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We report an efficient synthesis of 6-substituted imidazo[2,1- b ]thiazoles from 2-aminothiazoles and acetophenones through intramolecular cyclization of in situ generated thiazolium ylides. This one-pot cascade process efficiently forms two C–N bonds and is facilitated by both Cu(OTf)2 /KI and FeCl3 /ZnI2 systems. The method utilizes commercially available starting materials and features mild reaction conditions, tolerance to different functional groups, and ease of operation. The synthetic applicability has further been demonstrated through post-modification of imidazo[2,1- b ]thiazole analogues. [ABSTRACT FROM AUTHOR]

A series of novel 5-oxo-1-(thiazol-2-yl)pyrrolidine-3-carboxylic acids were synthesized via condensation of 2-aminothiazole derivatives and itaconic acid by heating without a solvent. An ester and amide of 1-(benzothiazol-2-yl)-5-oxopyrrolidine-3-carboxylic acid were obtained. 1-(6-Nitrobenzo[d]thiazol-2-yl)- and 1-{5-[(4-nitrophenyl)sulfonyl]thiazol-2-yl}-5-oxopyrrolidine-3-carboxylic acids exhibited bacteriostatic activity against the Gram-positive bacterium Bacillus subtilis ATCC 6633 strain. [ABSTRACT FROM AUTHOR]

A series of new complexes were prepared by ligand (DPTYEDAPIBO) interaction with the following metal chlorides: Ni (II), Cu (II), and Pt (IV), as well as AgNO3 dissolved in ethanol. The ligand (DPTYEDAPIBO) is prepared in three steps: The first step is the preparation of compound (A) which is prepared from the reaction of 2-Aminothiazol in ethanol solvent with Benzil. The second step involves the reaction of benzene-1,2-diamine with (E)-3-(hydroxyamino) butan-2-one to form compound (B). As for the third step, it involves the reaction of the product of the first step, compound (A), with the product of the second step, compound (B), to form the ligand. The structures of the ligand and its complexes are confirmed by FT-IR, 1H-13C-NMR, and UV-Vis spectra, melting points, molar conductivity, elemental analyses (CHN), and magnetic susceptibility measurements. The synthesized complexes are prepared in a (1:1) ratio (M:L) for each of the Ni (II), Cu (II), Ag (I), and Pt (IV) complexes. These measurements suggest octahedral geometry for each of the Ni (II), Cu (II), and Pt (IV) complexes and tetrahedral geometry for the Ag (I) complexes. Each of the ligands and the platinum complex were tested for anticancer activity, and it was discovered that the platinum complex is more effective against breast cancer cells (MCF-7) while having less effect on normal cells (WRL-68). An antioxidant test was also performed for the prepared compounds.

An efficient three‐component synthesis of 4‐aryl‐2‐aminothiazoles was reported. Phenyl‐thioureas reacted with 2‐bromoacetophenones to form 4‐aryl‐2‐aminothiazoles through cyclization, and the subsequent C−N bonding with benzyl/allyl bromides gave the desired disubstituted thiazoles smoothly. The protocol features transition‐metal free, short reaction time, easily available starting materials, good yields and broad substrate scope, showing potential synthetic value for the synthesis of a variety of biologically or pharmaceutically active compounds. [ABSTRACT FROM AUTHOR]

A new series of complexes of the 2-((1E,2E)-1,2-diphenyl-2-(thiazol-2-ylimino)ethylidene)amino)phenol (DPTYEAP) has been synthesized by the reaction of the ligand with metal chlorides of Ni(II), Cu(II), Pt(IV), and AgNO3 in ethanol as a solvent. The ligand was prepared for the two steps. In the first step, compound (A) was synthesized by reacting 2-aminothiazol with benzil in ethanol. Another step is the preparation of the ligand from the reaction of compound (A) with 2-aminophenol. The structures of the ligand and its complexes were confirmed by FTIR, 1H-13C-NMR, UV-Vis spectra, melting points, molar conductivity (C, H, and N), and magnetic susceptibility. The synthesized complexes were prepared in a 1:2 ratio for Ni(II), Cu(II), and Pt(IV) complexes and a 1:1 ratio (M:L) for Ag(I) complexes. The geometric shape of all complexes is octahedral, except for the Ag(I) complex, which is tetrahedral. The antioxidant test for the prepared compounds was carried out. The anticancer test was conducted for each of the ligands and the platinum(IV) complex, and it was found that the platinum complex is more effective against breast cancer cells (MCF-7); thus, it can be used as a potential drug after studying it well.

