1040004-43-0Relevant academic research and scientific papers
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.
INDAZOLE SULFONAMIDE DERIVATIVES AS INVERSE AGONISTS OF RETINOID-RELATED ORPHAN RECEPTOR GAMMA (ROR GAMMA (T))
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Paragraph 0183; 0184; 0210, (2018/01/03)
Indazole sulfonamide derivatives of formula (I), the pharmaceutically acceptable addition salts thereof, the hydrates and/or solvates thereof, and the use of same as inverse agonists of retinoid-related orphan receptor gamma RORγt are described. Pharmaceutical compositions including such compounds, as well as the use thereof for the topical and/or oral treatment of RORγt receptor-mediated inflammatory diseases, in particular acne, psoriasis and/or atopic dermatitis are also described.
SULFONAMIDE COMPOUNDS AND THEIR USE IN THE MODULATION RETINOID-RELATED ORPHAN RECEPTOR
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Paragraph 0203, (2014/09/03)
The present invention is directed to novel retinoid-related orphan receptor gamma (RORγ) modulators of formula (I), processes for their preparation, pharmaceutical compositions containing these modulators, and their use in the treatment of inflammatory, metabolic and autoimmune diseases mediated by RORγ wherein R1 to R7 are as defined in claim 35.
SULFONAMIDE COMPOUNDS AND THEIR USE IN THE MODULATION RETINOID - RELATED ORPHAN RECEPTOR
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Page/Page column 38-39, (2013/04/13)
The present invention is directed to novel retinoid-related orphan receptor gamma (RORy) modulators of formula (I), processes for their preparation, pharmaceutical compositions containing these modulators, and their use in the treatment of inflammatory, metabolic and autoimmune diseases mediated by RORy wherein R1 to R7 are as defined in claim 1.
