Synthesis and biological activity of fused furo[2,3-d]pyrimidinone derivatives as analgesic and antitumor agents

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

“…To further extend the method for preparation of diverse tetracyclic pyrimidinones, functionalized iminophosphoranes 10, converted using compounds 8b reaction with triphenylphosphine, C 2 Cl 6 , and N(C 2 H 5 ) 3 , reacted with phenyl isocyanate to produce carbodiimide intermediate, and then intramolecular cyclization easily gives new fused tetracyclic benzo [4,5] The intermediates 4a and 4b can be obtained according to a published method. [3] To a solution of iminophosphorane (4.65 g) and carbon disulfide (10 mL) in anhydrous CH 2 Cl 2 and CH 3 CN (20 mL, v/v = 1:1) was refluxed for 30 hours at 40 C-45 C, and then removed triphenylphosphine sulfide, further reaction with equimolar hydrazine hydrate or amino-ethanol in 20 mL ethanol to give 4a and 4b, respectively, which was used directly without further purification. To a mixture of 4a (2 mmol) 5 mmol Ph 3 P (1.31 g) and 5 mmol C 2 Cl 6 (1.20 g) in dry CH 3 CN (15 mL) was added dropwise N(C 2 H 5 ) 3 (1.4 mL, 10 mmol), after the reaction was over (monitored with TLC), n-C 4 H 9 NCO (2 mmol) was added, and then stirred 4 hours at 25 C-30 C to give fused tetracyclic pyrimidinone containing 1,3,4-thia-diazole 5a.…”

“…The intermediates 4a and 4b can be obtained according to a published method. [ 3 ] To a solution of iminophosphorane (4.65 g) and carbon disulfide (10 mL) in anhydrous CH 2 Cl 2 and CH 3 CN (20 mL, v/v = 1:1) was refluxed for 30 hours at 40°C‐45°C, and then removed triphenylphosphine sulfide, further reaction with equimolar hydrazine hydrate or amino‐ethanol in 20 mL ethanol to give 4a and 4b , respectively, which was used directly without further purification.…”

“…Some of them show anti‐inflammatory, good analgesic, and anti‐microbial activities. [ 3,4 ] In addition, furopyrimidine as a fused ring with other heterocyclic moieties show prime antitumor activity through inhibition of EGFR tyrosine kinase enzyme. [ 5 ] On the other hand, several heterocycle containing triazinanone, thiadiazole, oxazolidine, and triazole have a wide range of medicinal properties, for example, insecticidal, bactericidal, fungicidal, anti‐inflammatory, and antitumor agents.…”

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

“…Heterocycles containing the furopyrimidinone system are considered templates for drug design and discovery because of their remarkable biological activities. Thus, some of them have shown anti-inflammatory, 1 antiviral, 2 analgesic, 3 antiproliferative, 4 and antimicrobial 5 activities. Heterocycles containing the 1,2,4-triazole nucleus also possess diverse biological activities such as fungicidal, bactericidal, insecticidal, antitumor and as anti-inflammatory agents.…”

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

“…And that, some of fused pyrimidines, for example GDC‐0941 and GNE‐493 also possess thienopyrimidine scaffold, is under Phase II clinical trials. In recent years, we have focused on developing expedient aza ‐Wittig reactions of functionalized iminophosphoranes methods for a straight forward library synthetic route to fused pyrimidine derivatives aimed at the development new potent antitumor agents . Previously, we have synthesized various 2,4‐diaminofuro[2,3‐d]pyramiddines which showed remarkable potent anticancer activity…”