1775-71-9Relevant articles and documents
Structure optimization of positive allosteric modulators of GABAB receptors led to the unexpected discovery of antagonists/potential negative allosteric modulators
Mugnaini, Claudia,Brizzi, Antonella,Mostallino, Rafaela,Castelli, Maria Paola,Corelli, Federico
, (2020/08/06)
Positive allosteric modulators (PAMs) of GABAB receptor represent an interesting alternative to receptor agonists such as baclofen, as they act on the receptor in a more physiological way and thus are devoid of the side effects typically exerted by the agonists. Based on our interest in the identification of new GABAB receptor PAMs, we followed a merging approach to design new chemotypes starting from selected active compounds, such as GS39783, rac-BHFF, and BHF177, and we ended up with the synthesis of four different classes of compounds. The new compounds were tested alone or in the presence of 10 μM GABA using [35S]GTPγS binding assay to assess their functionality at the receptor. Unexpectedly, a number of them significantly inhibited GABA-stimulated GTPγS binding thus revealing a functional switch with respect to the prototype molecules. Further studies on selected compounds will clarify if they act as negative modulators of the receptor or, instead, as antagonists at the orthosteric binding site.
N1-substituted benzamidines: Synthesis, antiproteinase activity and inhibition of tumor cell growth
Ferroni,Simoni,Binato,Nastruzzi,Manfredini,Orlandini,Feriotto,Gambari
, p. 1311 - 1321 (2007/10/02)
We have synthesized N1-substituted benzamidines and polybenzamidines with the aim to produce antitumor drugs retaining differential biological properties with respect to unsubstituted compounds. Antiproliferative activity on in vitro cultured human leukemic cells was exhibited by N1-substituted polybenzamidines, while N1-substituted benzamidines were found to retain very low antitumor effects. Furthermore, our results suggest that N1-substituted benzamidines and some of polybenzamidines exhibit low activity on trypsin and kallikrein. Taken together these data indicate that some N1-substituted polybenzamidines could be of interest for experimental antitumor therapy, since are likey to retain low side effects due to alteration of proteinase activity.
