Synthesis, biological evaluation and molecular dynamic simulations of novel Benzofuran-tetrazole derivatives as potential agents against Alzheimer’s disease

Theoretical and Experimental Approaches Aimed at Drug Design Targeting Neurodegenerative Diseases

“…Thus, the new compounds were obtained through a simple metal-free and with high atomic economy MCR, based on Ugi-azide reaction with benzofuran-pyrazole aldehydes 20 previously produced. SAR analysis found that a tertbutyl group in the position R5 of the tetrazole scaffold is essential for a high activity 21 [35]. In an attempt to design a versatile and efficient procedure for the synthesis of highly substituted indeno [ In addition, Kushwaha and co-workers established a preliminary structure-activity relationship (SAR) and designed new pyrazoles containing benzofuran-tetrazole hybrids 21 ( Figure 5).…”

“…Thus, the new compounds were obtained through a simple metal-free and with high atomic economy MCR, based on Ugi-azide reaction with benzofuran-pyrazole aldehydes 20 previously produced. SAR analysis found that a tertbutyl group in the position R5 of the tetrazole scaffold is essential for a high activity 21 [35]. Considering that AD is the most prevalent form of NDD, representing 60-70% of dementia cases around the world in patients over 65 years old, the search for drugs able to reduce its impact has been a subject of study for more than six decades [37].…”

The crystal structure of 5-bromo-2-(1-methyl-1H-tetrazol-5-yl)pyridine, C7H6BrN5

“…Tetrazole, an important five-membered heterocycle, is well employed in medicinal chemistry due to its N-donor characteristics. Tetrazole derivatives have been reported to possess a broad spectrum of biological activities, such as antibacterial [5,6], anticancer [7,8], anti-Alzheimers's disease [9,10], antitubercular [11,12], antimalarial [13,14], and antifungal [15,16] properties. Moreover, many tetrazole-based drugs such as Tedizolid, Cilostazol, Cefamandole and Irbesartan have already been used in clinical practice for the treatment of various diseases.…”

Synthesis of novel N‐aryl‐N‐(1H‐tetrazol‐5‐yl)benzenesulfonamides in water

“…Tetrazoles constitute a very important class of organic compounds playing a significant role in medicinal chemistry, material science and propellants, as ligands in the coordination chemistry [1][2][3][4][5][6][7][8] and synthesis of nitrogencontaining compounds and as bioactive molecules being effective antitumor agents, peptidase inhibitors and antihypertensive drugs. [9][10][11][12][13][14] The classical approaches to tetrazoles, especially aminotetrazoles, are based on the condensation of cyanamides, carbodiimides, aminoiminomethanesulfonic acids, imidoyl chlorides and thioureas with NaN 3 , reaction of NaNO 2 with aminoguanidine, reaction of cyanamides with hydrazoic acid (HN 3 ), isomerization of 1-substituted tetrazoles in the melt state or boiling ethylene glycol, synthesis of 1-arylaminotetrazoles from 1-aryltetrazoles via ring opening by organolithium reagents and NaN 3 at −70 C and reaction of amines with tetrazole containing a leaving group in the 5-position (Scheme 1). [15][16][17][18][19][20] Among the published protocols, most of them have several disadvantages such as the use of moisture-sensitive, expensive/toxic reagents, organic solvents, HN 3 or its in situ generation in the reaction, harsh reaction conditions, tedious work-up, low yields and formation of side products.…”

“…Tetrazoles constitute a very important class of organic compounds playing a significant role in medicinal chemistry, material science and propellants, as ligands in the coordination chemistry [ 1–8 ] and synthesis of nitrogen‐containing compounds and as bioactive molecules being effective antitumor agents, peptidase inhibitors and antihypertensive drugs. [ 9–14 ]…”