The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically, the in situ generated α-iodoketone was proposed to be the key active species.

The growing antimicrobial resistance to last-line antimicrobials among Gram-positive pathogens remains a major healthcare emergency worldwide. Therefore, the search for new small molecules targeting multidrug-resistant pathogens remains of great importance. In this paper, we report the synthesis and in vitro antimicrobial activity characterisation of novel thiazole derivatives using representative Gram-negative and Gram-positive strains, including tedizolid/linezolid-resistant S. aureus, as well as emerging fungal pathogens. The 4-substituted thiazoles 3h, and 3j with naphthoquinone-fused thiazole derivative 7 with excellent activity against methicillin and tedizolid/linezolid-resistant S. aureus. Moreover, compounds 3h, 3j and 7 showed favourable activity against vancomycin-resistant E. faecium. Compounds 9f and 14f showed broad-spectrum antifungal activity against drug-resistant Candida strains, while ester 8f showed good activity against Candida auris which was greater than fluconazole. Collectively, these data demonstrate that N-2,5-dimethylphenylthioureido acid derivatives could be further explored as novel scaffolds for the development of antimicrobial candidates targeting Gram-positive bacteria and drug-resistant pathogenic fungi. [ABSTRACT FROM AUTHOR]

• Platinum(II) complexes with 2-aminothiazoles were synthesized and characterized. • DFT calculation. • The interactions of complexes with HSA and CT-DNA were studied. • Cytotoxic and antimicrobial activities of complexes were investigated. The synthesis of new platinum(II) complexes with 2-amino-6-methyl-benzothiazole and 2-amino-6-chlorobenzothiazole as ligands were reported and the proposed structure of the complexes were determined using elemental microanalysis, infrared, 1H and 13C NMR spectroscopy. To verify the suggested structures a computational approach utilizing Density Functional Theory was implemented. The results showed a strong correlation with experimental data, confirming the hypothesized structures of investigated compounds. The interactions of novel platinum(II) complexes with human serum albumin and calf thymus DNA were studied by fluorescence spectroscopy and UV-Vis absorption. The predominantly elevated values of the binding constant, K b , and the Stern-Volmer quenching constant, K SV , stem from the effective attachment of complexes to both HSA and CT-DNA. To establish the mode of interaction, viscosity measurements were conducted. The results showed that complexes are not performing intercalation between the DNA bases, and which probably bind to minor/major grooves. In vitro cytotoxic effect of ligands and platinum(II) complexes was evaluated in the panel of cancer cell lines (mouse mammary carcinoma and colon cancer, and on human mammary carcinoma and colon cancer), and on non-tumor cells, mouse mesenchymal stem cell line using MTT assay. Platinum(II) complex with 2-amino-6-methyl-benzothiazole showed a very good cytotoxic activity mainly by inducing apoptosis. In vitro antimicrobial assay of ligands and complexes was tested against 11 microorganisms using microdilution method and the minimum inhibitory concentration and minimum microbicidal concentration were identified. All tested compounds exhibited moderate antifungal activity and significantly better action on S. aureus ATCC 25,923. [Display omitted] [ABSTRACT FROM AUTHOR]

A convenient and efficient protocol has been developed for the synthesis of thiocyanated aminonitroalkenes and 2,4,5-trisubstituted thiazoles/selenazoles from β-aminonitroalkenes and N ‑thio/selenocyanatosaccharin. This method features simple operation, mild reaction conditions, short reaction time, good functional group compatibility, and metal-free characteristics. The broad applications of polysubstituted thiazoles/selenazoles in organic and medicinal chemistry make this protocol much more practical. [ABSTRACT FROM AUTHOR]

An interaction of 6-aryl-1,2,4-triazine-5-carbonitriles with 2‑amino-4-aryl-substituted thiazoles and oxazoles has been studied. The difference in the reactivity of these aminoheterocycles depending on the presence of an oxygen or a sulfur atom in their composition has been demonstrated. Previously, the 4-aryl-3-hydroxy-2,2′-bipyridines were obtained as products of aza-Diels−Alder reaction between 6-aryl-3-(2-pyridyl)-1,2,4-triazine-5-carbonitriles and 2-amino-4-aryloxazoles. It was shown that the reaction of 6-aryl-1,2,4-triazine-5-carbonitriles with 2-aminothiazoles led to the products of ipso-substitution of cyano group. The aza-Diels−Alder reaction of these compounds with 2,5-norbornadiene gave (2,2′-bi)pyridines with the 2-aminothiazolyl at alpha-position. [ABSTRACT FROM AUTHOR]

