70638-54-9

Upstream product

• 123-11-5 4-methoxy-benzaldehyde 
• 17356-08-0 thiourea 
• 105-34-0 methyl 2-cyanoacetate 
• 2826-26-8 2-(4-methoxyphenylmethylene)malononitrile 
• 75129-09-8 4-amino-2-mercapto-6-(4-methoxyphenyl)pyrimidine-5-carbonitrile 
• 50897-91-1 ethyl 2-cyano-3-(4-methoxyphenyl)-acrylate 
• 81585-31-1 4-oxo-6-(4-methoxyphenyl)-2-thioxohexahydropyrimidine-5-carbonitrile 
• 105-56-6 ethyl 2-cyanoacetate 
• 2017-87-0 ethyl (2E)-2-cyano-3-(4-methoxyphenyl)acrylate 

Downstream Products

• 95534-90-0 2-Cyanomethylsulfanyl-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 145434-81-7 3-amino-5H-7-(4-methoxyphenyl)-5-oxo-thiazolo<3,2-a>pyrimidine-2,6-dicarbonitrile 
• 95534-81-9 4-(4-methoxyphenyl)-1-methyl-2-(methylthio)-5-cyano-6-oxo-1,6-dihydropyrimidine 
• 138609-10-6 2-hydrazinyl-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 97693-22-6 4-(4-methoxyphenyl)-2-methylsulfanyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 95534-82-0 1-Benzyl-2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 95534-84-2 4-(4-Methoxy-phenyl)-6-oxo-1-phenethyl-2-phenethylsulfanyl-1,6-dihydro-pyrimidine-5-carbonitrile 
• 138608-95-4 2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 404910-67-4 2-(phenethylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 1203458-10-9 2-(4-nitrobenzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 1448419-72-4 C₁₈H₁₁N₃O₄S 
• 1448419-77-9 C₁₈H₁₁N₃O₄S 
• 1448419-93-9 C₁₉H₁₃N₃O₄S 
• 1448419-99-5 C₁₉H₁₃N₃O₄S 

Relevant academic research and scientific papers

Hydrotalcites as catalyst in suitable multicomponent synthesis of uracil derivatives

Uracil compounds participate in a wide range of biological activities; however, reports on their synthesis using heterogeneous catalysts are scarce. In this work, the multicomponent synthesis of uracil derivatives assisted by layered double hydroxides (LDH) was studied under green chemistry conditions. The incorporation of Ni2+ or Co2+ was successfully performed by co-precipitation method. The yields to uracil derivatives are associated with the presence of weak basic sites and a better interaction of the reagents when the reaction is carried out in solvent-free conditions. The reaction pathway involves the formation of an enone between benzaldehyde and ethyl cyanoacetate, and subsequent reaction with urea, which is assisted by the presence of a basic catalyst. The scope of this synthesis is illustrated with nine examples.

Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies

Two new series of 1,3,4-oxadiazole and coumarin derivatives based on pyrimidine-5-carbonitrile scaffold have been synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds 10c, 10e, 10h-j, 14e-f, 14i and 16 were found to be the most potent and selective inhibitors of COX-2 (IC50 0.041–0.081 μM, SI 139.74–321.95). Eight compounds were further investigated for their in vivo anti-inflammatory activity. The most active derivatives 10c, 10j and 14e displayed superior in vivo anti-inflammatory activity (% edema inhibition 39.3–48.3, 1 h; 58.4–60.5, 2 h; 70.8–83.2, 3 h; 78.9–89.5, 4 h) to the reference drug celecoxib (% edema inhibition 38.0, 1 h; 48.8, 2 h; 58.4, 3 h; 65.4, 4 h). These derivatives were also tested for their ulcerogenic liability, compound 10j showed better safety profile with reference to celecoxib while 10c and 14e exhibited mild lesions. Molecular docking studies of 10c, 10j, and 14e in the COX-2 active site revealed similar orientation and binding interactions as selective COX-2 inhibitors with a higher liability to access the selectivity side pocket.

Design, synthesis and in silico insights of new 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives with potent anticancer and multi-kinase inhibitory activities

Aiming to obtain an efficient anti-proliferative activity, structure- and ligand-based drug design approaches were expanded and utilized to design and refine a small compound library. Subsequently, thirty-two 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives were selected for synthesis based on the characteristic pharmacophoric features required for PI3K and B-Raf oncogenes inhibition. All the synthesized compounds were evaluated for their in vitro anticancer activity. Compounds 17 and 22c displayed an acceptable potent activity according to the DTP-NCI and were further evaluated in the NCI five doses assay. To validate our design, compounds with the highest mean growth inhibition percent were screened against the target PI3Kα and B-RafV600E to confirm their multi-kinase activity. The tested compounds showed promising multi-kinase activity. Compounds 17 and 22c anticancer effectiveness and multi-kinase activity against PI3Kα and B-RafV600E were consolidated by the inhibition of B-RafWT, EGFR and VEGFR-2 with IC50 in the sub-micromolar range. Further investigations on the most potent compounds 17 and 22c were carried out by studying their safety on normal cell line, in silico profiling and predicted ADME characteristics.

Synthesis, antibacterial activities and molecular docking study of thiouracil derivatives containing oxadiazole moiety

A series of novel thiouracil derivatives 9 containing an oxadiazole moiety have been synthesized by structural modification of a lead SecA inhibitor, 2. These compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis. Among them, compounds 9g and 9n exhibited promising antibacterial activities against the tested strains. Compound 9g was also tested for its inhibitory activities against SecA ATPase, and the IC50 value of compound 9g was 19.9 μg/mL, lower than that of compound 2 (20.8 μg/mL). Molecular docking work indicates that compound 9g likely occupies the pocket formed by SecA IRA2 and NBD domain.

