecules 2024, 29(16), 3847; https://doi.org/10.3390/molecules29163847Submission received: 11 July 2024 / Revised: 31 July 2024 / Accepted: 5 August 2024 / Published: 14 August 2024(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry III)Downloadkeyboard_arrow_downBrowse FiguresReview Reports Versions NotesAbstractThe adenosine A2A receptor (A2AR) has been identified as a therapeutic target for treating neurodegenerative diseases and cancer. In recent years, we have highlighted the 2-aminoquinazoline heterocycle as an promising scaffold for designing new A2AR antagonists, exemplified by 6-bromo-4-(furan-2-yl)quinazolin-2-amine 1 (Ki (hA2AR) = 20 nM). Here, we report the synthesis of new 2-aminoquinazoline derivatives with substitutions at the C6- and C7-positions, and the introduction of aminoalkyl chains containing tertiary amines at the C2-position to enhance antagonist activity and solubility properties. Compound 5m showed a high affinity for hA2AR with a Ki value of 5 nM and demonstrated antagonist activity with an IC50 of 6 µM in a cyclic AMP assay. Introducing aminopentylpiperidine and 4-[(piperidin-1-yl)methyl]aniline substituents maintained the binding affinities (9x, Ki = 21 nM; 10d, Ki = 15 nM) and functional antagonist activities (9x, IC50 = 9 µM; 10d, IC50 = 5 µM) of the synthesized compounds while improving solubility. This study provides insights into the future development ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39202926; PUBMED: 39202926 |
| DOI: |
10.3390/molecules29163847 |
| Availability: |
https://hal.univ-lille.fr/hal-04977456; https://hal.univ-lille.fr/hal-04977456v1/document; https://hal.univ-lille.fr/hal-04977456v1/file/molecules-29-03847.pdf; https://doi.org/10.3390/molecules29163847 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.23EC8DE9 |
| Database: |
BASE |