2-Aminothiazoles have been synthesized by a one-pot, two-step sequential procedure in solution state which does not involve the isolation of intermediates. It involves α-halogenation of corresponding precursor ketones followed by condensation with substituted thiourea derivatives. All the products were analyzed by IR, NMR, mass spectral techniques and four of them were evaluated crystallographically. One of them crystallizes in the triclinic crystal system with space group P 1 ¯ , while, all the other compounds crystallize in the monoclinic crystal system in two different space groups viz. P21/c and P21/n. The modified 2-aminothiazole core did not show any change in the intermolecular interaction. The N-H...N interaction predominates over other interactions forming centrosymmetric head to head dimer with the neighboring atoms. This feature is observed in all the molecules except N-(4-(4-bromophenyl)-3-(2,5-dimethylphenyl)thiazol-2(3H)-ylidene)-2,5-dimethylaniline. [ABSTRACT FROM AUTHOR]

The growing antimicrobial resistance to last-line antimicrobials among Gram-positive pathogens remains a major healthcare emergency worldwide. Therefore, the search for new small molecules targeting multidrug-resistant pathogens remains of great importance. In this paper, we report the synthesis and in vitro antimicrobial activity characterisation of novel thiazole derivatives using representative Gram-negative and Gram-positive strains, including tedizolid/linezolid-resistant S. aureus, as well as emerging fungal pathogens. The 4-substituted thiazoles 3h, and 3j with naphthoquinone-fused thiazole derivative 7 with excellent activity against methicillin and tedizolid/linezolid-resistant S. aureus. Moreover, compounds 3h, 3j and 7 showed favourable activity against vancomycin-resistant E. faecium. Compounds 9f and 14f showed broad-spectrum antifungal activity against drug-resistant Candida strains, while ester 8f showed good activity against Candida auris which was greater than fluconazole. Collectively, these data demonstrate that N-2,5-dimethylphenylthioureido acid derivatives could be further explored as novel scaffolds for the development of antimicrobial candidates targeting Gram-positive bacteria and drug-resistant pathogenic fungi.

Two polymorphic forms of 1-(4-methylpyridin-2-yl)thiourea (1) and the crystal and molecular structures of the 2-aminothiazoles N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (2) and N-(4-methylpyridin-2-yl)-4-(pyrazin-2-yl)thiazol-2-amine (3), derived from 1 and the respective α-bromoketone via the Hantzsch reaction, are described. Both polymorphic forms 1α (space group P21/c, Z = 4) and 1β (space group P21/n, Z = 8) crystallize in the monoclinic system but exhibit distinctly different intermolecular hydrogen bonding patterns. Compound 2 (orthorhombic, space group Pca21, Z = 8) forms polymeric N–H⋯N hydrogen-bonded zigzag tapes in the polar crystal structure, with a significant twisting between the thiazole and pyridine rings. In contrast, the crystal structure of 3 (monoclinic, space group P21/c, Z = 4) features nearly planar centrosymmetric N–H⋯N hydrogen-bonded dimers, which are laterally joined through long C–H⋯N contacts, affording a π⋯π stacked layered structure. Two polymorphs of 1-(4-methylpyridin-2-yl)thiourea and the crystal and molecular structures of two 2-aminothiazoles, derived from 1-(4-methylpyridin-2-yl)thiourea and α-bromoketones via Hantzsch reaction, are reported. [ABSTRACT FROM AUTHOR]

The synthesis and structural characterization of N-(6-methoxypyridin-3-yl)-4-(pyridin-2-yl)thiazol-2-amine mono-hydrobromide monohydrate (3) and N-(6-methoxypyridin-3-yl)-4-(pyrazin-2-yl)thiazol-2-amine mono-hydrobromide 0.35 methanol solvate (4) are reported. The crystal structures of 3 (monoclinic, space group P21/n, Z = 4) and 4 (monoclinic, space group, C2/c, Z = 8) feature N,4-diheteroaryl 2-aminothiazoles showing similar molecular conformations but different sites of protonation and thus distinctly different intermolecular hydrogen bonding patterns. In 3, Namine–H⋯Br−, N+pyridine–H⋯Owater, and Owater–H⋯Br− hydrogen bonds link protonated N-(6-methoxypyridin-3-yl)-4-(pyridin-2-yl)thiazol-2-amine and water molecules and bromide anions into a three-dimensional hydrogen-bonded network, whereas intermolecular N+methoxypyridine–H⋯Npyrazine hydrogen bonds result in hydrogen-bonded zigzag chains of protonated N-(6-methoxypyridin-3-yl)-4-(pyrazin-2-yl)thiazol-2-amine molecules in 4. [ABSTRACT FROM AUTHOR]

Recently, we described the aminothiazole lead (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine (1), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ∼40 %, and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease-causing prion protein PrP(Sc) . Accordingly, we sought to identify analogues of 1 with improved antiprion potency in ScN2a-cl3 cells while retaining similar or superior properties. Herein we report the discovery of improved lead compounds such as (6-methylpyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)thiazol-2-yl]amine and cyclopropanecarboxylic acid (4-biphenylthiazol-2-yl)amide, which exhibit brain exposure/EC50 ratios at least tenfold greater than that of compound 1.

Abstract Background There is still a need for new alternatives in pharmacological therapy for neglected diseases, as the drugs available show high toxicity and parenteral administration. That is the case for the treatment of leishmaniasis, particularly to the cutaneous clinical form of the disease. In this study, we present the synthesis and biological screening of eight 4-phenyl-1,3-thiazol-2-amines assayed against Leishmania amazonensis. Herein we propose that these compounds are good starting points for the search of new antileishmanial drugs by demonstrating some of the structural aspects which could interfere with the observed activity, as well as suggesting potential macromolecular targets. Methods The compounds were easily synthesized by the methodology of Hantzsch and Weber, had their purities determined by Gas Chromatography-Mass spectrometry and assayed against the promastigote forms of Leishmania amazonensis as well as against two white cell lines (L929 and THP-1) and the monkey’s kidney Vero cells. PrestoBlue® and MTT viability assays were the methodologies applied to measure the antileishmanial and cytotoxic activities, respectively. A molecular modeling target fishing study was performed aiming to propose potential macromolecular targets which could explain the observed biological behavior. Results Four out of the eight compounds tested exhibited important anti-promastigote activity associated with good selectivity indexes when considering Vero cells. For the most promising compound, compound 6, IC50 against promastigotes was 20.78 while SI was 5.69. Compounds 3 (IC50: 46.63 μM; SI: 26.11) and 4 (IC50: 53.12 μM; SI: 4.80) also presented important biological behavior. A target fishing study suggested that S-methyl-5-thioadenosine phosphorylase is a potential target to these compounds, which could be explored to enhance activity and decrease the potential toxic side effects. Conclusions This study shows that 4-phenyl-1,3-thiazol-2-amines could be good scaffolds to the development of new antileishmanial agents. The S-methyl-5-thioadenosine phosphorylase could be one of the macromolecular targets involved in the action.

In the current investigation, two series of 2-amino thiazole derivatives were prepared. The first series involved synthesis of (Z)-3-(thiazol-2-ylimino)indolin-2-one (A1) as Schiff base derivatives of 2-amino thiazole and isatin, then synthesis of compounds A5, A6 and A7 as five membered rings (imidazolidins) by using different amino acids, and synthesis of compounds A3 and A4 as seven membered rings (1,3-oxazepine-di-one) by using maleic and phthalic anhydrides respectively. In the second series, 2-amino thiazole was treated with acetyl acetone to form (2E,4E)-N2,N4-di(thiazol-2-yl)pentane-2,4-diimine (A2) as di-Schiff base derivatives, and finally the preparation of imidazolidin (A8) by using 2 mol of tyrosine and preparation of tetrazole derivative (A9) by using 2 mol of sodium azide. The biological study for the above two series indicated that both gram-negative and gram-positive activities were noticed.

