902306-92-7Relevant academic research and scientific papers
New 1,2,4-oxadiazole derivatives with positive mGlu4 receptor modulation activity and antipsychotic-like properties
Stankiewicz, Anna,Kaczorowska, Katarzyna,Bugno, Ryszard,Kozio?, Aneta,Paluchowska, Maria H.,Burnat, Grzegorz,Chru?cicka, Barbara,Chorobik, Paulina,Brański, Piotr,Wierońska, Joanna M.,Duszyńska, Beata,Pilc, Andrzej,Bojarski, Andrzej J.
, p. 211 - 225 (2021/12/21)
Considering the allosteric regulation of mGlu receptors for potential therapeutic applications, we developed a group of 1,2,4-oxadiazole derivatives that displayed mGlu4 receptor positive allosteric modulatory activity (EC50 = 282–656 nM). Selectivity screening revealed that they were devoid of activity at mGlu1, mGlu2 and mGlu5 receptors, but modulated mGlu7 and mGlu8 receptors, thus were classified as group III-preferring mGlu receptor agents. None of the compounds was active towards hERG channels or in the mini-AMES test. The most potent in?vitro mGlu4 PAM derivative 52 (N-(3-chloro-4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)phenyl)picolinamide) was readily absorbed after i.p. administration (male Albino Swiss mice) and reached a maximum brain concentration of 949.76 ng/mL. Five modulators (34, 37, 52, 60 and 62) demonstrated significant anxiolytic- and antipsychotic-like properties in the SIH and DOI-induced head twitch test, respectively. Promising data were obtained, especially for N-(4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)picolinamide (62), whose effects in the DOI-induced head twitch test were comparable to those of clozapine and better than those reported for the selective mGlu4 PAM ADX88178.
1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III
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, (2020/12/16)
The present invention relates to the novel 1,2,4-oxadiazole derivatives of general Formula I, wherein A, B, M, X, Y, R 1 , R 2 and R 3 are defined in the application. The compounds of the invention are modulators of metabotropic glutamate receptors that b
Design, synthesis and biological evaluation of some oxadiazole derivatives as novel amide-based inhibitors of soluble epoxide hydrolase
Rezaee, Elham,Hedayati, Mahdi,Rad, Laleh Hoghooghi,Kiani, Azin,Shahhosseini, Soraya,Faizi, Mehrdad,Tabatabai, Sayyed Abbas
, p. 721 - 730 (2014/07/07)
Soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators which are involved in the regulation of blood pressure and inflammation. Although the most reported potent sEH inhibitors are urea derivatives, these compounds have limited pharmacokinetic profile. In order to improve physicochemical properties, besides having favorable potency, amide non-urea derivatives with oxadiazole ring as a novel secondary pharmacophore against sEH enzyme were developed. Most of the novel compounds with appropriate physical properties, had comparable in vitro sEH inhibitory activity to 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a potent urea-based sEH inhibitor. The IC50value of the most potent compound (15c) was 0.43 nM.
