Efficient Synthesis of New Thieno[2,3‐d]pyrimidin‐4(3H)‐one Derivatives for Evaluation as Anticancer Agents

Abstract

Thieno[2,3‐d]pyrimidinones were reported to act as potent anticancer agents; in this work, a series of new substituted thieno[2,3‐d]pyrimidinone (6) were synthesized via the aza‐Wittig reaction in satisfactory yields. The structures of these compounds were confirmed by elemental analysis, IR, 1H‐NMR, and mass spectral data, and compound 6h was further analyzed by single crystal X‐ray diffraction. Cytotoxic effect of all the compounds was carried out on human breast and lung cancer cell lines (MCF‐7 and SPC‐A‐1, A459). Compound 6f exhibited the best inhibition activities against A459 with IC50 4.1 μM.

Synthesis of novel heterocyclic fused pyrimidin-4-one derivatives from imino-1,2,3-dithiazoles

“…Following the usual methods, 24 treatment of commercially available ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) (2) in dichloromethane at room temperature afforded 68% of the corresponding iminodithiazole (3) (Scheme 3). The presence of the fused cyclohexane ring avoids unwanted addition of Appel's salt at position C-5 of the thiophene.…”

“…We found that standard methods at room temperature 24 applied to the preparation of 2-Niminodithiazolothiophene derivatives led to a complex mixture of polymeric oily compounds resulting from electrophilic substitution at C-5 of the thiophene ring by N-1 of Appel's salt (2). Nevertheless, condensation of the starting amino ester (8) with one equivalent of Appel's salt (2) in dichloromethane at low temperature (-20 °C) followed by addition of pyridine (2 equiv.)…”

“…The thienopyrimidinone nucleus is known to be a pharmacologically relevant structure in medicinal chemistry and has generated interest from many research groups on account of its useful biological properties. For instance, the thieno [2,3-d]pyrimidinone substructure exhibits anticancer, [1][2][3][4][5] antimalarial 6 and antitubercular 7 activities. Some thieno [2,3-d]pyrimidin-(4)-ones act as selective phosphodiesterase inhibitors for the treatment of inflammatory diseases, 8,9 antagonists of the glutamate receptors 10 whereas others were identified as highly selective SIRT2 inhibitors.…”

Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2+

“…Recently, we have focused on the synthesis of nitrogenous heterocyclic compounds via aza-Wittig reaction, attempting to apply and evaluate their biological activities ( Hu et al, 2010 ; Hu et al, 2014 ; Wang et al, 2016a ; Wang et al, 2016b ; Li et al, 2016 ; Liu M.-G. et al, 2019 ; Liu N. et al, 2019 ; Gao et al, 2019 ; Liu et al, 2021 ). Herein, we designed a Schiff base bearing furopyrimidinone scaffold ( FPS ) synthesized from 2-hydroxy-benzaldehyde with furo [2,3-d]-pyrimidine-5-carbohydrazide ( Scheme 1 ), and fluorescence analysis showed that FPS displayed highly selective recognition Zn 2+ with no apparent interference from other metal ions in MeOH solution and its applications in cell imaging and detection Cu 2+ ions.…”

Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

“…Therefore, investigation for the preparation of thieno[2,3-d]pyrimidin-4(3 H )-ones has intrigued researchers to make numerous efforts in synthetic methodology [21,22,23,24,25]. In the course of searching for new cholinesterase inhibitors based on evodiamine, we reported a new one-pot protocol for the straightforward synthesis of rutaecarpine and its analogs from isatoic anhydride and 4,9-dihydro-3 H -pyrido[3,4- b ]indole [26,27].…”