A series of 2-aminothiazoles is prepared in moderate-to-good yields by the direct coupling of ketones and thiourea using I2/dimethyl sulfoxide as a catalytic oxidative system. This method avoids the preparation of lachrymatory and toxic α-haloketones and the use of an acid-binding agent, thus providing a more convenient approach to 2-aminothiazoles compared to the Hantzsch reaction. [ABSTRACT FROM AUTHOR]

Polysubstituted 2-aminothiazoles have been synthesized via a one-pot three-component reaction of α-nitro epoxides, potassium thiocyanate, and primary amines without the need for any additives. This reaction proceeds smoothly in a highly efficient and eco-friendly manner with good to excellent yields. A possible mechanism is also proposed. [ABSTRACT FROM AUTHOR]

Amongst sulfur- and nitrogen-containing heterocyclic compounds, the 2-aminothiazole scaffold is one of the characteristic structures in drug development as this essential revelation has several biological activities abiding it to act as an anticancer, antioxidant, antimicrobial and anti-inflammatory agent, among other things. Additionally, various 2-aminothiazole-based derivatives as medical drugs have been broadly used to remedy different kinds of diseases with high therapeutic influence, which has led to their wide innovations. Owing to their wide scale of biological activities, their structural variations have produced attention amongst medicinal chemists. The present review highlights the recently synthesized 2-aminothiazole-containing compounds in the last thirteen years (2008–2020). The originality of this proposal is based on the synthetic strategies developed to access the novel 2-aminothiazole derivatives (N-substituted, 3-substituted, 4-substituted, multi-substituted, aryl/alkyl substituents or acyl/other substituents). The literature reports many synthetic pathways of these 2-aminothiazoles associated with four different biological activities (anticancer, antioxidant, antimicrobial and anti-inflammatory activities). It is wished that this review will be accommodating for new views in the expedition for rationalistic designs of 2-aminothiazole-based medical synthetic pathways.

The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.

Abstract A novel and efficient reaction has been developed to synthesize a set of substituted 2-aminothiazoles from α-nitroepoxides and ammonium thiocyanate. This reaction could proceed smoothly at mild condition, to afford products for a wide range of substrates with good to excellent yields. A possible mechanism has also been proposed. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A chemoselective thiocyanation of imidazothiazoles and 2-aminothiazoles with use of in situ generated N-thiocyanatosuccinimide (NTS) at room temperature is described. The protocol offers mild reaction conditions and high chemoselectivity for electrophilic substitution in imidazothiazoles over nucleophilic substitution. This method provides metal-free and easy conversion of imidazothiazoles and 2-aminothiazoles into their corresponding C-3 and C-5 thiocyanates, respectively, in good to excellent yield. The present protocol also offers the effective thiocyanation of bifunctional imidazothiazoles containing aliphatic -OH and C(sp2)-H bond functionalities. [ABSTRACT FROM AUTHOR]

In the current investigation, two series of 2-amino thiazole derivatives were prepared. The first series involved synthesis of (Z)-3-(thiazol-2-ylimino)indolin-2-one (A1) as Schiff base derivatives of 2-amino thiazole and isatin, then synthesis of compounds A5, A6 and A7 as five membered rings (imidazolidins) by using different amino acids, and synthesis of compounds A3 and A4 as seven membered rings (1,3-oxazepine-di-one) by using maleic and phthalic anhydrides respectively. In the second series, 2-amino thiazole was treated with acetyl acetone to form (2E,4E)-N2,N4-di(thiazol-2-yl) pentane-2,4-diimine (A2) as di-Schiff base derivatives, and finally the preparation of imidazolidin (A8) by using 2 mol of tyrosine and preparation of tetrazole derivative (A9) by using 2 mol of sodium azide. The biological study for the above two series indicated that both gram-negative and grampositive activities were noticed. [ABSTRACT FROM AUTHOR]

NEt3 was found to be a simple, mild, and efficient catalyst for the synthesis of 2-aminothiazole derivatives from the reaction of different ketones, thiourea, and iodine in EtOH media under mild conditions for the first time. Present methodology offers several advantages, such as simple procedure, shorter reaction times, and milder conditions, and takes place at reflux temperature, with operational simplicity and with excellent yields. [ABSTRACT FROM AUTHOR]

Aminothiazole nuclei and their various derivatives have been long used as precursors for the synthesis of biologically active molecules. As a typical heterocyclic amine, 2-aminothiazole is a cornerstone for the synthesis of many compounds, including sulfur drugs, biocides, fungicides, various types of dyes for synthetic fibers and chemical reaction accelerators and as intermediates in the synthesis of antibiotics, where a large number of 2-aminothiazoles have been substituted with different groups for various pharmaceutical purposes, besides their activity as corrosion inhibitors for mild steel protection as well. The synthetic utility of 2-amino-4-substituted-thiazoles, their reactions and biological activities have been surveyed and are presented in this review. [ABSTRACT FROM AUTHOR]

