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The C−N functionalization of thiazole appendant aryl halides using copper mediated transformation has the potential as a strategy for late‐stage Goldberg coupling of carboxamide and heteroaryl halide. The C−N coupling of thiazole scaffold in the presence of copper is highly challenging. The current work presents the C−N coupling of various amides with thiazole derivatives that afforded variety of amide products. The 4‐(4‐bromo‐phenyl)‐2‐methylthiazole, 4‐(4‐bromophenyl)‐2‐pyridiythiazole and 4‐(3‐bromophenyl)‐2‐methylthiazole reacted with aliphatic, aromatic and cyclic amides smoothly in the presence of stoichiometric amount of copper iodide and N,N'‐DMEDA resulting in C−N bond formation in high yields. The reaction optimization attest to the requirement of stoichiometric amount of copper for the thiazolyl aryl bromide. While the corresponding oxazole can easily undergo the amide coupling employing only catalytic amount of copper. [ABSTRACT FROM AUTHOR]

In the search for new fluorescent triphenylamine (TP) derivatives, we studied the influence of the position and substitution of diverse heterocyclic substituents. A library of 10 fluorescent triphenylamines bearing either oxazoles or thiazoles and pyridiniums, substituted at different positions has been developed. The approach is based on a convergent C−H activation reaction between pyridine‐oxazoles or pyridine‐thiazoles and di‐iodo triphenylamine. We showed that the nature and substitution pattern of the 5‐membered‐ (oxazole, thiazole) or 6‐membered heterocycle (pyridine) has a strong influence on their fluorescence properties and on their localization in living cells as they stain either the nucleus or mitochondria. [ABSTRACT FROM AUTHOR]

A potent antiepileptic drug was developed by synthesizing a set of novel thiazoles substituted oxazole derivatives using multi-step synthesis. FT-IR, 1H-NMR, Mass spectroscopy, and elemental analyses are employed to confirm the structure of compounds. Molinspiration online tool was used to predict the molecular properties and molecular docking was employed to predict the antiepileptic potency of the title analogs. MES and scPTZ tests were employed to determine the antiepileptic potency of thirteen prepared novel thiazole substituted oxazole derivatives. In addition, the neurotoxicity of the compounds was also estimated using the rotarod test. Entire tested derivatives displayed varying degrees of antiepileptic and neurotoxicity potency. The pharmacological potency of prepared derivatives was compared with their chemical structures. Among fifteen tested title compounds the potent compound of this series was found to be 4-(4-(2-(4-chlorobenzylideneamino)thiazol-4-yl)benzylidene)-2-methyloxazol-5(4H)-one BTBO3 which may act as a lead molecule to find potent and safer antiepileptic drug. [ABSTRACT FROM AUTHOR]

The current gathering is intended for examining the synthesis of a chemical moiety, oxazole. Oxazole is a vital heterocycle moiety, devouring effective healing action with three loci for substitution. Oxazole nucleus comprises one pyridine type nitrogen and a single oxygen atom in a heterocyclic system that has been inspected in the expansion of novel molecules relying upon various substitutions with encouraging pharmaceutical possessions. This review focuses on 47 synthetic schemes involving radiation, metal-mediated, one-pot, and other approaches for oxazoles and their derivatives, which headed to the improvement of new-fangled man-made methods along with modifications of standard approaches. These therapeutically active oxazole conjugates have fascinated plentiful investigators globally to scout and synthesize this attractive skeleton for clinically innovative latent beneficial intermediates. [ABSTRACT FROM AUTHOR]

Non-steroid biologically active heterocyclic compounds (Z)-N'-(4-(2-(4-chlorophenyl)benzo[d]thiazol-3(2H)-yl) oxazol-2-yl)-N-(4-substituted phenylimino)-3-substituted-2,3-dihydrobenzo[d]oxazole-2-carboxamidine (4a-4h) and (Z)-N'- (4-(2-(4-chlorophenyl)benzo[d]thiazol-3(2H)-yl)thiazol-2-yl)-N- (4-substituted phenylimino) -3-substituted-2-hydrobenzo[d] thiazole-2-carboxamidine (4a'-4h') have been synthesized, tested for their antimicrobial inhibiting potential and compared with standard drugs Miconazole (antifungal) and Imipenem (antibacterial). Compound 4e' is more potentially active than other compounds and standard drugs. The structure configuration of newly synthesized compounds has been determined by elemental analysis and various spectroscopic (IR, 1H and 13CNMR and GCMS) techniques. [ABSTRACT FROM AUTHOR]

The reactivity of α-azidochalcones has been explored for the preparation of highly substituted oxazoles via a 2H-azirine intermediate. The azidochalcones, when treated with potassium thiocyanate in the presence of potassium persulfate, lead to 2,4,5-trisubstituted oxazoles in good yields. Incidentally, 2-aminothiazoles are the products when ferric nitrate is employed instead of persulfate in the above reaction.

