当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Privileged scaffold-based design to identify a novel drug-like 5-HT7 receptor-preferring agonist to target Fragile X syndrome.

Privileged scaffold-based design to identify a novel drug-like 5-HT7 receptor-preferring agonist to target Fragile X syndrome.

Abstract：

:Recent preclinical studies have shown that activation of the serotonin 5-HT7 receptor has the potential to treat neurodevelopmental disorders such as Fragile X syndrome, a rare disease characterized by autistic features. With the aim to provide the scientific community with diversified drug-like 5-HT7 receptor-preferring agonists, we designed a set of new long-chain arylpiperazines by exploiting structural fragments present in clinically approved drugs or in preclinical candidates (privileged scaffolds). The new compounds were synthesized, tested for their affinity at 5-HT7 and 5-HT1A receptors, and screened for their in vitro stability to microsomal degradation and toxicity. Selected compounds were characterized as 5-HT7 receptor-preferring ligands, endowed with high metabolic stability and low toxicity. Compound 7g emerged as a drug-like 5-HT7 receptor-preferring agonist capable to rescue synaptic plasticity and attenuate stereotyped behavior in a mouse model of Fragile X syndrome.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Lacivita E,Niso M,Stama ML,Arzuaga A,Altamura C,Costa L,Desaphy JF,Ragozzino ME,Ciranna L,Leopoldo M

doi

10.1016/j.ejmech.2020.112395

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

112395

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30365-2

journal_volume

199

pub_type

杂志文章

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