Substituted 2-aminothiazoles have been synthesized from α -nitro-epoxides, cyanamide, and sodium sulfide through a facile, three-component, and ecofriendly protocol with good to excellent yields. This reaction was achieved at room temperature without any additives. A possible mechanism has also been proposed. [ABSTRACT FROM AUTHOR]

In this work, starch nanoparticles as a green and cheap catalyst were obtained based on the precipitation of amorphous starch in ethanol. It was found that starch nanoparticles are efficient catalyst for the synthesis of 2-aminothiazoles using methylcarbonyl compounds and thiourea as precursors. The use of green and biodegradable nanostarch makes this present methodology quite simple, shorter reaction times and milder conditions, and more convenient and economically viable compared to catalyzed methods reported in the literature. Graphical abstract: [ABSTRACT FROM AUTHOR]

• Newly synthesised the novel acetyl, alkyl substituents of aminothiazole derivative compounds. • The novel compounds were performed antimicrobial activity against food borne pathogens viz., bacillus cereus and candida albicans (MIC-15.53 and 18.58 µgmL−1). • The selected bacillus cereus and candida albicans proteins were analysed molecular docking using autodockVina and the highest binding energy values viz. ,Bacillus cereus - −8.7 kcal/mol and candida albicans - −8.2 kcal/mol. Many derivatives of 2-aminothiazoles are found to have significant biological properties and used as potential antibacterial and antifungal drugs. Therefore new synthetic methodologies for deriving 2-aminothiazole scaffolds are enabled in order to develop enhanced drug activity and therapeutic properties. In this study, a new series of 2-aminothiazole derivatives are synthesized via the cyclocondensation reaction of thiourea with appropriate acid halides followed by condensation with highly functionalized amines to get the amides of biological interest. The products thus obtained are characterized by IR, 1H NMR, 13C NMR and mass spectral data. The synthesized 2-aminothiazole derivatives were screened for antibacterial activity against Bacillus cereus bacterial strains using serial broth dilution methods. In addition the 2-aminothiazole derivatives are screened for their in vitro anti-bacterial and anti-fungal activity through microbial incubatory concentration (MIC) and molecular docking. This in silico technique is used to identify the interaction modes of the derived products with the active site of foodborne pathogen Bacillus cereus and yeast form of fungal pathogen Candida albicans. The study shows good docking scores with acceptable binding interactions. [Display omitted] [ABSTRACT FROM AUTHOR]

Magnetic carbon nanotube-supported imidazolium ionic liquid (CNT-Fe3O4-IL) was synthesized and investigated using various characterization techniques, including Fourier transform infrared and Raman spectroscopies, X-ray diffraction, vibrating sample magnetometry, scanning and transmission electron microscopies, and thermogravimetric and differential thermal analyses. In order to synthesize the CNT-Fe3O4-IL nanocomposites, Fe3O4-decorated multi-walled CNTs were modified with 1-methyl-3-(3-trimethoxysilylpropyl)-1 H-imidazol-3-ium chloride. This catalytic system was found to be a highly stable, active, reusable and solid-phase catalyst for the synthesis of 2-aminothiazoles via the of ketone, thiourea and N-bromosuccinimide under mild conditions. Immobilized magnetic ionic liquid combines the advantages of ionic liquid media with magnetic solid support nanomaterials which enables the application of nanotechnology and in chemical processes. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A convenient and efficient method is described for the synthesis of 2-aminothiazoles by one-pot reaction of ketone and thiourea using chitosan nanoparticles under mild condition. Nanochitosan was used as a biodegradable and green catalyst for this reaction in satisfactory yields. The attractive advantages of the present process include easy isolation of products, milder and cleaner conditions, higher purity and yields and easier work-up procedure. [ABSTRACT FROM AUTHOR]