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.

Two new spiroindolinonaphthoxazine derivatives with an electron-accepting styrylquinolizinium or styrylcoralyne unit, respectively, were synthesized, and the influence of such an arylvinyl substituent on the chemical and photochemical properties of the compounds was investigated. Specifically, these spirooxazines turned out to be resistant towards the photoinduced merocyanine formation, and the irradiation with light mainly led to photodegradation of the substrates. However, it was shown by colorimetric and fluorimetric screening assays as well as by detailed NMR spectroscopic and mass spectrometric studies that the addition of particular metal ions (Cu2+, Fe3+, and to a certain extent Hg2+) initially induced a ring-opening reaction that was irreversibly followed by a fast ring closure–deprotonation–oxidation sequence to give styryl-substituted naphthoxazole derivatives as the products quantitatively. For the quinolizinium-substituted spirooxazine derivative, the formation of the respective oxidation product caused the development of a broad absorption band between 425 nm and 500 nm and a new emission band at λfl = 628 nm, so that it may be employed as a selective chemosensor or chemodosimeter for the colorimetric and fluorimetric detection of Cu2+ and Fe3+.

We herein report a modified approach for the synthesis of some pharmacologically relevant oxazole derivatives linked with amides under mild conditions. The utilization of polymer-supported triphenylphosphine (poly-TPP) as a phosphine ligand for generating the key iminophosphorane intermediate was found to be vital for achieving the synthesis of oxazole in room temperature. This alternative approach relying on the cyclization reaction of readily available phenacyl azide and phenyl isothiocyanate rendered the oxazole derivative 3a in excellent yield. This methodology has been applied for the synthesis of a more decorated oxazole derivative 3b having ester functionality and was further converted to different amides under microwave irradiation in good to excellent yields in the later stage.

Background Since 1 September 2016, bedaquiline and delamanid have been administered for the treatment of patients with multidrug-resistant/rifampicin-resistant tuberculosis after the official approval in South Korea. This study aimed to assess and compare the final treatment outcomes of patients who received bedaquiline with those of patients who received delamanid. Methods This is a nationwide cohort study of patients with multidrug-resistant/rifampicin-resistant tuberculosis in whom bedaquiline or delamanid was administered from 1 September 2016 to 28 February 2018, after receiving the official approval in South Korea. Patients were classified into the bedaquiline and delamanid group according to the first used drug. We evaluated and compared the final treatment outcomes between the groups. Results During the study period, 284 patients with multidrug-resistant/rifampicin-resistant tuberculosis were approved to use bedaquiline or delamanid and 260 were included in the final analysis; 119 (45.8%) and 141 patients (54.2%) were classified into bedaquiline and delamanid groups, respectively. Among them, 30 patients (11.5%) exhibited additional resistance to second-line injectable drugs, 94 patients (36.2%) had additional resistance to fluoroquinolones, and 37 patients (14.2%) had resistance to both drugs. The overall treatment success rate was 79.2%. Initiation of bedaquiline rather than delamanid was not associated with treatment success (adjusted odds ratio,.671; 95% confidence interval,.350–1.285). Frequencies of adverse events were not significantly different between the 2 groups. Conclusions Initial choice of bedaquiline or delamanid did not make any significant difference in the final treatment outcome or the frequencies of adverse events among patients with multidrug-resistant/rifampicin-resistant tuberculosis. [ABSTRACT FROM AUTHOR]

Diverse structural frameworks are found in natural compounds and are well known for their chemical and biological properties; such compounds include the imidazoles and oxazoles. Researchers worldwide are continually working on the development of methods for synthesizing new molecules bearing these basic moiety and evaluating their properties and applications. To expand the knowledge related to azoles, this review summarizes important examples of imidazole and oxazole derivatives from 1,2‐dicarbonyl compounds, such as lapachones and phenanthrene‐9,10‐diones, not only regarding their synthesis and biological applications but also their photophysical properties and uses. The data concerning the latter are particularly scarce in the literature, which leads to underestimation of the potential applications that can be envisaged for these compounds. [ABSTRACT FROM AUTHOR]

