15112-10-4

Upstream product

• 62-53-3 aniline 
• 4921-82-8 1-benzoyl-3-phenylthiourea 
• 103-85-5 monophenylthiourea 
• 105-53-3 diethyl malonate 
• 15837-46-4 6-amino-N₁-phenyl-2-thiouracil 

Downstream Products

• 339593-38-3 6-methoxy-2-(methylthio)-3-phenylpyrimidin-4(3H)-one 
• 1227672-90-3 10-phenyl-9-thioxo-9,10-dihydro-7-oxa-8,10-diazabenzo[a]anthracen-11-one 
• 493016-03-8 2-(3-((4,6-dioxo-3-phenyl-2-thioxo-tetrahydropyrimidin-5(6H)-ylidene)methyl)-1H-indol-1-yl)-N-(furan-2-ylmethyl)acetamide 
• 51325-81-6 5-p-dimethylaminocinnamylidene-1-phenyl-2-thiobarbituric acid 
• 101135-70-0 5-[(E)-3-(6-Hydroxy-4-oxo-1-phenyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-prop-2-en-(Z)-ylidene]-1-phenyl-2-thioxo-dihydro-pyrimidine-4,6-dione 

Relevant academic research and scientific papers

Strategy and validation of a structure-based method for the discovery of selective inhibitors of PAK isoforms and the evaluation of their anti-cancer activity

p21 activated kinase 4 (PAK4), which belongs to the serine/threonine (Ser/Thr) protein kinase family, is a representative member of the PAK family and plays a significant role in multiple processes associated with cancer development. In this study, structure-based virtual screening was performed to discover novel and selective small molecule scaffolds, and a 6-hydroxy-2-mercapto-3-phenylpyrimidin-4(3H)-one-based compound (SPU-106, 14No.) was identified as an effective PAK4 inhibitor. By combining both a molecular docking study and molecular dynamics (MD) simulation strategies, the binding mode was determined in the PAK4 site. The SPU-106 compound could efficiently and selectively bind to the PAK4 kinase domain at an IC50 of 21.36 μM according to the kinase analysis. The designed molecular probe demonstrated that SPU-106 binds to the kinase domain in the C-terminus of PAK4. Further investigation revealed that the SPU-106 had a strong inhibitory effect on the invasion of SGC7901 cells but without any cytotoxicity. The western blot analysis indicated that the compound potently inhibited the PAK4/LIMK1/cofilin and PAK4/SCG10 signaling pathways. Thus, our work shows the successful application of computational strategies for the discovery of selective hits, and SPU-106 may be an effective PAK4 inhibitor for further development as an antitumor agent.

Design and synthesis of novel thiobarbituric acid derivatives targeting both wild-type and BRAF-mutated melanoma cells

A series of novel thio- and seleno-barbituric acid derivatives were synthesized by varying the substituents at N1 and N3 (ethyl, methyl, allyl, and phenyl), and C5 tethered with dienyl and trienyl moieties attached to substituents such as phenyl, 2-furanyl, 2-thiophenyl, 1-naphthyl, and 3-pyridyl. The cytotoxic potential of these derivatives was evaluated by using MTT assay against melanoma cell lines expressing either wild-type (CHL-1) or mutant (UACC 903) BRAF gene. Among all, 2b and 8b were identified as the most potent compounds. Both 2b and 8b inhibited viability of various melanoma cells and induced cell death as evidenced by Live and Dead assay. Western blot analysis showed that they induce PARP cleavage and inhibit anti-apoptotic Bcl-2, Bcl-xL and Survivin in a dose-dependent manner within 24 h of the treatment. Novel thiobarbituric acid analogs also inhibited viability of various other solid tumor cell lines, such as pancreatic, breast, and colon. Overall, 2b, 2d, and 8b emerged as the most effective compounds and make good leads for the development of future therapeutic agents.

Experimental and theoretical investigations on the tautomerism of 1-phenyl-2-thiobarbituric acid and its methylation reaction

In the present study, 1-phenyl-2-thiobarbituric acid (1) was synthesized and the tautomerism of this compound was investigated by FT-IR spectroscopy, X-ray analysis and 1H NMR study as well as quantum chemical calculations. It is found that com

Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis

An efficient process for the discovery of inhibitors of DDAH enzymes, without the requirement for high throughput screening, is described. Physicochemical filtering of a 308,000-compound library according to drug likeness followed by reciprocal nearest neighbour selection produced a representative subset of 35,000 compounds. Virtual screening on a dual processor PC using FlexX, followed by biological screening, identified two hit series. Similarity searches of commercial databases and chemical re-synthesis of pure compounds resulted in SR445 as an inhibitor of Pseudomonas aeruginosa DDAH at 2 μM.

Chemical modification of plant alkaloids. 2. Reaction of cotarnine with barbituric acid derivatives and structure of 5-dihydrocotarnylbarbituric acids

The reaction of barbituric acid and its N-substituted derivatives and 2-thio analogs with cotarnine forms 5-(4-methoxy-6-methyl-5,6,7,8-tetrahydro-2H-1,3-methylenedioxy-[4,5-g]isoquinolinyl-1)barbituric acids, a new class of zwitter-ions, the structure of which was studied by 1H and 13C NMR spectroscopy and mass spectrometry. The prepared compounds exist in solution as stable intermolecular associates and have a complicated H-bonded structure.