Cyclic Urea Research Articles

ChemInform Abstract: Pd‐Catalyzed C—N Bond Formation with Heteroaromatic Tosylates.

AbstractA protocol for the palladium‐catalyzed amidation of heteroaromatic tosylates is developed.

Computational Thermochemistry of Six Ureas, Imidazolidin-2-one, N,N′-Trimethyleneurea, Benzimidazolinone, Parabanic Acid, Barbital (5,5′-Diethylbarbituric Acid), and 3,4,4′-Trichlorocarbanilide, with an Extension to Related Compounds

A computational study of the structural and thermochemical properties of N-phenyl (open) and N-alkyl (cyclic) ureas, through the use of M05-2X and B3LYP density functional theory calculations has been carried out. The consistency of the literature experimental results has been confirmed, and using mainly isodesmic reactions, the unknown Delta(f)H(0)(g) of the other urea derivatives were estimated. The experimental results together with the theoretical information have permitted the study of the effect of phenyl, p- and m-chlorophenyl, alkyl, and carbonyl substitutions on the thermodynamical stability of urea and its cyclic derivatives. The peculiar behavior of the N-tert-butyl substituent in cyclic ureas has been related to geometric deformations.

Aqueous Ethylenediamine for CO2 Capture

Aqueous ethylenediamine (EDA) has been investigated as a solvent for CO(2) capture from flue gas. EDA can be used at 12 M (mol kg(-1) H(2)O) with an acceptable viscosity of 16 cP (1 cP=10(-3) Pa s) with 0.48 mol CO(2) per equivalent of EDA. Similar to monoethanolamine (MEA), EDA can be used up to 120 degrees C in a stripper without significant thermal degradation. Inhibitor A will effectively eliminate oxidative degradation. Above 120 degrees C, loaded EDA degrades with the production of its cyclic urea and other related compounds. Unlike piperazine, when exposed to oxidative degradation, EDA does not result in excessive foaming. Over much of the loading range, the CO(2) absorption rate with 12 M EDA is comparable to 7 M MEA. However, at typical rich loading, 12 M EDA absorbs CO(2) 2 times slower than 7 M MEA. The capacity of 12 M EDA is 0.72 mol CO(2)/(kg H(2)O+EDA) (for P(CO(2) )=0.5 to 5 kPa at 40 degrees C), which is about double that of MEA. The apparent heat of CO(2) desorption in EDA solution is 84 kJ mol(-1) CO(2); greater than most other amine systems.

ChemInform Abstract: Carbon Dioxide as a Carbonylating Agent in the Synthesis of 2‐Oxazolidinones, 2‐Oxazinones, and Cyclic Ureas: Scope and Limitations.

Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl(2), TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields. This methodology was successfully applied to the synthesis of cyclic ureas up to 7-membered rings from the corresponding diamines.

ChemInform Abstract: Gold(I)‐Catalyzed Amination of Allylic Alcohols with Cyclic Ureas and Related Nucleophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The De Novo Design and Synthesis of Cyclic Urea Inhibitors of Factor Xa: Optimization of the S4 Ligand.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Structure−Activity Relationships in Human Toll-Like Receptor 7-Active Imidazoquinoline Analogues

Engagement of toll-like receptors serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. A structure-activity study was conducted on the TLR7-agonistic imidazoquinolines, starting with 1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as a lead. Modifications of the secondary amine of the C2 ethylaminomethylene side chain are poorly tolerated. The 4-amino group must be retained for activity. Replacement of the imidazole ring of the scaffold with triazole or cyclic urea led to complete loss of activity. A systematic exploration of N(1)-benzyl-C2-alkyl substituents showed a very distinct relationship between alkyl length and TLR7-agonistic potency with the optimal compound bearing a C2-n-butyl group. Transposition of the N(1) and C2 substituents led to the identification of an extremely active TLR7-agonistic compound with an EC(50) value of 8.6 nM. The relative potencies in human TLR7-based primary reporter gene assays were paralleled by interferon-alpha induction activities in whole human blood models.

