65119-75-7

Upstream product

• 111633-95-5 5-p-tolyl-hydantoic acid ethyl ester 
• 624-31-7 4-tolyl iodide 
• 461-72-3 2,4-imidazolidinedione 
• 106-49-0 p-toluidine 
• 2949-22-6 Glycine ethyl ester isocyanate 
• 590-28-3 potassium cyanate 
• 16634-82-5 N-(p-tolyl)-2-chloroacetamide 
• 622-51-5 p-tolylurea 
• 56-40-6 glycine 
• 34582-49-5 5-p-Tolyl-hydantoinsaeure 

Downstream Products

• 101601-57-4 5-(2-nitro-benzylidene)-3-p-tolyl-imidazolidine-2,4-dione 
• 1387637-36-6 C₁₃H₁₅N₃O₂ 
• 1388265-68-6 C₃₄H₃₄FN₉O₄S 

Relevant academic research and scientific papers

Cu-catalyzed N-3-Arylation of Hydantoins Using Diaryliodonium Salts

A general Cu-catalyzed, regioselective method for the N-3-arylation of hydantoins is described. The protocol utilizes aryl(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence of triethylamine and a catalytic amount of a simple Cu-salt. The method is compatible with structurally diverse hydantoins and operates well with neutral aryl groups or aryl groups bearing weakly donating/withdrawing elements. It is also applicable for the rapid diversification of pharmaceutically relevant hydantoins.

Structural optimization of non-nucleoside DNA methyltransferase inhibitor as anti-cancer agent

Inhibition of DNA methyltransferase 1 (DNMT1) can reverse the malignant behavior of cancer cells by restoring expression of aberrantly silenced genes that are required for differentiation, senescence, and apoptosis. Clinically used DNMT1 inhibitors decitabine and azacitidine inhibit their target by covalent trapping after incorporation into DNA as azacytidine analogs. These nucleoside compounds are prone to rapid enzymatic inactivation in blood, posing challenges to the development of purely epigenetic dosing schedules. Non-nucleoside compounds that suppress expression or function of DNMT1 may overcome this problem. Using a high-throughput PCR-based site specific chromatin condensation assay, we identified a compound that reactivated Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) in myeloma cells and suppressed expression of DNMT1 from a library of 5120 chemically diverse small molecules. Lead optimization was performed to generate 26 new analogs with lung cancer proliferation and DNMT1 expression as activity readout. Two of the new derivatives showed 2 fold improvement of growth inhibiting potency and also decreased DNMT1 protein levels in lung cancer cells.

A New Method of Synthesis of 3-Monosubstituted-2-thiohydantoins and -Hydantoins

A new method of synthesis of 3-monosubstituted derivatives of 2-thiohydantoin and hydantoin in reaction of isothiocyanate or isocyanate glycin ethyl ester with primary aliphatic and aromatic amines has been described. Crude products were obtained with high yield and purity. The structure of these compounds was confirmed by spectral methods. Key words: 2-thiohydantoin, hydantoin, isothiocyanate glycin ethyl ester, isocyanate glycin ethyl ester

MECHANISM OF BASE-CATALYZED CYCLIZATION OF ETHYL N-(SUBSTITUTED AMINOCARBONYL)GLYCINATES

The cyclization rate constants have been measured of substituted ethyl N-(phenylaminocarbonyl)-, N-(alkylaminocarbonyl)-, and N-(phenylaminothiocarbonyl)glycinates RNHCXNHCH2CO2C2H5 (X=O,S).Logarithms of these constants increase with decreasing basicity of the amines down to the value of pKa(RNH2) = 5.5.The rate-limiting step of the reaction is formation of the tetrahedral intermediate.With ethyl N-(phenylaminocarbonyl)glycinates (whose pKa(RNH2) values are higher) this dependence, on the contrary, slightly decreases, and the acid-catalyzed splitting off of ethoxy group from the cyclic intermediate becomes rate-li miting.The cyclization rate of a series of ethyl N-(phenylaminothiocarbonyl)glycinates is practically independent of the pKa(RNH2) values, the change in the rate limiting step would take place at pH about 9.