Series Of Urea Research Articles

Hybrid molecules of carvacrol and benzoyl urea/thiourea with potential applications in agriculture and medicine

Benzoyl phenyl urea, a class of insect growth regulator’s acts by inhibiting chitin synthesis. Carvacrol, a naturally occurring monoterpenoid is an effective antifungal agent. We have structurally modified carvacrol (2-methyl-5-[1-methylethyl] phenol) by introducing benzoylphenyl urea linkage. Two series of benzoylcarvacryl thiourea (BCTU, 4a–f) and benzoylcarvacryl urea (BCU, 5a–f) derivatives were prepared and characterized by elemental analysis, IR, 1H and 13C NMR and Mass spectroscopy. Derivatives 4b, 4d, 4e, 4f and 5d, 5f showed comparable insecticidal activity with the standard BPU lufenuron against Dysdercus koenigii. BCTU derivatives 4c, 4e and BCU 5c showed good antifungal activity against phytopathogenic fungi viz. Magnaporthe grisae, Fusarium oxysporum, Dreschlera oryzae; food spoilage yeasts viz. Debaromyces hansenii, Pichia membranifaciens; and human pathogens viz. Candida albicans and Cryptococcus neoformans. Compounds 5d, 5e and 5f showed potent activity against human pathogens. Moderate and selective activity was observed for other compounds. All the synthesized compounds were non-haemolytic. These compounds have potential application in agriculture and medicine.

Tris-(2-aminoethyl)amine-based tripodal trisindolylureas: new receptors for sulphate

A series of tren-based amide or urea linked tris-indole anion receptors have been synthesised and their anion complexation properties studied in DMSO-d 6/water mixtures.

ChemInform Abstract: Discovery of a Novel Series of Cyclic Urea as Potent CCR5 Antagonists.

AbstractDesign and practical syntheses of a novel class of cyclic urea‐based CCR5‐antagonists demonstrating high antiviral activities against HIV‐1 infection in both HOS and PBL assays are described.

Synthesis and biological evaluation of novel N, N′-disubstituted urea and thiourea derivatives as potential anti-melanoma agents

Two series of urea and thiourea derivatives (1a–11a, 1b–11b) have been synthesized; all the 22 compounds were reported for the first time. Their anti-proliferative activities against the melanoma cell line B16-F10 were evaluated. Among the compounds tested, compound 6b exhibited the most potent activity in melanoma cells growth inhibition (IC50 = 0.33 μM). The bioassay tests showed that anti-proliferative activities of these novel compounds were possibly caused by inhibition of ERK1/2 phosphorylation level. Therefore, compound 6b can be a potential anti-melanoma agent and an inhibitor of ERK1/2 phosphorylation deserving further research.

Discovery of a novel series of cyclic urea as potent CCR5 antagonists

A novel series of cyclic urea-based CCR5 antagonists was designed aiming to resolve instability issue in the fasted simulated intestinal fluid (FSIF) associated with the acyclic urea moiety in 1. This class of CCR5 compounds demonstrated high antiviral activities against HIV-1 infection in both HOS and PBL assays. Further evaluation of these compounds indicated that 16-R not only substantially enhanced its stability, but also exhibited excellent pharmacokinetics properties.

Synthesis and characterization of a novel series of benzenesulfonylurea and thiourea derivatives of 2H-pyran and 2H-pyridine-2-ones as antibacterial, antimycobacterial and antifungal agents

Arylhydrazines reacted with dehydroacetic acid ( 1 ) to give the corresponding 2 H -pyran-2-one hydrazones ( 2 ), which on treatment with hydrazine hydrate afforded the corresponding 1-amino-2 H -pyridin-2-ones ( 3 ). Reaction of 3 with nitrous acid, aromatic aldehyde and substituted benzenesulfonyl chlorides yielded the corresponding 2 H -pyridine-2-one derivatives. A series of urea and thiourea derivatives were also prepared. Some of these compounds have shown significant antibacterial and mild to moderate antimycobacterial and antifungal activities.

