1363402-35-0Relevant articles and documents
Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: From hit to clinic
Pizzonero, Mathieu,Dupont, Sonia,Babel, Marielle,Beaumont, Stéphane,Bienvenu, Natacha,Blanqué, Roland,Cherel, La?titia,Christophe, Thierry,Crescenzi, Benedetta,De Lemos, Elsa,Delerive, Philippe,Deprez, Pierre,De Vos, Steve,Djata, Fatoumata,Fletcher, Stephen,Kopiejewski, Sabrina,Lebraly, Christelle,Lefran?ois, Jean-Michel,Lavazais, Stéphanie,Manioc, Murielle,Nelles, Luc,Oste, Line,Polancec, Denis,Quénéhen, Vanessa,Soulas, Florilène,Triballeau, Nicolas,Van Der Aar, Ellen M.,Vandeghinste, Nick,Wakselman, Emanuelle,Brys, Reginald,Saniere, Laurent
, p. 10044 - 10057 (2015/02/05)
FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic.
AZETIDINE DERIVATIVES USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES
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, (2012/08/07)
Compounds are disclosed that have a formula represented by the following: These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example inflammatory conditions, infectious diseases, autoimmune diseases, diseases involving impairment of immune cell functions, cardiometabolic diseases, and/or proliferative diseases.
