Synthesis and Spectral Characterization of New Bis(2‐(pyrimidin‐2‐yl)ethoxy)alkanes and Their Pharmacological Activity

Abstract

The pyrimidine nucleus is an important component of nucleic acids (DNA and RNA) and vitamins (B(2) and folic acid). It is evident from the literature that pyrimidine derivatives possess a wide spectrum of biological activities such as antioxidant, anticancer, antibacterial, and anti-inflammatory activities. On the basis of diverse biological activities, we attempted to synthesize a series of novel bis(2-(pyrimidin-2-yl)ethoxy)alkanes 5a-j in four steps with good yields. 2-Chloropyrimidine (1) was reacted with diethyl malonate in the presence of sodium hydride in dry dimethyl formamide to yield the intermediate diethyl 2-(pyrimidin-2-yl)malonate (2), which on further reaction with sodium chloride and dimethyl sulfoxide yielded ethyl 2-(pyrimidin-2-yl)ethanoate (3). Reduction with sodium borohydride (NaBH(4) ) resulted in the formation of 2-(pyrimidin-2-yl)ethanol (4). This was further reacted with various dibromoalkanes to obtain the title compounds 5a-j. In this current study, we evaluated the antioxidant properties of the title compounds using four in vitro test systems: the 2,2-diphenyl-2-picrylhydrazyl radical-, superoxide radical-, and hydroxyl radical-scavenging assays, and the anti-lipid peroxidation activity test. The title compounds showed promising antioxidant activity when compared to butylated hydroxytoluene. The potency of their antioxidant activity was mainly influenced by the alkyl fragment attached to 2-(pyrimidin-2-yl)ethanol. The ethyl and butyl fragments linked to oxygen led to increased antioxidant activity of the title compounds (i.e., 5b and 5d) in all our in vitro assays.

3-Substituted Benzo[e][1,2,4]triazines: Synthesis and Electronic Effects of the C(3) Substituent

“…The malonate ester 1j was converted to the acetate ester 1y in 89% yield upon heating with sodium chloride in DMSO (Scheme ), following a procedure described for a pyrimidine analogue …”

“…A reaction of 1c with sodium diethyl malonate in DMF, conditions used for an analogous reaction of 2-chloropyrimidine, 65 gave diethyl 2-(benzo [e] [1,2,4]triazin-3-yl)malonate (1j) in a nearly quantitative yield. Similarly, chloride 1c reacted with aniline and morpholine in EtOH affording the desired amines 1k and 1l in 85 and 89% yields, respectively.…”

“…The malonate ester 1j was converted to the acetate ester 1y in 89% yield upon heating with sodium chloride in DMSO (Scheme 13), following a procedure described for a pyrimidine analogue. 65 Molecular and Crystal Structures. Yellow crystals of 3morpholinyl (1l) and 3-phenyl (1p) derivatives suitable for Xray diffraction studies were obtained by slow evaporation of nheptane solutions, while crystals of 3-iodo (1d) and 3dibenzoylamino (1x) derivatives were grown from MeCN solutions.…”

Identification of human presequence protease (hPreP) agonists for the treatment of Alzheimer's disease

“…The chemical structures of the new compounds were confirmed using: IR, 1 H NMR, 13 C NMR spectral data and HRMS, the data for which are presented in the Experimental Protocols section. We observed characteristic IR absorption readings in regions at: 3475–3371 cm −1 and 3342–3330 −1 , for: N–H [37, 38], O–H [39, 40], respectively. In the 1 H NMR spectra of compounds 3a–e & 4a–e , the chemical shifts of aromatic hydrogen’s on the phenyl ring appeared as doublets in region and multiplets of 6.96–7.92 and 6.75–7.94 respectively [41, 42].…”

Synthesis and Structural Study of Some Pyrimidinium Hexafluoridosilicates

“…2-chloropyrimidine, for example, is used as starting compound for the synthesis of pharmaceutical products. 14 Cytosine is a bifunctional molecule (electron-donating and also proton-accepting) which readily forms protonated cationic species. Protonation of cytosine can lead to the formation of hemicytosinium duplex structure in acidic solution which is energetically more favored.…”