In this work, NH2-substituted oxazoles and NO2/NF2/NHNO2-substituted ethylenes/acetylenes were designed and used as dienes and dienophiles, respectively, in order to develop new bridge-ring insensitive high energy compounds through the Diels-Alder reaction between them. The reaction type, reaction feasibility and performance of reaction products were investigated in detail theoretically. The results showed that dienes most possibly react with dienophiles through the HOMO-diene controlled normal Diels-Alder reaction at relatively low energy barrier. Tetranitroethylene could react with the designed dienes much more easily than other dienophiles, and was employed to further design 29 new bridge-ring energetic compounds. Due to high heat of formation, density and oxygen balance, all designed bridge-ring energetic compounds have outstanding detonation performance, 16 of them have higher energy than HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and 2 others even possess comparative energy with the representative of high energy compounds CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12- hexaazaisowurtzitane). The predicted average h50 value of these bridge-ring energetic compounds is 83 cm, showing their low impact sensitivity. The NH2 groups could obviously impel the proceeding of Diels-Alder reactions, but would slightly decrease the energy and sensitivity performance. In all, the new designed bridge-ring compounds have both high energy and low sensitivity, and may be produced through Diels-Alder reactions at relatively low energy barrier. This paper may be helpful for the theoretical design and experiment synthesis of new advanced insensitive high energy compounds. [ABSTRACT FROM AUTHOR]

A gold‐catalyzed synthesis of polyfluoroalkylated oxazoles from N‐propargylamides under visible‐light irradiation has been developed. These reactions display excellent compatibility of radicals and gold catalysts under visible‐light irradiation. Mechanistic experiments indicate that polyfluoroalkyl iodides play a dual role in enhanced compatibility of radicals and gold catalysts through assisted protodeauration of vinyl gold and reactivated the gold catalyst. In addition, PPh3AuNTf2 not only activates N‐propargylamide to generate vinyl gold intermediate, but also greatly promotes homolysis of polyfluoroalkyl iodides under blue light irradiation. [ABSTRACT FROM AUTHOR]

The unexpected formation of an oxazole ring has occurred during synthesis of a copper(I) cyanide network polymer as part of our ongoing studies of the structural chemistry of these networks. Crystals of the title compound were formed during the synthesis of a previously reported CuCN network solid containing protonated N-methylethanolamine and have been characterized by single crystal X-ray structure analysis. The structure shows well-defined oxazole-2-iminium cations sitting in continuous channels along the short a-axis of the crystal in a new three-dimensional copper(I) cyanide polymeric network. Evidently, a reaction has occurred between the cyanide ion and the protonated N-methylethanolamine base.

Thiazole and oxazole are compounds with a heterocyclic nucleus that have attracted the attention of medicinal chemistry due to the great variety of biological activities that they enable. In recent years, their study has increased, finding a wide range of biological activities, including antifungal, antiparasitic, anti-inflammatory, and anticancer activities. This systematic review provides evidence from the literature on the antiproliferative and antitumor activities of thiazole and oxazole and their derivatives from 2014 to April 2020. Three bibliographical databases were consulted (PubMed, Web of Science, and Scopus), and a total of 32 studies were included in this paper based on our eligibility criteria. The analysis of the activity-structure relationship allows us to conclude that most of the promising compounds identified contained thiazole nuclei or derivatives.

The reactions of (2-chloroethynyl)diphenylphosphine oxide with diethyl 2-aminomalonate and of dimethyl (2-chloroethynyl)phosphonate with 2-amino-N1,N3-di(p-tolyl)malonamide or 2-aminomalonamide proceed chemo- and regioselectively to yield the corresponding 2-(phosphorylmethylene)oxazoles, namely diphenyl-[(4-ethoxycarbonyl-5-ethoxyoxazol-2-yl)methyl]phosphine oxide, dimethyl {[5-(p-tolylamino)-4-(p-tolylcarbamoyl)oxazol-2-yl]methyl}phosphonate, and dimethyl [(5-amino-4-carbamoyloxazol-2-yl)methyl]phosphonate, respectively. [ABSTRACT FROM AUTHOR]

• A set of naphthalene or oxazole-based compounds with positively charged groups was synthesized. • Their interaction with telomeric/oncogenic G-quadruplexes was studied by different biophysical techniques. • The oxazole-based derivatives proved to strongly and selectively recognize the target G-quadruplexes. • Molecular docking showed the preferential binding modes of the best ligands to the G-quadruplexes. • All oxazole-based ligands showed anticancer activity in the low micromolar range. New G-quadruplex-interactive and selective ligands are strongly required to evolve innovative, effective and minimally toxic anticancer agents. With this purpose, we have here synthesized and evaluated a mini-library of organic molecules featured by aromatic cores of different rigidity (naphthalene or bioxazole), decorated with pendant groups including positively charged moieties and/or H-bond donors/acceptors. By exploiting different biophysical techniques, we proved the ability of the bioxazole-based derivatives to strongly and selectively interact with telomeric and oncogenic G-quadruplexes, while the compound featured by a naphthalene core did not emerge as a good G-quadruplex ligand. Molecular docking studies demonstrated the ability of the bioxazole-based ligands to preferentially target the outer G-tetrads of both telomeric and oncogenic G-quadruplexes, by positioning their cores on the G-tetrads in a symmetrical or asymmetrical way respectively, with the pendant groups pointing towards or away from the grooves. All bioxazole-based ligands showed anticancer activity in the low micromolar range. Particularly, the bioxazole derivative bearing piperazine groups was the most active compound of the investigated series, whereas the derivatives bearing morpholine groups were the most selective ones on cancer cells, in full agreement with their ability to act as the strongest and most selective G-quadruplex ligands, respectively. [ABSTRACT FROM AUTHOR]

Abstract Pimprinols A, B, and C are bacterial 5-(3-indolyl)oxazole alkaloids that have been isolated from Streptomyces sp. Lv3–13. In this paper, we report a new synthesis of pimprinol A and the first total synthesis of pimprinol B and pimprinol C. In addition, antipodes of the naturally occurring pimprinols A and C, as well as the racemates of these two alkaloids were also prepared. In the pivotal step, the 1,3-oxazole ring was constructed by a Nicolaou’s modified Robinson–Gabriel cyclization.

The title compound, C21H16N2O2, consists of an imidazolidine unit linked to two phenyl rings and two prop-2-yn-1-yl moieties. The imidazolidine ring is oriented at dihedral angles of 79.10 (5) and 82.61 (5)° with respect to the phenyl rings, while the dihedral angle between the two phenyl rings is 62.06 (5)°. In the crystal, intermolecular C—HProp...OImdzln (Prop = prop-2-yn-1-yl and Imdzln = imidazolidine) hydrogen bonds link the molecules into infinite chains along the b-axis direction. Two weak C—HPhen...π interactions are also observed. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (43.3%), H...C/C...H (37.8%) and H...O/O...H (18.0%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that the C—HProp...OImdzln hydrogen-bond energy in the crystal is −40.7 kJ mol−1. Density functional theory (DFT) optimized structures at the B3LYP/6–311G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.

Abstract Base-induced cyclization of active methylene isocyanides with carbamimidothioates for the synthesis of N,1-aryl-4-tosyl/ethylcarboxy-1H-imidazol-5-amines is reported. The diversity of the reactions is exemplified by using various carbamimidothioates obtained from symmetrical N,N-disubstituted, unsymmetrical N,N,N-trisubstituted, and unsymmetrical N,N-disubstituted thioureas. This diversity is further enriched by different isocyanides. A mechanism for the formation of the title compounds is proposed.

The title compound, C20H16Cl2N2O3S, is built up from a dihydrobenzothiazine moiety linked by –CH– and –C2H4– units to 2,4-dichlorophenyl and 2-oxo-1,3-oxazolidine substituents, where the oxazole ring and the heterocyclic portion of the dihydrobenzothiazine unit adopt envelope and flattened-boat conformations, respectively. The 2-carbon link to the oxazole ring is nearly perpendicular to the mean plane of the dihydrobenzothiazine unit. In the crystal, the molecules form stacks extending along the normal to (104) with the aromatic rings from neighbouring stacks intercalating to form an overall layer structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (28.4%), H...Cl/Cl...H (19.3%), H...O/O...H (17.0%), H...C/C...H (14.5%) and C...C (8.2%) interactions. Weak hydrogen-bonding and van der Waals interactions are the dominant interactions in the crystal packing. Density functional theory (DFT) optimized structures at the B3LYP/ 6–311 G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO—LUMO behaviour was elucidated to determine the energy gap.

In the title compound, C17H14N4O3, the indazole unit is planar to within 0.0171 (10) Å and makes dihedral angles of 6.50 (6) and 6.79 (4)°, respectively, with the nitro and pendant phenyl groups. The conformation of the oxazole ring is best described as an envelope. In the crystal, oblique stacks along the a-axis direction are formed by π–π stacking interactions between the indazole unit and the pendant phenyl rings of adjacent molecules. The stacks are linked into pairs through C—H...O hydrogen bonds. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (36.3%), O...H/H...O (23.4%), C...H/H...C (13.4%) and N...H/H...N (11.4%) interactions.

Abstract Background In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities. Results and discussion The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively. Conclusion The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC50 = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC50 = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

The regioselective iodination of different 2‐mono‐, 3‐mono‐ and 2,3‐disubstituted 6‐aminoquinoxalines, which takes place at their 5‐position, was rationalized on the basis of Hückel theory calculations. Oxazolo‐ and thiazolo[5,4‐f]quinoxaline analogues of reported disease‐related protein kinases inhibitors were synthesized from the obtained 6‐amino‐5‐iodoquinoxalines by using as key step copper‐catalyzed azole ring formation. Pyrazino[b,e]isatins were obtained, for the first time, from the same substrates by recourse to Sonogashira coupling, alkyne hydration, and oxidative cyclization. The absorption and emission properties of the most promising compounds were recorded. In addition, most of the synthesized polycycles were evaluated as protein kinase inhibitors and for their antiproliferative activity towards cancer cells. [ABSTRACT FROM AUTHOR]

5-Hydroxymethylfurfural (5-HMF) is a renewable platform chemical used as a source for obtaining diverse fine chemicals. In this letter, we report the synthesis of 5-HMF-based oxazole compounds. While 5-HMF could be easily converted into the oxazole derivative through the Van Leusen reaction, the direct arylation step needed to access the final compounds was problematic at first. After optimization, a palladium-catalyzed procedure has been developed and used for the synthesis of a series of 33 derivatives. This article reports an extension of the late-stage CH arylation reaction as an application to the oxazole platform derived from biosourced 5-HMF. The challenges in the preparation of the derivatives containing some electron-withdrawing substituents were overcome by the use of a palladium-free method. [ABSTRACT FROM AUTHOR]

In the title compound, C33H26N4O4, the two fused five-membered rings and their N-bound aromatic substituents form a pincer-like motif. The relative conformations about the three chiral carbon atoms are established. In the crystal, a combination of C--H⋯O and C--H⋯N hydrogen bonds and C--H⋯π(ring) inter-actions leads to the formation of layers parallel to the bc plane. A Hirshfeld surface analysis indicates that the most significant contributions to the crystal packing are from H⋯H (44.3%), C⋯H/H⋯C (29.8%) and O⋯H/H⋯O (15.0%) contacts. [ABSTRACT FROM AUTHOR]

The development of the intramolecular Diels–Alder cycloaddition- of azole heterocycles, i.e. oxazoles (IMDAO), imidazoles (IMDAI), and thiazoles (IMDAT), has had a significant impact on the efficient preparation of heterocyclic intermediates and natural products. In particular, highly efficient and versatile IMDAO reactions have been utilized as a key step in several synthetic schemes to provide alkaloids and terpenoid target molecules. More limited studies have been performed on IMDAI and IMDAT cycloadditions. Some drawbacks, such as the occasionally- challenging preparation of IMDA precursors, are also highlighted in this review. Perspectives are provided on how IMDAI and IMDAT- transformations can be further expanded for target-directed syntheses. 1 Introduction 2 Oxazoles 2.1 IMDAO Approaches to Furanosesquiterpenes and Furanosteroids 2.1.1 Syntheses of Highly Oxygenated Sesquiterpenes 2.1.2 Syntheses of (±)-Gnididione and (±)-Isognididione 2.1.3 Synthesis of (±)-Stemoamide 2.1.4 Synthesis of (±)-Paniculide A 2.1.5 Syntheses of (+)- and (–)-Norsecurinine 2.1.6 Synthesis of Evodone 2.1.7 Syntheses of (±)-Ligularone and (±)-Petasalbine 2.1.8 Syntheses of Imerubrine, Isoimerubrine, and Grandirubrine 2.1.9 Syntheses of Furanosteroids 2.1.10 Syntheses of Substituted Indolines and Tetrahydroquinolines 2.2 IMDAO Approaches to Pyridines: the Kondrat'eva Reaction 2.2.1 Syntheses of Suaveoline and Norsuaveoline 2.2.2 Synthesis of Eupolauramine 2.2.3 Syntheses of (–)-Plectrodorine and (+)-Oxerine 2.2.4 Synthesis of Amphimedine 2.2.5 Synthetic Approach to the Western Segment of Haplophytine 2.2.6 Synthesis of Marinoquinoline A 2.2.6.1 IMDAO Approach to Marinoquinoline A 2.2.6.2 Scope of Allenyl IMDAO Cycloaddition 2.3 Lewis Acid Catalysis in IMDAO Reactions 2.3.1 Effects of Europium Catalysts on IMDAO Reactions 2.3.2 Effects of Copper Catalysts on IMDAO Reactions 3 Imidazoles 4 Thiazoles 4.1 Syntheses of Menthane and Eremophilane 4.2 Further Comments on the Intramolecular Cycloadditions of Thiocarbonyl Ylides 5 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

Methods for the synthesis of 3-methyl-N-(1,5-dinitro-8-oxo-3-azabicyclo[3.3.1]non-6-en-7-yl)benzamide and 10-methyl-4-phenyl-1,8-dinitro-3-oxa-5,10-diazatricyclo[6.3.1.02.6]dodeca-2(6),4-diene from N-(2-hydroxy-3,5-dinitrophenyl)benzamide by Mannich condensation of the corresponding σ-adducts was developed. It is shown that the obtained substances can interconvert to each other under certain conditions.