Pd‐Catalyzed CN Bond Formation with Heteroaromatic Tosylates

A protocol for the palladium(0)-catalyzed amidation of heteroaromatic tosylates was successfully developed. The methodology proved to be effective for a variety of heteroaryl tosylates including the pyridine, pyrimidine, quinoline and quinoxaline ring systems. Successful carbon-nitrogen bond formation with these heteroaryl tosylates could be performed with a wide range of primary amides, oxazolidinones, lactams, anilines and indoles, including one cyclic urea. Moreover, this C-N bond forming reaction provided products with high structural diversity. The coupling reaction was also amenable to scale up applications.

Phosphonium- and Benzotriazolyloxy-Mediated Bond-Forming Reactions and Their Synthetic Applications

Phosphonium and benzotriazolyloxy (and related) intermediates are easily prepared by the reactions of cyclic amides and ureas with (1H-benzotriazol-1-yloxy)triaminophosphonium hexafluorophosphate related reagents. The former intermediates could also be made available using analogous phosphonium reagents prepared in situ or from commercial sources. These intermediates efficiently lead to carbon-nitrogen, carbon-oxygen, carbon-sulfur, and carbon-carbon bond formations through nucleophilic aromatic substitution reactions with various nucleophiles. A new ­reaction involving the generation of phenols in situ from arylboronic acids and oxygen under palladium(0) catalysis or with boronic acids and hydrogen peroxide is reviewed.

Carbon Dioxide as a Carbonylating Agent in the Synthesis of 2-Oxazolidinones, 2-Oxazinones, and Cyclic Ureas: Scope and Limitations

Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl(2), TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields. This methodology was successfully applied to the synthesis of cyclic ureas up to 7-membered rings from the corresponding diamines.

ChemInform Abstract: Selective Synthesis of Eight‐Membered Cyclic Ureas by the [6 + 2] Cycloaddition Reaction of 2‐Vinylazetidines and Electron‐Deficient Isocyanates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Gold(I)-catalyzed amination of allylic alcohols with cyclic ureas and related nucleophiles.

A 1:1 mixture of [P(t-Bu)(2)-o-biphenyl]AuCl and AgSbF(6) catalyzes the intermolecular amination of allylic alcohols with 1-methylimidazolidin-2-one and related nucleophiles that, in the case of gamma-unsubstituted or gamma-methyl-substituted allylic alcohols, occurs with high gamma-regioselectivity and syn-stereoselectivity.

Selective Synthesis of Eight-Membered Cyclic Ureas by the [6 + 2] Cycloaddition Reaction of 2-Vinylazetidines and Electron-Deficient Isocyanates

Selective Synthesis of Eight-Membered Cyclic Ureas by the [6 + 2] Cycloaddition Reaction of 2-Vinylazetidines and Electron-Deficient Isocyanates

Molecular docking and 3D-QSAR studies of HIV-1 protease inhibitors

HIV-1 protease is an obligatory enzyme in the replication process of the HIV virus. The abundance of structural information on HIV-1PR has made the enzyme an attractive target for computer-aided drug design strategies. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV-1PR inhibitors with better efficacy profiles and reduced toxicity. In the present investigation, molecular modeling studies were performed on a series of 54 cyclic urea analogs with symmetric P2/P2' substituents. The binding modes of these inhibitors were determined by docking. The docking results also provided a reliable conformational superimposition scheme for the 3D-QSAR studies. To gain insight into the steric, electrostatic, hydrophobic and hydrogen-bonding properties of these molecules and their influence on the inhibitory activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Two different alignment schemes viz. receptor-based and atom-fit alignment, were used in this study to build the QSAR models. The derived 3D-QSAR models were found to be robust with statistically significant r(2) and r(2)(pred) values and have led to the identification of regions important for steric, hydrophobic and electronic interactions. The predictive ability of the models was assessed on a set of molecules that were not included in the training set. Superimposition of the 3D-contour maps generated from these models onto the active site of enzyme provided additional insight into the structural requirements of these inhibitors. The CoMFA and CoMSIA models were used to design some new inhibitors with improved binding affinity. Pharmacokinetic and toxicity predictions were also carried out for these molecules to gauge their ADME and safety profile. The computational results may open up new avenues for synthesis of potent HIV-1 protease inhibitors.

