Pharmacophore-Based Design of Novel Oxadiazoles as Selective Sphingosine-1-phosphate (S1P) Receptor Agonists with in vivo Efficacy was written by Quattropani, Anna;Sauer, Wolfgang H. B.;Crosignani, Stefano;Dorbais, Jerome;Gerber, Patrick;Gonzalez, Jerome;Marin, Delphine;Muzerelle, Mathilde;Beltran, Fanny;Nichols, Anthony;Georgi, Katrin;Schneider, Manfred;Vitte, Pierre-Alain;Eligert, Valerie;Novo-Perez, Laurence;Hantson, Jennifer;Nock, Sebastien;Carboni, Susanna;Soares de Souza, Adriano Luis;Arrighi, Jean-Francois;Boschert, Ursula;Bombrun, Agnes. And the article was included in ChemMedChem in 2015.Recommanded Product: 107317-58-8 This article mentions the following:
Sphingosine-1-phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure-activity relation exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five-membered heterocycles, and the use of diverse 2,2′-disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochem. properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds From these optimization studies, a selective S1P1 agonist, N-methyl-N-(4-{5-[2-methyl-2′-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (45), and a dual S1P1,5 agonist, N-methyl-N-(3-{5-[2′-methyl-2-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (49), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head-to-head in an exptl. autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan-S1P receptor agonist, S1P1,5 agonist 49 demonstrated comparable efficacy while S1P1-selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8Recommanded Product: 107317-58-8).
Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon闂佺偨鍎茶ぐ绲﹐mine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Recommanded Product: 107317-58-8
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary