A Microwave-Enhanced Synthesis and Biological Evaluation of N-Aryl‑5,6,7,8‑tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amines

Abstract

A series of N-aryl-5,6,7,8-tetra-hydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amines were synthesized in moderate to good yield by using a microwave-enhanced conditions. The selected compounds were evaluated for their cytotoxic effects (IC 50 values) on human pulmonary carcinoma (A549), murine BALB/c spontaneous colon adenocarcinoma (CT26) and human hepatocellular liver carcinoma (HepG2) cell lines in vitro. Amongst these compounds, one compound was found to have the better cytotoxic activity with reference to the standard Erlotinib hydrochloride (Tarceva TM) against A549 (IC 50 = 16.06 ± 0.09 μM) and HepG2 (IC 50 = 15.01 ± 0.31 μM) cell lines. Especially, two compounds showed best cytotoxic effects against CT26 (IC 50 = 11.38 ± 0.44 μM) and HepG2 (IC 50 = 8.51 ± 0.52 μM) cell lines, respectively. The preliminary structure-activity relationships were disclosed and the thieno[2,3-d]pyrimidine skeleton could be exploited to potential antitumor agents in the future.

Green catalyst access to thieno [2, 3‐b] pyridines derivatives

“…[17][18][19][20] So far, different synthetic routes towards 3-cyano-2-aminothiophenes have been reported. [21][22][23] However, the presence of both nitrile and secondary amine functions in the same molecule is efficiently used in producing hetero fused thiénopsmidines compounds. [24][25][26] Following to the previously reported method, [27][28][29] we synthesized the starting material 3-cyano-2-aminothiophenes 1a-b, from a One pot modified Gewald reaction of cyclohexanone with activated nitriles that have an active methylene group, and sulfur is particularly simple and rich in possibilities in the presence of morpholine as basic catalyst under reflux ethanol (EtOH) (Table 2).…”

“…[18] The heterocyclic annulated pyrimidine, such as thieno [2, 3-b] pyrimidine derivatives, occupy a special place and have frequently attracted a great deal of interest of chemists researchers. [19] Due to their remarkable applications in different disciplines, identified such as potent anti-cancer, [20] ant diabetic, [21] anti-hypertensive [22] and prevention of cartilage destruction in particular diseases, [23] while they also used in the fabrication of light-emitting diodes in material science, fungicides, [24] herbicides, [25] and insecticides, [26] and have other interesting pharmacological properties (Scheme 1). [27] Owing to their great importance and utility, they encourage many researchers to plan, discover and design new molecular systems [19] which offers some of the greatest hope.…”

Synthesis, Biological, and Molecular Docking Studies on 4,5,6,7-Tetrahydrobenzo[b]thiophene Derivatives and Their Nanoparticles Targeting Colorectal Cancer

“…Taking together, the optimal reduction of CRC incidence, morbidity, and mortality will require concerted efforts to develop novel drug candidates that are capable of eliminating oxidative stress, eradicating bacteria, and/or inhibiting protumorigenic LDHA and PDK1 enzymes. In this regard, thiophene derivatives are extensively explored in the field of drug design and development as antioxidant, antibacterial, and anticancer agents. − In particular, 4,5,6,7-tetra­hydro­benzo­[ b ]­thiophene derivatives have been recognized as promising anticancer agents . Many of them (Figure ) have produced their anti­proliferative effects through targeting metallo­proteinases 2 and 9 (MMP 2 and 9), HIF-1α and the vascular endothelial growth factor receptor, the epidermal growth factor receptor (EGFR), human EGFR-related receptor 2 (HER2), and the colon cancer-related genes, namely, collagen type X α1 (COL10A1) and collagen type XI α1 (COL11A1) …”