70638-55-0

Upstream product

• 17356-08-0 thiourea 
• 105-56-6 ethyl 2-cyanoacetate 
• 100-10-7 4-dimethylamino-benzaldehyde 

Downstream Products

• 95534-73-9 1,3-Diethyl-5-cyano-6-(p-dimethylaminophenyl)uracil 
• 109532-84-5 6-(4-dimethylaminophenyl)-3,4-dihydro-3-(4-nitrobenzyl)-2-(4-nitrobenzylthio)-4-oxo-5-pyrimidinecarbonitrile 
• 95534-86-4 1-Benzyl-2-benzylsulfanyl-4-(4-dimethylamino-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 109532-83-4 1-Butyl-2-butylsulfanyl-4-(4-dimethylamino-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 95534-85-3 4-[4-(dimethylamino)phenyl]-1-methyl-2-(methylthio)-5-cyano-6-oxo-1,6-dihydropyrimidine 
• 1422189-99-8 5-(4-(dimethylamino)phenyl)-2,7-dioxo-2,3-dihydro-7H-thiazolo[3,2-a]pyrimidine-6-carbonitrile 

Relevant academic research and scientific papers

Design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors

Aim: To design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors. Background: Human immunodeficiency virus-1 (HIV-1), a member of retroviridae family, is the primary causative agent of acquired immunodeficiency syndrome (AIDS). Three enzymes viz: inte-grase (IN), reverse transcriptase (RT) and protease play important role in its replication cycle. HIV-1 integrase is responsible for the incorporation of viral DNA into human chromosomal DNA by cata-lyzing two independent reactions, 3′-processing (3′-P) and strand transfer (ST), which are observed as the “point of no-return” in HIV infection. Objective: To develop inhibitors against HIV integrase strand transfer step. Methods: Our previous results indicated that tetrahydro pyrimidine-5-carboxamide derivatives are potent HIV-1 IN inhibitors (unpublished results from our laboratory). Taking clue from above studies and our own experience, we hypothesized 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues (14a to 14n) as inhibitors of HIV-1 Integrase strand transfer. Prototype compound 14 can be viewed as hybrid structure having characteristics of dihy-dropyrimidine derivatives 10-12 and tyrphostin 13. Results: A total of fourteen derivatives of 4-oxo-6-substituted phenyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (14a-14n) were synthesized and evaluated using HIV-1 Integrase Assay Kit (Xpressbio Life Science Products, USA). The percentage inhibition of all compounds was investigated at 10 μM concentration and IC50 value of few highly active compounds was studied. The obtained results were validated by in silico molecular docking study using Glide (maestro version 9.3, Schr?dinger suite) in extra precision (XP) mode. Conclusion: Fourteen 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues were synthesized and evaluated for HIV-1 IN inhibitory activity. Three compounds 14a, 14e, and 14h exhibited significant percentage inhibition of HIV-1 IN. There was good in vitro-in silico correlation. However, none of the derivative was active against HIV-1 and HIV-2 below their cytotoxic concentration. It needs to be seen whether these compounds can be explored further for their anti-HIV or cytotoxic potential.

Design, synthesis, stereochemical determination, molecular docking study, in silico pre-ADMET prediction and anti-proliferative activities of indole-pyrimidine derivatives as Mcl-1 inhibitors

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.

Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma

New anticancer agents are highly needed to overcome cancer cell resistance. A novel series of pyrimidine pyrazoline-anthracene derivatives (PPADs) (4a-t) were designed and synthesised. The anti-liver cancer activity of all compounds was screened in vitro against two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh-7) as well as normal fibroblast cells by resazurin assay. The designed compounds 4a-t showed a broad-spectrum anticancer activity against the two cell lines and their activity was more prominent on cancer compared to normal cells. Compound 4e showed high potency against HepG2 and Huh-7 cell lines ((IC50=5.34 and 6.13 μg/mL, respectively) comparable to that of doxorubicin (DOX) activities. A structure activity relationship (SAR) has been investigated and compounds 4e, 4i, 4m, and 4q were the most promising anticancer agents against tested cell lines. These compounds induced apoptosis in HepG2 and Huh-7 cells through significant activation of caspase 3/7 at all tested concentrations. In conclusion, 4e could be a potent anticancer drug.

Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

A series of 4-(thiazol-2-ylamino)-benzenesulfonamides was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory and cytotoxic activity on human breast cancer cell line MCF-7. Human (h) CA isoforms I, II and IX were included in the study. The new sulfonamides showed excellent inhibition of all three isoforms, with KIs in the range of 0.84-702 nM against hCA I, of 0.41-288 nM against hCA II and of 5.6-29.2 against the tumor-associated hCA IX, a validated anti-tumor target, with a sulfonamide (SLC-0111) in Phase I clinical trials for the treatment of hypoxic, metastatic solid tumors overexpressing CA IX. The new compounds showed micromolar inhibition of growth efficacy against breast cancer MCF-7 cell lines.

Novel dihydropyrimidines and its pyrazole derivatives: Synthesis and pharmacological screening

In the present study, we have synthesized novel dihydropyrimidines (1a-j), their dimethylated adducts (2a-j), and hydrazine derivatives (3a-j) of 2a-j and subsequently their pyrazole derivatives (4a-j). Elemental analysis, IR, 1H NMR and mass s

Synthesis and anti-microbial activity of some pyrimidine derivatives

4-Aryl-5-carboethoxy-6-methyl-1,2,3,4-tetrahydropyrimidin-2-ones have been synthesized from easily available starting materials. The carboethoxy group at the C5-position of the pyrimidine ring is converted to corresponding hydrazide which in turn is condensed with cyclising agents such as aromatic aldehydes, CS2 etc. to give fused heterocycles. The fused heterocycles are then subjected to phenacylation to give N3-phenacylpyrimido-heterocycles in excellent yield. In a slightly modified way, uracil derivatives are condensed with ethyl bromoacetate to give N3-β-ethoxycarbonyl derivatives. The hydrazide derivatives of these N3-β-ethoxycarbonyl derivatives subsequently react with 1,2-diketones to give corresponding pyrimido pyridazine derivatives.

Synthesis of 7-nitro- qnd 7,9-dinitro-4-aryl-3-cyanopyrimidobenzothiazol-2-ones

6-Aryl-5-cyano-2-thiouracils (1) on reaction with 2,4-dinitrochlorobenzene (2A) and picryl chloride (2B) separately gives pyrimidobenzothiazol-2-ones 5A and 5B, respectively.