Synthesis, RNA selective hybridization and high nuclease resistance of an oligonucleotide containing novel bridged nucleic acid with cyclic urea structure

A novel bridged nucleic acid bearing cyclic urea structure was successfully synthesized and introduced into oligonucleotide, displaying attractive characteristics of highly RNA selective hybridization ability and excellent resistance towards nuclease degradation.

Selective Synthesis of Eight-Membered Cyclic Ureas by the [6 + 2] Cycloaddition Reaction of 2-Vinylazetidines and Electron-Deficient Isocyanates

The [6 + 2] cycloaddition reaction of 2-vinylazetidines with electron-deficient isocyanates such as tosyl isocyanate proceeded smoothly in the absence of the catalyst at room temperature, and various cyclic ureas were isolated in good to high yields. Electron-deficient allenes also reacted with the 2-vinylazetidine, and the corresponding azocine derivatives were isolated.

Hydrogen bonding in the urea dimers and adenine–thymine DNA base pair: anharmonic effects in the intermolecular H-bond and intramolecular H-stretching vibrations

The equilibrium structures, binding energies, vibrational harmonic frequencies, and the anharmonic corrections for two different (cyclic and asymmetric) urea dimers and for the adenine–thymine DNA base pair system have been studied using the second-order Moller–Plesset perturbation theory (MP2) method and different density functional theory (DFT) exchange–correlation (XC) functionals (BLYP, B3LYP, PBE, HCTH407, KMLYP, and BH and HLYP) with the D95V, D95V**, and D95V++** basis sets. The widely used a posteriori Boys–Bernardi or counterpoise correction scheme for basis set superposition error (BSSE) has been included in the calculations to take into account the BSSE effects during geometry optimization (on structure), on binding energies and on the different levels of approximation used for calculating the vibrational frequencies. The results obtained with the ab initio MP2 method are compared with those calculated with different DFT XC functionals; and finally the suitability of these DFT XC functionals to describe intermolecular hydrogen bonds as well as harmonic frequencies and the anharmonic corrections is assessed and discussed.

A Practical Approach Towards Synthesis of Octahydroquinazolinone Derivatives in Water

A simple, efficient and green procedure has been developed for the synthesis of octahydroquinazolinone derivatives by Biginelli-type three-component cyclocondensation reactions of cyclic β-diketones, aldehydes and (thio)urea with p-TsOH catalysis in water. Keywords: Octahydroquinazolinone, biginelli reaction, cyclic β-diketones, p-toluenesulfonic acid, synthesis, catalysis

Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors

A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure–activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC 50 = 0.031 μM), lower cytotoxicity (CC 50 >50 μM), and higher selectivity index (SI >1612) compared to its derivatives.

Naphthyridine-based symmetrical and unsymmetrical pyridinium amides in sensing of biotin salt

Two naphthyridine-based receptors have been designed and synthesised for biotin salt. The compounds serve as good hosts for the detection of biotin carboxylate rather than biotin ester. The correct dispositions of the binding groups under an isophthaloyl spacer enable the receptors to bind both the cyclic urea and the carboxylate ends simultaneously with moderate binding constant values. The receptors are effective for the binding of tetrabutylammonium salt of biotin with a concomitant increase in the fluorescence of naphthyridine and show appreciable binding of biotin salt in CH3CN containing 1.2% DMSO. The binding was monitored in CH3CN containing 1.2% DMSO and DMSO using 1H NMR, UV–vis and fluorescence spectroscopic methods.