Described in this paper are studies on the preparation of three classes of dimethylpyridinols derived from pyridoxine fused with aminooxazole, aminoimidazole, and aminopyrrole. The key feature of this synthetic strategy is the manipulation of hydroxymethyl moiety of C(5)-position of the pyridoxine starting material along with the installation of an amino group at C(6)-position. Efficient and practical synthesis for the oxazole- and imidazole-fused targets was accomplished, while the instability of the pyrrole-fused one was observed.

Sulphonamide derived oxazoline hybrid compounds showed neuroprotective effects by inducing autophagy. In the present study, a series of sulphonamide containing oxazoline hybrids were synthesized and their neuroprotective efficacy in neuronal cell lines was explored. All the compounds showed moderate to good neuroprotection against adrenal medulla cell lines (PC 12). Compound 6 j had good neuroprotective activity against PC 12 cell lines showing increased expression of autophagy regulatory proteins (ATG7, LC 3B, p62, Beclin‐1) and anti‐apoptotic proteins (Bcl‐2) and also decreased expression of pro‐apoptotic proteins (Bax and Bad). This study demonstrated clearly that compound 6 j showed neuroprotective effect through the induction of autophagy and opens up new avenues for a new class of compounds as neuroprotective therapeutic agents. [ABSTRACT FROM AUTHOR]

Over the last few decades, iodine has been a stellar catalyst for numerous organic transformations such as C−H activation, hetero‐annulation and coupling reactions. In heterocyclic chemistry, iodine is primarily an economical and eco‐friendly catalyst that fascinates the construction of C−O/C−N bonds via oxidative, radical, and electrophilic pathways. Several novel Iodine‐catalyzed methodologies have been reported, presenting advances in heterocyclic synthesis with regioselectivity, wide substrate scope and excellent yields. Furthermore, feasible protocols implemented to get oxazole annulation in literature have an enormous impact on new synthetic applications. Therefore, this literature analysis comprises advancements in the field of iodine‐mediated 1,3‐oxazole synthesis since 1998. For the ease of the readers, the reported methodologies have been categorised based on iodine functioning in reactions with insight into the reaction mechanisms and highlights. [ABSTRACT FROM AUTHOR]

This review is devoted to the recent advances in the chemistry of methylene isocyanides with C=C, C≡C, C=O, and C=N bonds. In this paper, we show a variety of [3+2] cycloaddition reactions for isocyanides, carried out both under catalytic and non‐catalytic conditions. In addition, we also focused on diastereo‐ and enantioselectivity data. [ABSTRACT FROM AUTHOR]

Twelve compounds containing a sulphur- or oxygen-based heterocyclic core, 1,3- oxazole or 1,3-thiazole ring with hydroxy, methoxy and methyl terminal substituent, were synthesized and characterized. The molecular structures of these compounds were performed by elemental analysis and different spectroscopic tequniques. The liquid crystalline behaviors were studied by using hot-stage optical polarizing microscopy and differential scanning calorimetry. All compounds of 1,4- disubstituted benzene core with oxazole ring display liquid crystalline smectic A (SmA) mesophase. The compounds of 1,3- and 1,4-disubstituted benzene core with thiazole ring exhibit exclusively enantiotropic nematic liquid crystal phases. [ABSTRACT FROM AUTHOR]

An electrochemical iodine‐mediated transformation of enamino‐esters for the synthesis of 2H‐azirine‐2‐carboxylates is presented. In addition, a thermic conversion of azirines to 4‐carboxy‐oxazoles in quantitative yield without purification was described. Both classes 2H‐azirines‐2‐carboxylates and the 4‐carboxy‐oxazoles are substructures in natural products and therefore are of considerable interest for synthetic and pharmaceutical chemists. The optimization was not performed in a conventional manner with a one‐factor‐at‐a‐time process but with a Design of Experiments (DoE) approach. Beside a broad substrate scope the reaction was also employed to a robustness screen, a sensitivity assessment, and complemented with mechanistic considerations from cyclic voltammetry experiments. [ABSTRACT FROM AUTHOR]

