《Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for “”Diabesity””》 was written by Decara, Juan M.; Vazquez-Villa, Henar; Brea, Jose; Alonso, Monica; Srivastava, Raj Kamal; Orio, Laura; Alen, Francisco; Suarez, Juan; Baixeras, Elena; Garcia-Carceles, Javier; Escobar-Pena, Andrea; Lutz, Beat; Rodriguez, Ramon; Codesido, Eva; Garcia-Ladona, F. Javier; Bennett, Teresa A.; Ballesteros, Juan A.; Cruces, Jacobo; Loza, Maria I.; Benhamu, Bellinda; Rodriguez de Fonseca, Fernando; Lopez-Rodriguez, Maria L.. Recommanded Product: 39546-32-2 And the article was included in Journal of Medicinal Chemistry on April 14 ,2022. The article conveys some information:
Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small mols. acting as pos. allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-mol. PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes. The results came from multiple reactions, including the reaction of Piperidine-4-carboxamide(cas: 39546-32-2Recommanded Product: 39546-32-2)
Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Recommanded Product: 39546-32-2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem