67589-15-5Relevant articles and documents
ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION
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Paragraph 1165, (2021/10/11)
The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, st
Discovery, Structure-Activity Relationship, and Antiparkinsonian Effect of a Potent and Brain-Penetrant Chemical Series of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4
Charvin, Delphine,Pomel, Vincent,Ortiz, Millan,Frauli, Mélanie,Scheffler, Sophie,Steinberg, Edith,Baron, Luc,Deshons, Laurène,Rudigier, Rachel,Thiarc, Delphine,Morice, Christophe,Manteau, Baptiste,Mayer, Stanislas,Graham, Danielle,Giethlen, Bruno,Brugger, Nadia,Hédou, Ga?l,Conquet, Fran?ois,Schann, Stephan
supporting information, p. 8515 - 8537 (2017/11/03)
The metabotropic glutamate receptor 4 (mGluR4) is an emerging target for the treatment of Parkinson's disease (PD). However, since the discovery of its therapeutic potential, no ligand has been successfully developed enough to be tested in the clinic. In the present paper, we report for the first time the medicinal chemistry efforts conducted around the pharmacological tool (-)-PHCCC. This work led to the identification of compound 40, a potent and selective mGluR4 positive allosteric modulator (PAM) with good water solubility and demonstrating consistent activity across validated preclinical rodent models of PD motor symptoms after intraperitoneal administration: haloperidol-induced catalepsy in mouse and the rat 6-hydroxydopamine (6-OHDA) lesion model. Moreover, we also describe the identification of compound 60 a close analogue of compound 40 with improved pharmacokinetic profile after oral administration. On the basis of its favorable and unique preclinical profile, compound 60 (PXT002331, now foliglurax) was nominated as a candidate for clinical development.
CHEMICAL COMPOUNDS
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Page/Page column 67, (2012/02/01)
The invention relates to new sulfonamide Nav1.7 inhibitors and pharmaceutically acceptable salts thereof, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. Nav 1.7 in