138609-10-6Relevant academic research and scientific papers
Design, synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents
Mohamed, Mohamed M.,Khalil, Ali K.,Abbass, Eslam M.,El-Naggar, Abeer M.
, p. 1441 - 1457 (2017)
A new series of 6-aryl-5-cyano thiouracil derivatives were synthesized. Cyanouracil 1 was condensed with monochloroacetic acid and different aldehydes to give thiazolopyrimidine 2. On the other hand, treatment of cyanouracil 1 with 2-chloro-N-substituted-phenylac etamide afforded 4. Hydrazinolysis of 6 afforded the hydrazino derivatives 7 which upon reaction with different electrophilic reagents such as acetic anhydride, benzoyl chloride, and carbon disulfide yielded pyrimidine derivatives 8–15. Some of the new derivatives were explored for their antimicrobial activities. Compounds 7 and 9 have a promising activity, relatively equipotent to the reference drug. All of the new synthesized compounds were tested in vitro for their antiproliferative activities against HePG-2 and MCF-7 cell lines. Compounds 7, 9, and 2d displayed potent growth inhibitory effect toward the two cell lines more than the standard drug 5-FU. Furthermore, a docking study of the most active compounds was performed with thymidylate synthase enzyme.
Synthesis of Novel Substituted Tetrahydropyrimidine Derivatives and Evaluation of Their Pharmacological and Antimicrobial Activities
Mahmoud, Naglaa F. H.,Ghareeb, Eman A.
, p. 81 - 91 (2019)
Tetrahydropyrimidine derivative 1 was employed as intermediate compound, which in turn was allowed to react with different electrophilic and nucleophilic reagents to synthesize new polyfunctionalized series of substituted pyrimidine-2-thione derivatives. Structures of the newly synthesized compounds have been elucidated by spectroscopic data and elemental analyses. The pharmacological and antimicrobial activities of synthesized products have been evaluated as drug candidates.
Design, synthesis, stereochemical determination, molecular docking study, in silico pre-ADMET prediction and anti-proliferative activities of indole-pyrimidine derivatives as Mcl-1 inhibitors
Lamie, Phoebe F.,Philoppes, John N.
, (2021/09/14)
In this study, fourteen novel indole-pyrimidine hybrids were designed and synthesized. Their chemical structures were confirmed using different spectroscopic techniques (1H NMR, 13C NMR, IR and mass). Their (E) stereochemical configuration was determined theoretically (MM2 property) and experimentally using 2D NMR technique (NOESY experiment). The prepared compounds were subjected to preliminary biological studies as Mcl-1 inhibitors. Most of the compounds exhibited good abilities for targeting Mcl-1 protein, especially, 7d, 7e, 7i and 7k (Ki = 11.19–15.21 nM). These derivatives were further evaluated against Bcl-XL and Bcl-2 proteins. Some compounds were found to have dual Mcl-1/Bcl-XL such as 7i, or Bcl-XL/Bcl-2 inhibitory activity as 7d. The most potent derivatives as Mcl-1 inhibitors were chosen as representative examples for determination of in-vitro anti-proliferative activity against PC-3, K-562 and MDA-MB-231 cell lines. They possessed excellent to good anti-proliferative activities. All of the synthesized compounds were docked into Mcl-1 active site. Drug-likeness properties and in silico pre-ADMET characters were also predicted.
Synthesis and anticonvulsant activity of some 2-(2-{1-[substituted phenyl]ethylidene}hydrazinyl)-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine- 5-carbonitrile
Shaquiquzzaman, Mohammad,Khan, Suroor Ahmad,Amir, Mohammad,Alam, Mohammad Mumtaz
, p. 825 - 831 (2013/02/23)
A series of dihydro-pyrimidine-5-carbonitrile derivatives (3-16) were synthesized and evaluated for their anticonvulsant activity against MES and scPTZ models. Motor impairment screening was carried out by rotarod test method and CNS depressant effect was determined by Porsolt's force swim pool method. Compounds 4 and 9 having p-substituted bromo and m-substituted nitro groups, respectively, were found to be most active showing activity both in MES and scPTZ screen at lower doses of 30 mgkg-1 at 0.5h and 100 mgkg -1 at 4h. In the rotarod motor impairment screen, compound 4 did not show any motor impairment even at the maximum dose of 300 mgkg-1; however, compound 9 showed motor impairment at 300 mgkg-1 dose after 4.0h. The compounds were also tested for their CNS depression effect. The compounds 4 and 9 showed 41.38 and 43.44% increase in immobility time with respect to control. The pharmacophore hypothesis also fits best for compounds 4 and 9.
Synthesis of Pyrimidinone Ring Derivatives
Rashed, N.,Mousaad, A.,Saleh, A.
, p. 393 - 398 (2007/10/02)
Cyclodehydrogenation of the benzalhydrazino derivatives 5 and 6 gave 6-cyano-7-(4-methoxyphenyl)-2-phenyl-5-oxo-1,2,4-triazolopyrimidine (8) and 6-cyano-7-(4-methoxyphenyl)-4-methyl-2-phenyl-5-oxo-1,2,4-triazolopyrimidine (9) respectively.Methylation, acetylation and benzylation of 8 gave the corresponding N-methyl, acetyl and benzyl derivatives 10-12.Methylation of 5 with dimethylsulfate gave 2-benzalhydrazino-5-cyano-3-methyl-6-(4-methoxyphenyl)-3,4-dihydropyrimidin-4-one (6), of which the reaction with acetic anhydride in pyridine afforded the N-acetylbenzalhydrazino derivative 15.The latter was also prepared from acetylation of 5 followed by methylation with iodomethane.Acetylation of 5 with boiling acetic anhydride afforded the diacetyl derivative 16, whereas its benzylation gave the mono-N-benzyl derivative 14.Keywords: fused bicyclic triazolopyrimidinone rings; 1,2,4-triazolopyrimidinones; pyrimidin-4-one; hydrazine; rearrangement
