The structures of 1,4-diaryl-5-trifluoromethyl-1H-1,2,3-triazoles related to J147, a drug for treating Alzheimer's disease

Abstract

J147 [N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3-methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X-ray structures of seven new 1,4-diaryl-5-trifluoromethyl-1H-1,2,3-triazoles, namely 1-(3,4-dimethylphenyl)-4-phenyl-5-trifluoromethyl-1H-1,2,3-triazole (CHFN, 1), 1-(3,4-dimethylphenyl)-4-(3-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (CHFNO, 2), 1-(3,4-dimethylphenyl)-4-(4-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (CHFNO, 3), 1-(2,4-dimethylphenyl)-4-(4-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (CHFNO, 4), 1-[2,4-bis(trifluoromethyl)phenyl]-4-(3-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (CHFNO, 5), 1-(3,4-dimethoxyphenyl)-4-(3,4-dimethoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (CHFNO, 6) and 3-[4-(3,4-dimethoxyphenyl)-5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]phenol (CHFNO, 7), have been determined and compared to that of J147. B3LYP/6-311++G(d,p) calculations have been performed to determine the potential surface and molecular electrostatic potential (MEP) of J147, and to examine the correlation between hydrazone J147 and the 1,2,3-triazoles, both bearing a CF substituent. Using MEPs, it was found that the minimum-energy conformation of 4, which is nearly identical to its X-ray structure, is closely related to one of the J147 seven minima.

Structural Consequences of the 1,2,3‐Triazole as an Amide Bioisostere in Analogues of the Cystic Fibrosis Drugs VX‐809 and VX‐770

“…Thus, while the triazole has similar spatial positioning of the hydrogen bond donating and acceptor groups in comparison to the amide, it should be noted that the hydrogen bond donating and accepting capabilities are reduced in comparison to the amide. Additionally, as has been generally established, [13] the AIM analysis of triazoles 4 and 7 confirms the superior hydrogen bonding acceptor ability of the triazole N3 in comparison to N2 as the N3 atom (À 0.58, À 0.56) in both 4 and 7 has a substantially more negative atomic charge than the N2 atom (À 0.13, À 0.08).…”

“…Synthesis of compounds 1-9: The synthesis and complete characterization (IR, 1 H NMR, 13 C NMR, and HRMS) of compounds 1-9 are reported in our previous work. [2] X-ray data collection and structure refinement: X-ray intensity data was obtained on a Synergy-S diffractometer.…”

PCM-DFT Investigation on the Linear and Nonlinear Optical Properties of Two Triazole Derivatives in Different Solvents

“…The molecular geometry optimization of the title compounds was performed in a diverse set of solvents and in gas phase. The similarities between the X-ray diffraction result obtained by Farrán et al [10] and the optimized molecular structures were analysed calculating the root mean square deviation (RMSD) using the Mercury software [18].…”

“…In this work a study of the solvent media effects on the geometrical and nonlinear optical (NLO) properties of two 1,2,3triazole derivatives, namely: [10] is reported. The solvent media are modelled using the Polarizable Continuum Model (PCM) and the NLO parameters were calculated at DFT/CAM-B3LYP/6-311+G(d) level in gas-phase and in nineteen solvent media.…”

Synthesis, Molecular Docking, and Preliminary Evaluation of 2‐(1,2,3‐Triazoyl)benzaldehydes As Multifunctional Agents for the Treatment of Alzheimer's Disease

“…An interesting group of compounds are the triazoles, that already showed interesting biological activities, such as: neuroprotective effect against oxidative stress and inflammation in a diabetes model, anti‐Alzheimer activity, beta‐secretase inhibition and metal chelating . 1,2,3‐Triazoles stands out as an important class of nitrogen‐based heterocycles being highly studied the synthesis of promising molecules to drugs and new materials .…”