sj-docx-1-npx-10.1177_1934578X231174312 - Supplemental material for Reducing Effect of a Standardized Extract of Apple Branches on Food Intake in Healthy, Nonobese Rats

Supplemental material, sj-docx-1-npx-10.1177_1934578X231174312 for Reducing Effect of a Standardized Extract of Apple Branches on Food Intake in Healthy, Nonobese Rats by Mauro A.M. Carai, Erika Sitzia, and Giancarlo Colombo in Natural Product Communications</p

Synthesis and Pharmacological Characterization of 2‑(Acylamino)thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABA_B Receptor

Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)­thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABA_B receptor by potentiating GTPγS stimulation induced by GABA at 2.5 and 25 μM while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds <b>6</b>, <b>10</b>, and <b>11</b> exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177