Synthesis, Antitumor Activity, and Docking Analysis of New Pyrido[3′,2′:4,5]furo(thieno)[3,2-d]pyrimidin-8-amines

Abstract

Continuing our research in the field of new heterocyclic compounds, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3′,2′:4,5](furo)thieno[3,2-d]pyrimidines as well as of two new heterocyclic systems: furo[2–e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine. Thus, by refluxing the 8-chloro derivatives of pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidines with various amines, the relevant pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidin-8-amines were obtained. Further, the cyclization of some amines under the action of phosphorus oxychloride led to the formation of new heterorings: imidazo[1,2-c]pyrimidine and pyrimido[1,2-c]pyrimidine. The possible antitumor activity of the newly synthesized compounds was evaluated in vitro. The biological tests evidenced that some of them showed pronounced antitumor activity. A study of the structure–activity relationships revealed that the compound activity depended mostly on the nature of the amine fragments. A docking analysis was also performed for the most active compounds.

3‐Aminothieno[2,3‐b]pyridine‐2‐carboxylate: Effective precursor for microwave‐assisted three components synthesis of new pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐one hybrids

“…They also act as potent and selective vascular endothelial growth factor receptor‐2/kinase insert domain receptor kinase enzyme inhibitors [35], as well as inhibitors of multitarget Ser/Thr kinases [36]. In addition, these hybrids act as good antimicrobial [37,38], antifungal [39], anticancer [40], and antitumor agents [41]. Figure 1 represents some potent bioactive pyridothienopyrimidine hybrids I – III [32,35,38].…”

Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine scaffolds

“…Accordingly, the analogs pyrimido [1,2-c]pyrimidines are a class of 4H-pyrimido [1,6-a] pyrimidines. Sirakanyan et al 19 reported the synthesis of a pentacyclic system, pyranopyridofuro [2,3-e] under either solvent-free microwave irradiation (81-85%) or thermal conditions (51-62%) in diphenyl ether. Tanarro and Gutschow 21 reported the synthesis of 10-benzyl-3,4,9,10,11,12hexahydro-2H-pyrido[4 0 ,3 0 :4,5]thieno [3,2-e]-pyrimido [1,2-c] pyrimidine from ethyl 2-amino-6-benzyl-4,5,6,7-tetrahydrothieno [2,3-c]pyridine-3-carboxylate and evaluated its activity as an inhibitor for acetyl-cholinesterase from EeAChE, hAChE, and hBChE.…”

Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity

“…The pyrimidine moiety has been considered as a privileged structure in medicinal chemistry [ 2 ] and the compounds containing pyrimidine as the core are reported to exhibit diverse types of biological and pharmaceutical activities. For example, pyrimidine derivatives are known as antimicrobial [ 3 , 4 , 5 ], antiviral [ 6 , 7 ], antitumor [ 8 , 9 , 10 ] and antifibrotic compounds [ 11 ].…”