Fused and Substituted Pyrimidine Derivatives as Profound Anti-Cancer Agents

Abstract

: The rationale behind drug design is strategic utilization of heterocyclic fragments with specific physicochemical properties to form molecular targeted agents. Among the heterocyclic molecules, pyrimidine has proved to be a privileged pharmacophore for various biological cancer targets. The anticancer potential of small molecules with fused and substituted pyrimidine can be enhanced through bioisosteric replacements and altering their ADME parameters. Despite of several small molecules used in cancer chemotherapy, oncology therapeutics has various limitations. Especially in their routes of administration and their concurrent side effects. Such pernicious effects may be overcome, via selective biological targeting. In this review we have discussed the biological targets to inhibit cancer. Structural activity relationship of fused and substituted pyrimidine was studied. Eco friendly synthetic approaches for pyrimidine derivatives have been discussed. This review will give an insight to scientists and researchers of medicinal chemistry discipline to design small molecules having a pyrimidine scaffold with high anticancer potential.

Functionalized hybrid magnetic catalytic systems on micro- and nanoscale utilized in organic synthesis and degradation of dyes

“…Signicantly, phthalazine-trione derivatives are well-known heterocycles used in the pharmaceutical and biological elds including vaso-relaxants, 190 antifungal, 191 antimicrobial, 192 anti-cancer, 193 and anti-inammatory agents. 194 Besides, benzo [4,5]imidazo [1,2-a]pyrimidines are biologically related fused pyrimidine derivatives, which demonstrate highlighted therapeutic and biological characteristics such as antimicrobial, 195 anti-inammatory, 196 protein kinase inhibitor, 197 and anticancer. 198 In this report, a hybrid magnetic nanocomposite, ZnS/ CuFe 2 O 4 , was applied as a heterogeneous catalyst to synthesize 2,4,5-triaryl-1H-imidazole derivatives through the one-pot condensation of various aromatic aldehydes, benzyl and ammonium acetate, as depicted in Fig.…”

“…Significantly, phthalazine-trione derivatives are well-known heterocycles used in the pharmaceutical and biological fields including vaso-relaxants, 190 antifungal, 191 antimicrobial, 192 anti-cancer, 193 and anti-inflammatory agents. 194 Besides, benzo[4,5]imidazo[1,2- a ]pyrimidines are biologically related fused pyrimidine derivatives, which demonstrate highlighted therapeutic and biological characteristics such as antimicrobial, 195 anti-inflammatory, 196 protein kinase inhibitor, 197 and anticancer. 198 …”

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

“…Pyrimidine/nucleoside molecules are indispensable for cancer cell survival since nucleotide metabolism is a vital pathway for DNA replication, RNA synthesis, and cellular bioenergetics. [42,43] Pyrimidine/nucleoside nuclei have been demonstrated to be useful for the development of novel anticancer agents since their derivatives could exert the anticancer activity by inhibiting protein kinases, the essential enzymes for controlling cell growth, differentiation, migration, and metabolism. [44][45][46] Moreover, pyrimidine/nucleoside derivatives have the potential for reversing ABC-mediated multidrug resistance, and tens of pyrimidine/nucleoside-based agents have already been applied in clinics for the treatment of cancer.…”

Tandem [3+1+1+1] Heterocyclization of α‐Acyl Ketene Dithioacetals with Ammonia and Methanol: Rapid Assembly of Polysubstituted Pyrimidines

“…The privileged pyrimidine frameworks occupy a prominent role in natural products, agrochemicals, pharmaceuticals, supramolecules, and genetic and photophysical materials [1] . Especially their excellent biological and pharmacological activities including antibacterial, [2a,b] antitumor, [2c–f] antimalarial, [2g] anti‐inflammatory, [2h,i] and anticonvulsant [2j,k] etc, have led to the generation of numerous commercialized medicines such asvitamin B1, [3a] nimustine, [3b] voriconazole, [3c] ruxolitinib [3d] (Figure 1). Consequently, the new and efficient synthetic strategies are continuously demanded to acquire pyrimidine cores with rapid diversification.…”