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-One Derivatives**

A series of pyrimidine-containing 4H-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vit

Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation

A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI50 ranging from 19 to 100 μM and selectivity ratios ranging between 0.75 and 1.71 at the GI50 level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of ?9.80 to ?11.25 kcal/mol compared to ?12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.

Substituted pyrimidine-containing myricetin derivative as well as preparation method and application thereof

The invention discloses a substituted pyrimidine-containing myricetin derivative as well as a preparation method and application thereof. The general structural formula of the myricetin derivative isshown in the specification, R represents a substituted phenyl group or a substituted aromatic heterocyclic group; n is the number of carbon in a carbon chain and is 2-6; wherein the substituted phenylgroup is on the ortho-, meta-and para- position of a benzene ring and contains C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms; the aromatic heterocyclic groupis thienyl, furyl, pyrrolyl or pyridyl; and substituent groups on substituted aromatic heterocycle are ortho-, meta-and para- positions and contain C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms. The derivative can well inhibit the activity of pathogenic bacteria of plants.

New 2,4-disubstituted-2-thiopyrimidines as VEGFR-2 inhibitors: Design, synthesis, and biological evaluation

A new series of 2,4-disubstituted-2-thiopyrimidines 6a–t, 9a, and 9b was efficiently designed and synthesized as antiangiogenic and cytotoxic agents. Compounds 6j, 6l, and 6d showed IC50 values of 1.23, 3.78, and 3.84 μM, respectively, against the vascular endothelial growth factor receptor-2 (VEGFR-2). Most of the synthesized 2-thiouracils showed antiproliferative activity against the HepG2 cell line (hepatocellular carcinoma) in the micromolar range, for instance, 9b, 6l, 6m, 6n, and 6j displayed IC50 = 7.92, 8.35, 8.51, 9.59, and 13.06 μM, respectively, relative to sorafenib (III; IC50 = 10.99 μM). Also, compounds 6j, 9a, 6m, and 6s (IC50 = 15.21, 16.96, 17.68, and 18.15 μM, respectively) are the most potent compounds against the UO-31 cell line. Further evaluation of the effect of the synthesized candidates on VEGFR-2 in the HepG2 cell line demonstrated that compounds 6j and 6l exhibit VEGFR-2 inhibitory activity of 87% and 84%, respectively, relative to sorafenib (III; 92%). In silico docking of the synthesized hits into the binding site of VEGFR-2 showed their ability to perform the main binding interactions with the key amino acids in the binding site. Studying the in silico predicted ADME (absorption, distribution, metabolism, and excretion) parameters for the synthesized thiouracils demonstrated that they have favorable pharmacokinetic and drug-likeness properties. These results demonstrate that the 2,4-disubstituted thiouracils 6 and 9 have not only favorable antiangiogenic and antiproliferative activity but also satisfy the criteria required for the development of orally bioavailable drugs. Consequently, they represent a biologically active scaffold that should be further optimized for future discovery of potential hits.

Β - secretase enzyme has the function of inhibiting compound, the preparation of the compounds and use thereof

The invention discloses a compound capable of inhibiting beta-secretase, and a preparation method and application thereof. The structure of the compound is shown in a formula I, formula II or formula III as described in the specification. In the formula I, X is S or NH; R1 is selected from hydrogen and nitro group; R2 and R4 are same or different and independently selected from the group consisting of hydrogen, halogen, nitro group and substituted aryl group; R3 is selected from the group consisting of hydrogen, nitro group, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4; R is located at position 2, 3 or 4 of a benzene ring and selected from the group consisting of hydrogen, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4. In the formula II, R is selected from different substituted aryl groups. In the formula III, R is selected from hydrogen or cyano group. Experiments prove that the compound provided by the invention has good beta-secretase inhibitory activity and has wide application values as a beta-secretase inhibitor.

Part III: Novel checkpoint kinase 2 (Chk2) inhibitors; design, synthesis and biological evaluation of pyrimidine-benzimidazole conjugates

Recently a dramatic development of the cancer drug discovery has been shown in the field of targeted cancer therapy. Checkpoint kinase 2 (Chk2) inhibitors offer a promising approach to enhance the effectiveness of cancer chemotherapy. Accordingly, in this study many pyrimidine-benzimidazole conjugates were designed and twelve feasible derivatives were selected to be synthesized to investigate their activity against Chk2 and subjected to study their antitumor activity alone and in combination with the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). The results indicated that the studied compounds inhibited Chk2 activity with high potency (IC50 = 5.56 nM - 46.20 nM). The studied candidates exhibited remarkable antitumor activity against MCF-7 (IG50 = 6.6 μM - 24.9 μM). Compounds 10a-c, 14 and 15 significantly potentiated the activity of the studied genotoxic drugs, whereas, compounds 9b and 20–23 antagonized their activity. Moreover, the combination of compound 10b with cisplatin revealed the best apoptotic effect as well as combination of compound 10b with doxorubicin led to complete arrest of the cell cycle at S phase where more than 40% of cells are in the S phase with no cells at G2/M. Structure-activity relationship was discussed on the basis of molecular modeling study using Molecular modeling Environment program (MOE).