Tuberculosis is one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extensively drug-resistant strains is a reason for concern. We have previously reported a series of substituted 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides with growth inhibitory activity against Mycobacterium tuberculosis strains and low propensity to be substrate of efflux pumps. Encouraged by these preliminary results, we have undertaken a medicinal chemistry campaign to determine the metabolic fate of these compounds and to delineate a reliable body of Structure–Activity Relationships. Keeping intact the (thiazol-4-yl)isoxazole-3-carboxamide core, as it is deemed to be the pharmacophore of the molecule, we have extensively explored the structural modifications able to confer good activity and avoid rapid clearance. Also, a small set of analogues based on isostere manipulation of the 2-aminothiazole were prepared and tested, with the aim to disclose novel antitubercular chemotypes. These studies, combined, were instrumental in designing improved compounds such as 42g and 42l , escaping metabolic degradation by human liver microsomes and, at the same time, maintaining good antitubercular activity against both drug-susceptible and drug-resistant strains. [Display omitted] • Structure-metabolism relationships of antitubercular 2-aminothiazoles was studied. • An extended SAR investigation of 2-aminothiazoles compounds were carried out. • Information obtained allowed the synthesis of improved analogues. • Compounds 42g and 42l coupled good activity and metabolic stability. • A novel antitubercular chemotypes is disclosed. [ABSTRACT FROM AUTHOR]

A simple protocol to prepare the privileged 2-aminothiazoles promoted by ferrous sulfate heptahydrate via C-N bond formation from vinyl azides and commercially available potassium thiocyanate has been developed. A wide range of vinyl azides are tolerated to afford the expected polysubstituted 2-aminothiazoles in reasonably good yields. The use of the non-toxic substrates and catalyst renders the reaction more environmentally friendly than traditional approaches. [ABSTRACT FROM AUTHOR]

We have developed an effective synthetic method and prepared several 4-hydroxy-1-methyl-2,2-dioxo- N-(1,3-thiazol-2-yl)-1 Н-2λ,1-benzothiazine-3-carboxamides and a few structurally related heterocyclic arylamides. The structural features of one of the substituted thiazolyl-2-amides obtained have been investigated. Compounds with a high analgesic activity have been identified within this group by pharmacological screening. [ABSTRACT FROM AUTHOR]

Abstract: Tuberculosis (TB) is one of the deadliest infectious diseases of all times, and its recent resurgence is a supreme matter of concern. Co-infection with HIV and, in particular, the continuous isolation of new resistant strains, makes the discovery of novel anti-TB agents a strategic priority. The research of novel agents should be driven by the accessibility of the synthetic procedure and, in particular, by the lack of cross-resistance with the drugs already marketed. Moreover, in order to shorten the duration of the therapy, and therefore decrease the rate of resistance, these molecules should be active also against the nonreplicating persistent form (NRP-TB) of the infection. The availability of an in-house small library of compounds prompted us to investigate their anti-TB activity. Two compounds, embodying a 2-aminothiazole scaffold, were found to possess a certain inhibitory activity toward Mycobacterium tuberculosis H37Rv, and therefore a medicinal chemistry campaign was initiated in order to increase the activity of the hit compounds and, especially, construct a plausible body of structure–activity relationships. The potency of the hit compound was successfully improved, and, much more importantly, some of the molecules synthesized were found to be active toward the persistent phenotype, and, also, toward a panel of resistant strains. These findings encourage further investigations around this interesting antitubercular chemotype. [Copyright &y& Elsevier]

Two efficient methods for the amination of 2-halothiazoles are presented here. A first protocol requires a Pd/L system. Several 2-aminothiazoles were synthesized under optimized conditions and isolated in good yields. The first palladium-catalyzed CN coupling reactions between 2-halothiazoles and primary alkylamines are presented. In a second part, ligand-free copper-catalyzed aminations of 2-halothiazoles by alkylamines and aniline in a green solvent have been developed. The protocol is very effective for primary and secondary amines and perfectly tolerates the presence of another halide moiety on the 2-halothiazole. The reaction occurs under the assistance of microwave irradiation, which drastically decreases the reaction time. The reaction leads to the formation of 2-aminothiazoles, key molecules in pharmaceutical research. [ABSTRACT FROM AUTHOR]

Abstract: An efficient one-pot method for the synthesis of 2-aminothiazoles using simple starting materials like isothiocyanates, amidines/guanidines and various halomethylenes is reported. The synthesis of 2-aminothiazoles involves reactions such as nucleophilic addition, S-alkylation and intramolecular nucleophilic substitution in which amines departs as the leaving group. [Copyright &y& Elsevier]

