56311-83-2Relevant academic research and scientific papers
Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABAA receptors
Tikhonova, Tatyana A.,Rassokhina, Irina V.,Kondrakhin, Eugeny A.,Fedosov, Mikhail A.,Bukanova, Julia V.,Rossokhin, Alexey V.,Sharonova, Irina N.,Kovalev, Georgy I.,Zavarzin, Igor V.,Volkova, Yulia A.
, (2020)
Structure–activity relationship studies were conducted in the search for 1,3-thiazole isosteric analogs of imidazopyridine drugs (Zolpidem, Alpidem). Three series of novel γ-aminobutyric acid receptor (GABAAR) ligands belonging to imidazo[2,1-b]thiazoles, imidazo[2,1-b][1,3,4]thiadiazoles, and benzo[d]imidazo[2,1-b]thiazoles were synthesized and characterized as active agents against GABAAR benzodiazepine-binding site. In each of these series, potent compounds were discovered using a radioligand competition binding assay. The functional properties of highest-affinity compounds 28 and 37 as GABAAR positive allosteric modulators (PAMs) were determined by electrophysiological measurements. In vivo studies on zebrafish demonstrated their potential for the further development of anxiolytics. Using the OECD “Fish, Acute Toxicity Test” active compounds were found safe and non-toxic. Structural bases for activity of benzo[d]imidazo[2,1-b]thiazoles were proposed using molecular docking studies. The isosteric replacement of the pyridine nuclei by 1,3-thiazole, 1,3,4-thiadiazole, or 1,3-benzothiazole in the ring-fused imidazole class of GABAAR PAMs was shown to be promising for the development of novel hypnotics, anxiolytics, anticonvulsants, and sedatives drug-candidates.
Synthesis of Imidazo[2,1-b]thiazoles via Copper-Catalyzed A3-Coupling in Batch and Continuous Flow
Rassokhina, Irina V.,Tikhonova, Tatyana A.,Kobylskoy, Sergey G.,Babkin, Igor Yu.,Shirinian, Valerii Z.,Gevorgyan, Vladimir,Zavarzin, Igor V.,Volkova, Yulia A.
, p. 9682 - 9692 (2017/09/23)
A straightforward method for the synthesis of functionalized imidazo[2,1-b]thiazoles starting from benzaldehydes, 2-aminothiazoles, and alkynes under copper(I,II) catalysis was developed. The protocol allows the construction of a variety of aryl-substituted imidazo[2,1-b]benzothiazoles, -[2,1-b]thiazoles, and -[2,1-b][1,3,4]thiadiazoles. The reactions were easy to perform affording most of the desired products in 33-93% yields. The intensification of the process in a continuous-flow reactor increases the products' yields up to quantitative.
