Title :

Synthesis and SAR studies of novel isoquinoline and tetrahydroisoquinoline derivatives as melatonin receptor ligands.

Author(s) :

Ettaoussi, Mohamed [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Laversin, Amelie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Vreulz, Brandon [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Rami, Marouane [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Lebegue, Nicolas [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Delagrange, Philippe [Auteur]
Institut de Recherches SERVIER [IRS]
Caignard, Daniel Henri [Auteur]
Institut de Recherches SERVIER [IRS]
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Yous, Said [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Journal title :

ChemMedChem

Abbreviated title :

ChemMedChem

Volume number :

17

Pages :

e202100658

Publication date :

2021-11-19

ISSN :

1860-7187

Keyword(s) :

agomelatine
melatonin
MT1
MT2
isoquinoline
tetrahydroisoquinoline

English keyword(s) :

tetrahydroisoquinoline
isoquinoline
MT2
MT1
melatonin
agomelatine

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives ...
Show more >In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives were synthesized and pharmacologically evaluated. This isosteric replacement of the naphthalene group of agomelatine has led to potent agonist and partial agonist compounds with nanomolar melatonergic binding affinities. Overall, the presence of a nitrogen atom was accompanied with a decrease in the binding affinity toward both MT1 and MT2 and the loss of 5HT2C response, especially for tetrahydroisoquinoline in comparison with the parent compound. Interestingly, due to the presence of this nitrogen atom, a notable improvement in the pharmacokinetic properties was observed for all compounds.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-16T01:40:41Z
2024-11-25T12:57:15Z