MF-8, a novel promising arylpiperazine-hydantoin based 5-HT 7 receptor antagonist: In vitro drug-likeness studies and in vivo pharmacological evaluation

Bioorganic & Medicinal Chemistry Letters
2018.0

Abstract

We report the in vitro drug-likeness studies and in vivo pharmacological evaluation for a new potent 5-HT7 receptor antagonist MF-8 (5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylhydantoin). The in vitro tests showed good permeability, very good metabolic stability, low risk of drug-drug interactions and satisfying safety profile. Moreover, MF-8 showed excellent antidepressant-like activity in the forced swim test in rodents and promising anxiolytic-like activity in the four-plate test in mice. Regarding the potent affinity, high selectivity and antagonistic activity of MF-8 for the 5-HT7 receptor as well as excellent drug - like properties in vitro and confirmed in vivo pharmacological activity, MF-8 should be considered as a very significant molecule in the search for a new class of anti-depressant drugs.

Knowledge Graph

Similar Paper

MF-8, a novel promising arylpiperazine-hydantoin based 5-HT 7 receptor antagonist: In vitro drug-likeness studies and in vivo pharmacological evaluation
Bioorganic & Medicinal Chemistry Letters 2018.0
Computer-aided insights into receptor-ligand interaction for novel 5-arylhydantoin derivatives as serotonin 5-HT 7 receptor agents with antidepressant activity
European Journal of Medicinal Chemistry 2018.0
Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression
Bioorganic & Medicinal Chemistry 2014.0
Novel anilide and benzylamide derivatives of arylpiperazinylalkanoic acids as 5-HT1A/5-HT7 receptor antagonists and phosphodiesterase 4/7 inhibitors with procognitive and antidepressant activity
European Journal of Medicinal Chemistry 2020.0
Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT 1A /5-HT 7
European Journal of Medicinal Chemistry 2018.0
Novel N-acyl-carbazole derivatives as 5-HT7R antagonists
European Journal of Medicinal Chemistry 2016.0
Novel multitarget 5-arylidenehydantoins with arylpiperazinealkyl fragment: Pharmacological evaluation and investigation of cytotoxicity and metabolic stability
Bioorganic & Medicinal Chemistry 2019.0
The influence of modifications in imide fragment structure on 5-HT1A and 5-HT7 receptor affinity and in vivo pharmacological properties of some new 1-(m-trifluoromethylphenyl)piperazines
Bioorganic & Medicinal Chemistry 2007.0
Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7
Bioorganic & Medicinal Chemistry Letters 2019.0
The impact of the halogen bonding on D 2 and 5-HT 1A /5-HT 7 receptor activity of azinesulfonamides of 4-[(2-ethyl)piperidinyl-1-yl]phenylpiperazines with antipsychotic and antidepressant properties
Bioorganic & Medicinal Chemistry 2017.0