An automated, polymer-assisted strategy for the preparation of urea and thiourea derivatives of 15-membered azalides as potential antimalarial chemotherapeutics

A series of 15-membered azalide urea and thiourea derivatives has been synthesized and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (D6), chloroquine/pyremethamine resistant (W2) and multidrug resistant (TM91C235) strains of Plasmodium falciparum. We have developed an effective automated synthetic strategy for the rapid synthesis of urea/thiourea libraries of a macrolide scaffold. Compounds have been synthesized using a solution phase strategy with overall yields of 50–80%. Most of the synthesized compounds had inhibitory effects. The top 10 compounds were 30–65 times more potent than azithromycin, an azalide with antimalarial activity, against all three strains.

Discovery of N-benzyl-N′-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (I): Optimization of the amine portion

Several series of carbamate, urea and carboxamide-based CCR5 antagonists have been discovered via optimizations at the amine portion of lead compound 2. All compounds were evaluated for their antiviral activities. Lead urea 29 showed good pharmacokinetic properties, justifying further development of this series.

Carbamate complexation by urea-based receptors: studies in solution and the solid state

The interactions of a series of urea based neutral hydrogen bond donor anion receptors have been investigated with i) alkylcarbamate anions formed by the reaction of carbon dioxide with primary aliphatic amines and ii) the zwitterionic species formed by the reaction of carbon dioxide with 1,4,5,6-tetrahydropyrimidine. Significant downfield chemical shift changes were observed for the urea NH protons in many cases, consistent with host : anion hydrogen bonding interactions, and thus stabilisation of the carbon dioxide bound species. In the case of the alkylammonium-alkylcarbamate salts, this represents successful competition with electrostatic interactions between the alkylcarbamate and alkylammonium components of the salt. A synchrotron structure of a ternary complex formed by an amide appended diindolylurea, the ammonium carbamate salt formed by 1,3-diaminopropane and CO(2) and 18-crown-6, was elucidated and shows the carbamate group bound by six hydrogen bonds (accepting five and donating one) to the functionalised diindolylurea.

Urea and Thiourea-Functionalized Mesoporous Silica Nanoparticle Catalysts with Enhanced Catalytic Activity for Diels–Alder Reaction

A series of urea- and thiourea-functionalized mesoporous silica nanoparticles (MSN) was synthesized. These materials exhibited a superior catalytic reactivity for Diels–Alder reaction than their homogeneous analogues. The reactivity enhancement was attributed to the site isolation effect induced by the heterogenization of individual catalytic group. The surface hydrogen bonding between the organic catalysts and silanols also improved the catalytic reactivity.

Synthesis and structure–activity relationships of N-benzyl- N-(X-2-hydroxybenzyl)- N′-phenylureas and thioureas as antitumor agents

Two series of novel N-benzyl- N-(X-2-hydroxybenzyl)- N′-phenylureas and thioureas ( 1a– 18a; 1b– 18b) as potential EGFR and HER-2 kinase inhibitors have been discovered. These compounds displayed good EGFR and HER-2 inhibitory activity and the SARs are also been studied. Especially compound 7b demonstrated significant EGFR and HER-2 inhibitory activity (IC 50 = 0.08 μM for EGFR and IC 50 = 0.35 μM for HER-2). Docking simulation was performed to position compound 7b into the EGFR active site to determine the probable binding conformation and antiproliferative assay results indicating that these series of urea and thioureas own high antiproliferative activity against MCF-7. Above all, thiourea 7b would be a potential anticancer agent deserves further research.

QSAR Approach to Correlate TRPV1 Antagonist Activity for a Series of Heteroaromatic Urea

AbstractQuantitative structure‐activity relationship (QSAR) studies have been performed on heterocyclic urea derivatives (n=86) as transient receptor potential vanilloid (TRPV1) antagonists. The whole data set was divided into a training set (81% of the dataset) and a test set (remaining 19%) randomly. Models with genetic function approximation (GFA) and partial least‐squares (PLS) algorithms, developed from the training set were used to assess the predictive potential of the models using test set compounds. Obtained nonlinear and linear QSAR models were developed by using constitutional, chemical and topological descriptors, Num. Rings, Mol. Vol. and PHI to relate to TRPV1 antagonist activity.

