Crystal structures of three 6-aryl-2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazoles

Abstract

Three title compounds, namely, 2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]-6-phenylimidazo[2,1-b][1,3,4]thiadiazole, C26H19ClN4S, (I), 2-(4-chlorobenzyl)-6-(4-fluorophenyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazole, C26H18ClFN4S, (II), and 6-(4-bromophenyl)-2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazole, C26H18BrClN4S, (III), have been prepared using a reductive condensation of indole with the corresponding 6-aryl-2-(4-chlorobenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (aryl = phenyl, 4-fluorophenyl or 4-bromophenyl), and their crystal structures have been determined. The asymmetric unit of compound (I) consists of two independent molecules and one of the molecules exhibits disorder of the 4-chlorobenzyl substituent with occupancies 0.6289 (17) and 0.3711 (17). Each type of molecule forms a C(8) chain motif built from N—H...N hydrogen bonds, which for the fully ordered molecule is reinforced by C—H...π interactions. In compound (II), the chlorobenzyl unit is again disordered, with occupancies 0.822 (6) and 0.178 (6), and the molecules form C(8) chains similar to those in (I), reinforced by C—H...π interactions involving only the major disorder component. The chlorobenzyl unit in compound (III) is also disordered with occupancies of 0.839 (5) and 0.161 (5). The molecules are linked by a combination of one N—H...N hydrogen bond and four C—H...π interactions, forming a three-dimensional framework.

The Thiadiazole Ring (THD) Is a Building Block for Potential Inhibitors of the SARS-CoV-2 Main Protease (Mpro): Theoretical Look into the Structure, Reactivity, and Binding Profile of Three 1,3,4-THD Derivatives toward Mpro

“…Despite the abundant literature on 1,3,4-THDs, not enough documentation has been reported on the origin of their structural stability, inherent reactivity, and binding affinity to important enzymes of SARS-CoV-2. As an original contribution to this noteworthy challenge, the present study discusses, in an informed tone, the structure, the reactivity, and the binding affinity of three 1,3,4-THDs (general scheme shown in Figure 1), whose crystal structure was laconically reported by Shamanth and coworkers [13][14][15]. For the sake of clarity, the six rings in compounds 1-3 have been labeled from A to F, with ring D corresponding to the 1,3,4-THD skeleton.…”

Synthesis and crystal structure studies of 5-(trifluoromethyl)-1,3,4-thiadiazol-2(3H)-one at 180 K

“…A series of four biologically active 2-benzamido-5-(4-fluoro-3phenoxyphenyl)-1,3,4-thiadiazoles derivatives were synthesized by Panini et al (2013) and their crystal structures studied to evaluate the effects of systematic variations in the func-tional group attached at the para position of the benzamido ring. Lastly, the crystal structures of three 6-aryl-2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]imidazo [2,1-b][1,3,4]thiadiazoles were reported by Shamanth et al (2020).…”