Treatment of O‐(β‐arylethyl) arylimidates with 1,3‐diiodo‐5,5‐dimethylhydantoin (DIH) under irradiation with a tungsten lamp in 1,2‐dichloroethane gave the corresponding 2,4‐diaryl‐5‐iodoxazoles and 2,4‐diaryloxazoles in good to moderate yields, respectively, depending on the aryl group. It was proposed that the reactions proceeded through the formation of N‐iodoimidates by the reaction of O‐(β‐arylethyl) arylimidates with DIH, followed by the formation of iminyl radicals via homolytic N–I bond cleavage, the 1,5‐H shift by the iminyl radicals, the C–I bond formation of the formed carbon‐centered radicals with iodine, the nucleophilic cyclization by the imino groups to form 2,4‐diaryloxazolines, the oxidation of the formed 2,4‐diaryloxazolines to 2,4‐diaryloxazoles, and the iodination of the formed 2,4‐diaryloxazoles to 2,4‐diaryl‐5‐iodoxazoles with DIH. [ABSTRACT FROM AUTHOR]

A series of amide derivatives of azaindole-oxazoles (11a–n) were designed and synthesized and their structures were confirmed by 1HNMR, 13CNMR and mass spectral analysis. Further, these derivatives were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC50 values 0.034 and 0.036 µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC50 values. [ABSTRACT FROM AUTHOR]

The parent compound (6-methyl-2,6 dihydro[1,2,4-triazino[4,3-b]indazol-3(4H)-one was prepared from reaction of ((1-Methyl-1H-indazol-3-yl)-hydrazine) with ethyl bromoacetate, then (41) new compounds were synthesized. The first compound (1) was synthesized from condensation of parent compound with 2-chloro benzaldehyde in basic medium, after that novel compounds was derived from chalcone (1). Five, six and seven member ring were produced from cyclized of α,β unsaturated system with several materials such as (malononitrile, ethyle cyanoacetate, 2-amino phenol, 2-amino thiophenol, phenylene diamine mercapto acetic acid, phenyl hydrazine, ect) to offered (1-15) derivatives. The pyridazine and pyridazinone compounds (17-20) were synthesized from treatment of parent compound with dimethyl amine, methyl amine, chloro acetyl chloride and formic acid, respectively while derivative (21) produced from reaction of (20) with urea by. Besides that, compound (19) was a good key to synthesize oxazol, thiazol, thiazine and hydrazino derivatives (22, 23, 24 and 25) respectively. Hydrazino derivative (25) was also used for synthesis (26-28) derivatives. In additional to that, derivative (2) was a worthy core and a key intermediate for the synthesis of several new fused heterocycles in this work. Acylation of amino group in (2) with acetic anhydride was gave (29), while (2) cyclized with chloroacetic acid or malononitrile aes affered (30, 31) respectively. On the other side, amino group of (2) underwent to reaction with phenylisothiocyanate, ethylacetoacetate, urea, thiourea, phenylisothiocyanate and formamide to produce (32, 33, 34, 35, 37 and 38). While when derivative (2) cyclized with ethyl chloroacetate led to formation (36). Compound (2) was cyclized under heating with formamide, formic acid to give pyrimidine and pyrimidinone derivatives (39, 40) respectively. Finally, in presence of ethanol and hydrochloric acid, derivative (33) underwent to ring closure to produce (41). The structures, of all synthesized compounds were confirmed by using spectroscopic analysis such as UV, FTIR, 1H-NMR and 13CNMR spectral. [ABSTRACT FROM AUTHOR]

We herein report a modified approach for the synthesis of some pharmacologically relevant oxazole derivatives linked with amides under mild conditions. The utilization of polymer-supported triphenylphosphine (poly-TPP) as a phosphine ligand for generating the key iminophosphorane intermediate was found to be vital for achieving the synthesis of oxazole in room temperature. This alternative approach relying on the cyclization reaction of readily available phenacyl azide and phenyl isothiocyanate rendered the oxazole derivative 3a in excellent yield. This methodology has been applied for the synthesis of a more decorated oxazole derivative 3b having ester functionality and was further converted to different amides under microwave irradiation in good to excellent yields in the later stage. [ABSTRACT FROM AUTHOR]

