Synthesis, CYP 450 evaluation, and docking simulation of novel 4‐aminopyridine and coumarin derivatives

Abstract

Four series of novel compounds based on 4‐aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4‐hydrazide pyridine 1c, seem to be less toxic than 4‐aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l‐arginine amide and 4‐aminopyridine, respectively. These results introduce the synthesized compounds as K+ channel blockers that could be considered for in vivo CNS disease studies.

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

“…Compounds 5b , 5d , and 5e show singlets at δ 5.20, 5.49, 5.45 ppm for –NH 2 ; at δ 7.98, 7.86, 8.08 ppm for C 4 –H; and δ 11.01, 11.09, 11.20 ppm for –NH protons. These data were in agreement and comparable with the reported molecules 5a [ 46 ], and 5c [ 47 ]. Compound 5d show singlet at δ 3.80 ppm for OCH 3 protons; 5e show quartet δ 4.12–4.17 ( J = 21.…”

“…The aromatic carbons appear in the range δ 125.2-146.3 ppm. These data were in good matching and comparable to reported molecules 5a [46], and 5c [47]. Compounds 8 (a-e) show resonance signals in the region δ 142.3-147.2, 163.6-166.1, and 173.3-179.5 ppm for C¼N (triazole ring), COO, and C-SH carbons; and were in good matching with the data of structurally identical reported molecule 3-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one [48,49,50].…”

An efficient strategy for synthesis of new functionalized furo[3,2‐c]pyridin‐4(5H)‐one derivatives under mild conditions

“…The probable reason for these results was the poor stability of intermediate oxime which influences the formation of the target product [13a, 14]. In addition, the unsubstituted nucleophiles, such as commercially available 4‐hydroxy‐6‐methyl‐2 H ‐pyran‐2‐one (5a), the prepared 4‐mercapto‐6‐methyl‐2 H ‐pyran‐2‐one ( 5b ) [15] and 4‐amino‐6‐methyl‐2 H ‐pyran‐2‐one ( 5c ) [16] were also used to react with 2e under above‐described catalytic conditions (Scheme 4). The results showcased that only 3‐(4‐chlorophenyl)‐2,6‐dimethyl‐4 H ‐furo[3,2‐ c ]pyran‐4‐one ( 6a ) was obtained with 73% yield.…”

“…Then, the evaluation of different solvents was conducted in the presence of triethylamine and the results were presented in Table 1 (entries [12][13][14][15][16]. None of them proved to be better than ethanol.…”

Computer-Aided (In Silico) Modeling of Cytochrome P450-Mediated Food–Drug Interactions (FDI)

“…Since this method is more expensive in terms of computational power and time, it is usually implemented for pose optimization in small-scale projects rather than high-throughput screening. For example, IFD was used to evaluate the potential of four novel compounds to inhibit five CYP isozymes [ 77 ]. IFD was also used to explain the different efficiency in the oxidation of aristolochic acid I by various CYP isozymes [ 78 ].…”