Design, synthesis and biological evaluation of novel 7-azaspiro[3.5]nonane derivatives as GPR119 agonists

Practical and Modular Construction of C(sp3)-Rich Alkyl Boron Compounds

“…The solution was filtered and concentrated under reduced vacuum to afford a light yellow residue, which was purified by chromatography (silica gel, 2:1 hexanes : ethyl acetate) to give the sulfone 159 as a white solid (18.6 mg, 80% yield). NMR spectroscopic data matches that reported in the literature 44 . TLC: Rf = 0.56 (3:1 hexanes : ethyl acetate).…”

“…The combined organic solvent was washed by brine and dried with MgSO4. The solution was filtered and NMR spectroscopic data matches that reported in the literature 44 .…”

“…This synergistic application of two highlymodular and complexity generating transformations opens up limitless possibilities for rapid synthesis of complex drug-like scaffolds 40,41 . First, as shown in Figure 4 Panel A, to address the limitations of transition-metal catalyzed cross-couplings to access hindered C(sp 3 )-C(sp 3 ) bonds (vide supra), a crosscoupling/reductive protodeboronation sequence was developed [42][43][44][45] . This formal alkyl-alkyl cross-coupling provides a modular approach to access a variety of unfuctionalized C(sp 3 )-C(sp 3 ) bonds.…”

Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists

“…As a result, GPR119 agonists are used for discovery of anti-T2DM agents by lowering the blood glucose level and improving b-cells function. Indeed, numerous synthetic, small molecule GPR119 agonists were revealed by academia and industry to date, and some of which have advanced into clinical trials such as MBX-2982, BMS-903452, LEZ763, ZYG-19 [18][19][20][21][22][23][24][25][26][27][28][29][30] . Despite tremendous endeavours, none of GPR119 agonists were approved to market by FDA up to now.…”

3-((Hetera)cyclobutyl)azetidines, “Stretched” Analogues of Piperidine, Piperazine, and Morpholine: Advanced Building Blocks for Drug Discovery

“…Being inspired by these successful examples, we have designed four novel piperidine, piperazine, and morpholine surrogates, 4 – 7 , which are based on the structural modifications mentioned above (i.e., the use of four-membered rings and incorporation of sulfone and carboxylic acid functionalities) (Figure ). It should be noted that a number of fused, bridged, and spirocyclic analogues of the parent saturated six-membered heterocycles were described in the literature. − These bicyclic ring systems have already proven their value for medicinal chemistry: − some of them can be found in the structures of marketed drugs, for example, boceprevir, gliclazide, and ledipasvir . Nevertheless, all these surrogates were obtained by introducing additional conformational restriction to the piperidine, piperazine, and morpholine rings; in contrast, molecules 4 – 7 are more flexible as compared to the parent structures due to the presence of a rotatable bond.…”