Excited state intramolecular proton transfer (ESIPT) processes typically occur when photoexcited molecules relax via a tautomeric proton transfer event in the excited state, and it is known to depend on the properties of donor and acceptor groups. In this work, we employed ground state and Time Dependent Density Functional Theory aiming at studying the ESIPT viability on triphenyl-substituted heterocyclic (imidazole, oxazole, and thiazole) tert-butyl derivatives. For all compounds, the formation of a keto tautomer is favored once an excited state is generated from a ground state enol tautomer. The expected tert-butyl electron donor effect and enol form stabilization is verified in the ground state, but the opposite is observed for the excited state. We found that tert-butyl substituted compounds have reduced HOMO-LUMO gap, exhibit barrierless proton transfer in the excited state and stronger Hydrogen bond after light excitation. [ABSTRACT FROM AUTHOR]

A new convenient procedure for the synthesis of oxazolines from tosylmethyl isocyanide (TosMIC) and aldehydes using imidazole as an efficient catalyst has been reported. The synthesized oxazolines were able to be protected from the oxidation by using just water both as a good solvent and anti oxidant. All the synthesized compounds show good anti biofilm activity against Staphylococcus epidermidis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Utilizing in silico fragment-based drug design, we identified potent compounds targeting EGFR in cancer cells, inducing apoptosis and cell cycle arrest. The ongoing research in cancer treatment underscores the significance of dual epidermal growth factor receptor (EGFR) kinase inhibitors targeting both mutant and wild-type variants. In this study, employing in silico fragment-based drug design (FBDD) and computational analysis, we have successfully developed a novel chemical series of 2-(pyrimidin-4-yl)oxazole-4-carboxamide (16a-j) derivatives designed as dual EGFR kinase inhibitors. A comparative in vitro anticancer profile of the newly synthesized compounds (16a-j) was tested against a panel of five human cancer cell lines like prostate cancer (PC3 & DU-145), lung cancer (A549), human liver cancer (HEPG2), and breast cancer (MDA-MB-468) by employing MTT method. In this experiment a well-known anticancer agent, Etoposide was used as positive control. Most of the derivatives demonstrated significant cytotoxicity, ranging from excellent to moderate levels. The IC 50 values for the synthesized compounds observed between 0.10 ± 0.052 to 9.83 ± 5.96 µM, while the positive control exhibited a range of 1.97 ± 0.45 µM to 3.08 ± 0.135 µM. These results indicate that the synthesized compounds demonstrate higher cytotoxic potency in comparison to the reference compound. Furthermore, all these compounds underwent screening against normal Vero cell lines to assess their cytotoxicity. In each case, the observed cytotoxicity values (IC 50) were higher than 22 µM, affirming the compounds selectivity for cancer cell lines. Among the compounds investigated, three compounds (16a , 16e , and 16i) exhibited notable cytotoxicity, while two compounds (16 g and 16 h) demonstrated exceptional cytotoxicity. The selectivity index of the tested compounds indicates a pronounced preference for targeting cancer cell lines over normal cells. Furthermore, all the compounds 16a-j underwent assessment for their EGFR kinase inhibitory activity against both EGFRWT and mutated EGFRT790M. The results unveiled the potential eligibility of this new series of compounds as effective EGFR inhibitors. Moreover, compound 16 h underwent additional testing for cell cycle analysis, revealing its capability to arrest the cell cycle in the G2/M phase and induce apoptosis at the IC 50 concentration. [ABSTRACT FROM AUTHOR]

Coumarins are natural heterocycles that widely contribute to the design of various biologically active compounds. Fusing different aromatic heterocycles with coumarin at its 3,4-position is one of the interesting approaches to generating novel molecules with various biological activities. During our continuing interest in assembling information about fused five-membered aromatic heterocycles, and after having presented mono-hetero-atomic five-membered aromatic heterocycles in Part I. The current review Part II is intended to present an overview of the different synthetic routes to coumarin (benzopyrone)-fused five-membered aromatic heterocycles with multi-heteroatoms built on the pyrone ring, covering the literature from 1945 to 2021.

Eight novel pyridyl–oxazole carboxamides were evaluated against fungi and displayed good fungicidal activities against Botrytis cinereal and Rhizoctonia solani. Preliminary bioassay results indicated that at 100 mg/L, compounds 6a–6e, 6g and 6h exhibited 100% fungicidal activities against Botrytis cinerea, and the compound 6b to Rhizoctonia solani at 100%. Then, the zebrafish embryo acute toxicity test was performed to assess the toxicity of 6b and 6c. A series of malformations appeared, when the zebrafish embryos were exposed to 6b and 6c, such as delayed yolk sac resorption, significant shortening of body length, pericardial edema, bending spine, lack of melanin, heart hemorrhage, head hemorrhage, delayed swim sac development, yolk malformation and head malformation. In addition, the acute toxicity of 6b to zebrafish embryo is 4.878 mg/L, and 6c is 6.257 mg/L.