Synthesis of Potent Anticancer Thieno[2,3-d]Pyrimidine Derivatives

Abstract

As part of our program to identify novel cytotoxic agents, various series of hexahydrocycloocta [4,5]thieno [2,3-d] pyrimidines and pyrimidin-4-ones substituted by aryl at the C-2 position together with phenylethylamino, substituted amino, hydrazinyl or arylidenhydrazinyl substituents at the C-4 position were synthesised. These compounds were prepared as bioisosteres of gefitinib, an antitumour drug used for the treatment of gastrointestinal stromal tumours. All compounds exhibited antitumour activity against (HCT 116) cell line in vitro. Eight compounds (IC 50 : 3.89, 4.65, 6.63, 6.94, 7.89, 9.53,12.00 and 12.30 µg mL −1 , respectively) exhibited 4.3 to 1.3 fold more potent antitumour activity than imatinib (IC 50 : 16.93 µg mL −1 ). Also, a docking study of the newly synthesised compounds with the active site of CDK2 was described.

Synthesis of Thienopyrimidine Derivatives Starting From Thiophene Ring and Pyrimidine Ring

“…Ivachtchenko et al .11 reported that the amino-thiophene ester (22) was reacted with thiophosgene to generate isothiocyanate (28).…”

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

“…A range of thienopyrimidines 49 , thienotriazones 50 , and thienodiazepinones 51 have been prepared from 2‐aminothiophenes by standard methods (Figure ) . These compounds featured potent antitumor properties, but have not been specifically tested for activity toward the PAFr.…”

Acyl Azides: Versatile Compounds in the Synthesis of Various Heterocycles­

“…However, thiophene-and furan-fused heterocycles are not common. [118][119][120] For the synthesis of furo-fused diazepinones, the monoacid 141 was treated with oxalyl chloride followed by amines to give amides 319. The ester functionality in 319 was first converted into the corresponding acyl azide 321 via 320.…”