Discovery of New Apoptosis-Inducing Agents for Breast Cancer Based on Ethyl 2-Amino-4,5,6,7-Tetra Hydrobenzo[]Thiophene-3-Carboxylate: Synthesis, In Vitro, and In Vivo Activity Evaluation.

A multicomponent synthesis was empolyed for the synthesis of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[]thiophene-3-carboxylate . An interesting cyclization was obtained when the amino-ester reacted with ethyl isothiocyanate to give the benzo[4,5]thieno[2,3-][1,3]thiazin-4-one . Acylation of the amino-ester with chloroacetyl chloride in DCM and EtN afforded the acylated ester . The amino-ester was cyclized to benzo[4,5]thieno[2,3-]pyrimidin-4(3)-one which was reacted with some alkylating agents leading to alkylation at nitrogen . Hydrazide was utilized as a synthon for the synthesis of the derivatives -. Chloro-thieno[2,3-]pyrimidine was synthesized and reacted with the hydrazine hydrate to afford the hydrazino derivative which was used as a scaffold for getting the derivatives -. Nucleophilic substitution reactions were used for getting the compounds - from chloro-thieno[2,3-]pyrimidine . In the way of anticancer therapeutics development, the requisite compounds were assessed for their cytotoxicity in vitro against MCF-7 and HepG-2 cancer cell lines. Twelve compounds showed an interesting antiproliferative potential with IC from 23.2 to 95.9 µM. The flow cytometric analysis results showed that hit induces the apoptosis in MCF-7 cells with a significant 26.86% reduction in cell viability. The study revealed a significant decrease in the solid tumor mass (26.6%) upon treatment with compound . Moreover, study as an agonist for inhibitors of JAK2 and prediction study determined their binding energies and predicted their physicochemical properties and drug-likeness scores.