The current review article represents a survey covering the synthetic strategies leading to imidazo[2,1-b]thiazoles since 1980. The review is classified according to nature of starting precursor either 2-aminothiazoles or 2-mercaptothiazoles. [ABSTRACT FROM AUTHOR]

Abstract: The present paper describes an optimized reaction condition for the microwave promoted synthesis of newer 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives, which in turn were prepared in good yield by the treatment of various 2-styryl benzoxazinone derivatives with various 2-aminothiazoles using co-solvent under microwave irradiation. All the compounds were characterized by various spectroscopic techniques and analytical methods. All newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus megaterium, Bacillus subtilis, and Aspergillus niger. [Copyright &y& Elsevier]

Abstract: Substituted 2-aminothiazole derivatives were obtained as a result of N-methylimidazole catalyzed cyclization of α-halo ketone carbonyls with ammonium thiocyanate in water–alcoholic media. The generality of the method has been demonstrated by screening a series of aromatic/heteroaromatic/aliphatic α-halo ketones, α-halo β-diketones, and α-halo β-ketoesters. The developed method is simple, mild, and general route for the preparation of diversely functionalized 2-aminothiazoles in good to moderate yields from readily available starting materials. [Copyright &y& Elsevier]

Abstract: This Letter presents the synthesis and biological evaluation of a collection of 2-aminothiazoles as a novel class of compounds with the capability to reduce the production of PGE2 in HCA-7 human adenocarcinoma cells. A total of 36 analogs were synthesized and assayed for PGE2 reduction, and those with potent cellular activity were counter screened for inhibitory activity against COX-2 in a cell free assay. In general, analogs bearing a 4-phenoxyphenyl substituent in the R2 position were highly active in cells while maintaining negligible COX-2 inhibition. Specifically, compound 5l (R1 =Me, R2 =4-OPh-Ph, R3 =CH(OH)Me) exhibited the most potent cellular PGE2 reducing activity of the entire series (EC50 =90nM) with an IC50 value for COX-2 inhibition of >5μM in vitro. Furthermore, the anti-tumor activity of analog 1a was analyzed in xenograft mouse models exhibiting promising anti-cancer activity. [Copyright &y& Elsevier]

The N-alkylated 2,2,6,6-tetramethylpiperidin-4-ones 3c-f were prepared from the acetal 6a of triacetonamine (3a) by alkylation followed by hydrolysis of the acetal functionality or alternatively from the corresponding secondary alcohol 2,2,6,6-tetramethylpiperidin-4-ol (7a) by N-alkylation and subsequent oxidation to introduce the ketone unit. Direct alkylation of 3a was only possible by using highly reactive halides such as allyl or benzyl bromide with low yields. Treatment of phorone (5) with primary amines 2c-f with an alkyl group greater than methyl did not lead to the desired heterocycles 3c-f since open-chain addition products 8 and 9 were formed instead. Consequently, the reactions of acetone (1) with benzyl- or n-butylamine (2e,f) in the presence of calcium chloride did not generate the corresponding N-alkylated derivatives of 3a. [ABSTRACT FROM AUTHOR]

A simple, efficient, single step and environmentally benign synthesis of 2-aminothiazoles is described in this paper. This green protocol was catalyzed by recyclable solid supported Nafion-H using polyethylene glycol-water solvent system with improved efficiency and reduced waste production. [image omitted] [ABSTRACT FROM AUTHOR]

3-Aryl-2-chloropropanal was obtained by the reaction of arenediazonium chlorides with acrolein in the presence of copper(II) chloride. N-Aryl(2-pyridyl)-5-(R-benzyl)-1,3-thiazole-2-amines were formed in high yield by the reaction of these aldehydes with aryl- and 2-pyridylthioureas. The same compounds were obtained by the reaction of 5-(R-benzyl)-1,3-thiazole-2-amines with aniline. [ABSTRACT FROM AUTHOR]

A simple and facile synthesis of 2-aminothiazoles has been accomplished using molecular iodine catalyzed condensation of bromoketones with thiourea. The advantage of this method is that pure products are formed very rapidly under mild conditions. [ABSTRACT FROM AUTHOR]

Abstract: A highly efficient and facile method has been described for the synthesis of substituted 2-aminothiazoles in water without any added catalyst or co-organic solvent. The reaction was carried out at ambient temperature and the products were obtained in excellent isolated yields. The developed protocol is successfully applied for the preparation of an anti-inflammatory drug, fanetizole. [Copyright &y& Elsevier]