Design, synthesis and antimicrobial evaluation of s-triazinyl urea and thiourea derivatives

A series of urea and thiourea derivatives of s-triazine have been developed based on high yielding nucleophilic substitution of 2,4,6-trichloro-1,3,5-triazine by 4-hydroxy coumarin, cyclopropylamine and ammonia at suitable conditions. These were further treated with various substituted aryl isocyanate and aryl isothiocyanate. All the synthesized compounds were evaluated for their antibacterial activities against various Gram-positive and Gram-negative strains of bacteria. A few compounds showed good to superior in vitro antibacterial activity against S.aureus, B.subtilis, E.coli and P.aeruginosa respectively. The new synthesized compounds were characterized using IR, 1 H-NMR and elemental analysis.

Synthesis of pyrrole urea and pyrrole carbonylurea derivatives

A series of urea and carbonylurea distamycin analogs whereby the linker has two NH groups for hydrogen bonding with base pairs of DNA were synthesized. The urea and carbonylurea derivatives are prepared from the in situ generation of pyrrole isocyanate (prepared from compound 3) and acyl isocyanate (compound 9), followed by the reaction with an amine. The synthetic feasibility for the further transformations of the pyrrole urea and pyrrole carbonylurea derivatives was also addressed. The binding abilities of these molecules to calf thymus DNA were evaluated by DNA melting temperature ( T m) analysis.

Tuning urea–phenanthridinium conjugates for DNA/RNA and base pair recognition

A series of novel urea–phenanthridine conjugates was prepared. The variation of linker length connecting two urea–phenanthridinium conjugates regulated their binding mode toward double stranded polynucleotides, consequently controlling selectivity of compounds toward ds-RNA over ds-DNA stabilization as well as selective fluorescence response toward addition of G–C base pair and A–U(T) base pair containing polynucleotides.

Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands

After the CB1 receptor antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Several series of urea, carbamate, amide, sulfonamide and oxalamide derivatives based on 1-benzhydrylpiperazine scaffold were synthesized and tested for CB1 receptor binding affinity. The SAR studies to optimize the CB1 binding affinity led to the potent urea derivatives. After the additional SAR studies to optimize the substituents of diphenyl rings, the combination of 2-chlorophenyl and 4-chlorophenyl turned out to be the most potent scaffold. The CB2 binding affinity assay as well as functional assay was also conducted on these compounds. Herein we wish to introduce several novel CB1 antagonists with IC 50 values less than 100 nM for the CB1 receptor binding.

Synthesis of urea acetates as potential PPARα/γ dual agonists

In the quest for novel PPARα/γ dual agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we designed and synthesized a series of urea acetates as potential PPARα/γ dual agonists. The structure of the target compounds, intermediates were characterized by 1H NMR, HRMS.

Substituted urea/thiourea derived from fluoxetine as potent appetite suppressants

A series of urea and thiourea analogues of fluoxetine (5–17) were synthesized and evaluated for their anorexigenic and antidepressant activities. The related conformationally restrained analogues (20–23) were also prepared for structure–activity relationship (SAR) studies. Many of these derivatives (5, 6, 8, 10, 12, 13, 16, and 23) exhibited significant anorexigenic activity and interestingly were devoid of antidepressant activity, thus emerging as a promising tool for further research work.

Monitoring of Urea and Potassium by Reverse Iontophoresis In Vitro

Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis. (a) After 60-120 min of iontophoresis, linear relationships (p < 0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K(+) closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session. These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.

Novel benzothiazolyl urea and thiourea derivatives with potential cytotoxic and antimicrobial activities

A novel series of benzothiazole urea and thiourea derivatives was synthesized and evaluated for its in vitro cytotoxicity against MCF-7 breast cancer cells. The N1-(benzothiazol-2-yl)-N3-morpholinourea 3 displayed the highest cytotoxic activity in this series. A docked pose of 3 was obtained bound to G-quadruplex of human telomere DNA active site using the Molecular Operating Environment (MOE) module. Moreover, the synthesized compounds were screened for their antimicrobial activity against Mycobacterium tuberculosis H37Rv, E. coli, S. aureus and C. albicans. Again, 3 showed the best activity against M. tuberculosis H37Rv while other compounds were equipotent with ampicillin against S. aureus and E. coli.