In this work, further structural investigations on the 8-amino-2-phenyl-6-aryl-1,2,4-triazolo[4,3-a]pyrazin-3-one series were carried out to achieve potent and selective human A2A adenosine receptor (AR) antagonists. Different ether and amide moieties were attached at the para-position of the 6-phenyl ring, thus leading to compounds 1–9 and 10–18, respectively. Most of these moieties contained terminal basic rings (pyrrolidine, morpholine, piperidine and substituted piperazines) which were thought to confer good physicochemical and drug-like properties. Compounds 11–16, bearing the amide linker, possessed high affinity and selectivity for the hA2A AR (Ki = 3.6–11.8 nM). Also derivatives 1–9, featuring an ether linker, preferentially targeted the hA2A AR but with lower affinity, compared to those of the relative amide compounds. Docking studies, carried out at the hA2A AR binding site, highlighted some crucial ligand-receptor interactions, particularly those provided by the appended substituent whose nature deeply affected hA2A AR affinity.
New 8-amino-1,2,4-triazolo[4,3-a]pyrazin-3-one derivatives. Evaluation of different moieties on the 6-aryl ring to obtain potent and selective human A2A adenosine receptor antagonists / Falsini M.; Ceni C.; Catarzi D.; Varano F.; Dal Ben D.; Marucci G.; Buccioni M.; Marti Navia A.; Volpini R.; Colotta V.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - ELETTRONICO. - 30:(2020), pp. 127126-127126. [10.1016/j.bmcl.2020.127126]
New 8-amino-1,2,4-triazolo[4,3-a]pyrazin-3-one derivatives. Evaluation of different moieties on the 6-aryl ring to obtain potent and selective human A2A adenosine receptor antagonists
Falsini M.;Ceni C.;Catarzi D.;Varano F.;Colotta V.
2020
Abstract
In this work, further structural investigations on the 8-amino-2-phenyl-6-aryl-1,2,4-triazolo[4,3-a]pyrazin-3-one series were carried out to achieve potent and selective human A2A adenosine receptor (AR) antagonists. Different ether and amide moieties were attached at the para-position of the 6-phenyl ring, thus leading to compounds 1–9 and 10–18, respectively. Most of these moieties contained terminal basic rings (pyrrolidine, morpholine, piperidine and substituted piperazines) which were thought to confer good physicochemical and drug-like properties. Compounds 11–16, bearing the amide linker, possessed high affinity and selectivity for the hA2A AR (Ki = 3.6–11.8 nM). Also derivatives 1–9, featuring an ether linker, preferentially targeted the hA2A AR but with lower affinity, compared to those of the relative amide compounds. Docking studies, carried out at the hA2A AR binding site, highlighted some crucial ligand-receptor interactions, particularly those provided by the appended substituent whose nature deeply affected hA2A AR affinity.File | Dimensione | Formato | |
---|---|---|---|
BioorgMedChemLett_2020_30_Author_copy.pdf
Accesso chiuso
Descrizione: Articolo principale
Tipologia:
Pdf editoriale (Version of record)
Licenza:
Tutti i diritti riservati
Dimensione
2.94 MB
Formato
Adobe PDF
|
2.94 MB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.