Polycyclic systems containing 1,2,4-oxadiazole ring 2. 4-(1,2,4-Oxadiazol-5-yl)pyrrolidin-2-ones: Synthesis and prediction of biological activity

Abstract

The intensive use of the 1,2,4-oxadiazole (isoxadiazole) system in medicinal chemistry [2][3][4] as bioisosteres of carboxylic acid esters and amides [5,6] makes the question of the development and optimization of methods for their synthesis timely. There is particular interest in compounds whose molecules have an isoxadiazole ring combined with another heterocyclic pharmacophore as this may lead to compounds having a broader spectrum of biological activity.As subjects for this investigation we chose compounds whose molecules would contain a pyrrolidin-2-one ring along with the 1,2,4-oxadiazole. It is known that the isoxadiazole system is a component of antiviralPicovir) [7], antiglaucomal, cardiovascular (Proxodolol) [8] and other medicinal compounds [9-11]. Neurological (Etiracetam, Memolog) [12, 13], respiratory (Rolipram) [14], immunostimulatory (Pidotimod) [15] and other medicinal preparations [16-20] are found amongst pyrrolidin-2-one derivatives.In [21] routes were reported for the synthesis of 3-(1,2,4-oxadiazol-5-yl)pyrrolidin-2-ones based on the preparatively inconvenient reaction of substituted 3-cyanopyrrolidin-2-ones with N-hydroxybenzimidoyl chlorides or on the acid catalyzed reaction of the difficult to obtain 5-amino-4-(1,2,4-oxadiazol-5-yl)-2,3-dihydropyrroles. Information concerning the target 4-(1,2,4-oxadiazol-5-yl)pyrrolidin-2-ones has not appeared in the literature. For their preparation we have taken advantage of the method of parallel liquid phase synthesis based on a one-pot condensation of 5-oxopyrrolidine-3-carboxylic acids, carbodiimidazole (CDI), _______ * For Communication 1 see [1] __________________________________________________________________________________________ V. N.

Discovery of novel heterocyclic derivatives containing oxadiazolone or pyrimidinone cores as DPP‐4 inhibitors

“…The residue was recrystallized from chloroform/hexane. All compounds 2a [55] , 2b [56] , 2c [57], 2d [58] , 2e [57] , 2f [59] , 2g [60] , 2h, and 2i [57] were previously described and had their data compared to the literature data.…”

Novel potent HIF-1 inhibitors for the prevention of tumor metastasis: discovery and optimization of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives

“…In the compounds 1 and 2a-2l, the 5-(N-benzyl-indazole)-1,2,4oxadiazole skeleton was retained and various alkyl and aryl groups were examined as an R 1 moiety to nd an optimal substituent. Condensation of alkyl or aryl nitriles 6a-l with hydroxylamine gave the intermediates 7a-l. 30 Esterication of compound 8 with MeOH and thionyl chloride led to compound 9, benzylation of which with 4-chlorobenzyl chloride gave compound 10. Hydrolysis of 10 gave 11, which was condensed with 7a-l to afford compounds 2a-2l (Scheme 1).…”