Efficient Synthesis and Biological Evaluation of 2,4‐Diaminothieno[2,3‐d]pyrimidine Derivative

Abstract

Cancer is a main reason for human morbidity and mortality globally. Screening and identifying new anticancer chemical substances is considered as a valid treatment for carcinoma. In our study on synthesis and search towards the development of potential anticancer agents, a series of thieno[2,3-d]pyrimidine derivatives were prepared from the functionalized iminophosphorane via aza-Wittig reaction. Their structures were confirmed by 1 H NMR, 13 C NMR, MS and elemental analysis. The in vitro antitumor activities of compounds were analyzed with CCK8 standard method. It revealed these thieno[2,3-d]pyrimi-dine derivatives were exhibited cytotoxicity against HepG2, HEp-2, and MCF-7 cell lines. The most potent compounds, 5 h and 5 j, were efficacious against HEp-2 cells with IC 50 1.8μmol/L and 0.8μmol/L, respectively. Meanwhile, 5 a, 5 d and 5 h showed broad spectrum of cytotoxicity for HepG2, Hep2 and MCF-7 three different cell lines with IC 50 range of 1.8-87.5μmol/L. Furthermore, we demonstrated that cytotoxicity of 5 j was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent.

A facile synthesis of polysubstituted furo[2,3-d]pyrimidinones and 1,2,4-triazole-fused derivatives

“…The structures of 5a-5e were confirmed based on 1 H NMR, 13 C NMR, mass spectrometry, infrared and elemental analyses. For example, the 1 H NMR spectrum of 5e showed the signals of -OCH 2 at 4.38 ppm as quartets, signals of CH 3 at 1.28, 1.45 and 2.60 ppm as doublet, triplet or singlet.…”

“…11,12 In the course of our work aimed at drug discovery, we recently became interested in the synthesis of a series of new heterocyclic compounds via aza-Wittig reactions. 13,14 Based on our background in poly-substituted furo[2,3-d] pyrimidin-4(3H)-ones, we decided to add a fused 1,2,4-triazole ring, hoping for biologically active compounds. Herein, we report the results of that investigation.…”

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

“…The cytotoxicity of FPS was researched by CCK8 assay according to reported methods ( Hou et al, 2019 ). Hela cells were cultured in DMEM medium containing 10% fetal bovine serum cell culture medium with 5% CO 2 atmosphere at 37°C.…”

Synthesis of fused tetracyclic benzo[4,5]furo[3,2‐d]pyrimidin‐4(3H)‐ones derivatives containing thiadiazole/oxazolidine/triazole/triazinanone moieties

“…Over the past 10 years, considerable interest has been focused on the strategy to design and synthesize new N-heterocycle via aza-Wittig reaction with mild reaction conditions. [11][12][13][14][15] Herein, we report our efforts aiming to the preparation of fused tetracyclic benzo [4,5]furo [3,2-d]pyrimidin-4(3H)-one derivatives containing 1,3,4-thiadiazole/1,2,4-triazole/1,2,4-triazinanone/ oxazolidine moieties via aza-Wittig reactions.…”