6-Aryl-quinazolines as novel GABAB receptor positive allosteric modulators

József Huszár; József Levente Petró; Zsuzsa Hadady; Amrita Ágnes Bobok; Katalin Sághy; Attila Sándor Halász; Gábor Hornyánszky; Viktor Román; István Greiner; János Éles

doi:10.1016/j.bmcl.2022.128714

6-Aryl-quinazolines as novel GABA_B receptor positive allosteric modulators

Bioorg Med Chem Lett. 2022 Jul 1:67:128714. doi: 10.1016/j.bmcl.2022.128714. Epub 2022 Apr 1.

Affiliations

¹ Chemical Works of Gedeon Richter Plc, 30-32 Gyömrői Street, Budapest H-1103, Hungary. Electronic address: jo.huszar@richter.hu.
² Chemical Works of Gedeon Richter Plc, 30-32 Gyömrői Street, Budapest H-1103, Hungary.
³ Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 8 Budafoki Street, Budapest H-1111, Hungary.

PMID: 35367591
DOI: 10.1016/j.bmcl.2022.128714

Abstract

The systemic use of GABA_B orthosteric agonist baclofen might be limited due to its detrimental properties: sedation and motor impairment. In contrast, GABA_B positive allosteric modulators produce less adverse effects. Using BHF-177 as a starting point, we found a new active scaffold: the 6-aryl-quinazoline scaffold. Further elaborating the scaffold, we identified several in vitro and in vivo active compounds.

Keywords: GABA; GABA(B) receptor; PAMs; Positive allosteric modulators; γ-Aminobutyric acid.

MeSH terms

Allosteric Regulation
Baclofen
GABA-B Receptor Agonists* / pharmacology
Quinazolines / pharmacology
Receptors, GABA-B*

Substances

GABA-B Receptor Agonists
Quinazolines
Receptors, GABA-B
Baclofen