Oxazole phosphonic acids as fructose 1,6-bisphosphatase inhibitors with potent glucose-lowering activity

Abstract

Phosphonic acid-containing oxazoles were discovered as potent inhibitors of fructose 1,6-bisphosphatase. Several oxazoles demonstrated significant glucose-lowering activity in rats after intravenous dosing.

Use of Graph Based Descriptors for Determination of Structural Features Causing Modulation of Fructose-1,6-Bisphosphatase

“…The Data set Data of inhibitory concentration (IC 50 ) of 203 compounds, containing oxazole, benzimidazole, purine, desaminobenzimidazole and thiazole rings have been retrieved from literature on the basis of having same assay method ( 3 H-labeled AMP displacement assay) used for activity [16][17][18][19][20]. The inhibitory concentration (IC 50 ) [21] was changed into corresponding pIC 50 and further implicated as the endpoint for QSAR modeling [22].…”

Design and synthesis of diethyl(substituted 2‐benzylbenzofuran‐3‐yl)phosphonates as antioxidant and antimicrobial agents

“…In the last decades, organophosphorus compounds (OPCs) have been widely employed as substrates both in natural products and in synthetic applications because of their ease in reactivity with organic groups usually bonded directly to phosphorus or bonded through a heteroatom . These organic groups exert significant effect on the biocidal activity of the OPCs.…”

The Use of 5-Hydroxymethylfurfural towards Fine Chemicals: Synthesis and Direct Arylation of 5-HMF-Based Oxazoles

“…Amid heterocycles, the oxazole ring is present in different molecules of interest ( Figure 1, 1-3). [16][17][18][19][20][21] The furyl-oxazole scaffold also has presence in chemical or medical literature and its main applications were in the development of molecules with hypoglycemic, [22][23][24] antilipidemic, 23,25,26 antiinflammatory, 27,28 antinoceptive 29 and cardioprotective 30 activities. The usual synthetic routes for oxazole-containing compounds are the oxidative cyclization of amides, α,γ-unsaturated amides, propargylic amides or iminoketones, the annulation of alkynes and nitriles, the ring expansion of ketoaziridines, the Van Leusen reaction between an aldehyde and the commercial reagent tosylmethyl isocyanide (TosMIC), among others.…”

“…In an attempt to replace DMF as solvent, other polar aprotic solvents such as dioxane and 2methyl-THF ( Having in hand these optimized conditions (entry 3), the scope of the reaction was investigated using thirty-three aryl iodides. 69 We obtained compounds containing substituents in the para (5-12, 14-19), meta (20)(21)(22)(23)(24), and ortho (27-31) positions of the aryl ring. Additionally, compounds containing a C2-heteroayl bond (13,(25)(26) and di-or tri-substituted aryl rings (32-35, 37) were also obtained.…”

“…Fluorphen-1-yl)-5-(5-hydroxymethylfuran-2-yl)oxazole (RL240A)(24) The compound was obtained from general procedure B as a yellow solid (61.0 mg, 82% yield) after purification (SiO2, dichloromethane:acetone 9:1). 1 H NMR (CDCl3, 400 MHz): δ = 4.68 (s, 2H, H6"), 6.42 (d, J = 3.5, 1H, H4"), 6.66 (d, J = 3.5, 1H, H3"), 7.16 (tdd, J = 8.4, 2.5 and 1.0, 1H, H4'), 7.39 (s, 1H, H4), 7.44 (td, J = 8.4 and 5.7, 1H, H5'), 7.76 (ddd, J = 9.5, 2.5 and 1.5, 1H, H2'),7.87 (ddd, J = 8.4, 1.5 and 1.0, 1H, H6') 13.…”