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Antimicrobial activities of some newly synthesized substituted benzosuberone and its related derivatives

A series of substituted benzosuberone scaffold fused with pyrazole, isoxazole, pyrimidine and triazole moieties were synthesized and evaluated as antimicrobial agents. Some reactions were performed under microwave irradiation, resulted in short time reactions and surprisingly high yields. Some of the obtained products showed remarkable antimicrobial activities and the most active products 7b, 9, 13 and 14 were further tested to evaluate their Minimum Inhibitory Concentration (MIC) value at 125 mug/mL. The structures of new compounds were proved by their elemental analyses and spectral data.

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Isoxazole – Wikipedia,
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Trisubstituted heterocyclic compounds and their use as fungicides

Compounds of general formula (I):in which:, Hetrepresents a five or six membered saturated, partially unsaturated or aromatic ring containing between one and six heteroatoms of the group N, O, S, in which the heterocycle is substituted in an adjacent manner with -P-Q1-T-Q2, -GZ and Y, such that the substituant -GZ is adjacent to both., the other substituants being as defined in the description,process for preparing these compounds,fungicidal compositions comprising these compounds,processes for treating plants by applying these compounds or compositions.

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A retrospective look at anthranilic diamide insecticides: discovery and lead optimization to chlorantraniliprole and cyantraniliprole

Anthranilic diamides are an important commercial synthetic class of insecticides (IRAC Group 28) that bind to the ryanodine receptor with selective potency against insect versus mammalian forms of the receptor. The first commercialized diamide, chlorantraniliprole, has exceptional activity against lepidopteran pests. The second anthranilamide product, cyantraniliprole, has excellent cross-spectrum activity against a range of insect orders, including both lepidopteran and hemipteran pests. Here, a retrospective look is presented on the discovery of the class, along with chemistry highlights of the lead evolution to both products.

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Structural aspects of high affinity ligands for the alpha4beta2 neuronal nicotinic receptor

Neuronal nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of related ion channels that are widely distributed throughout the central and peripheral nervous systems. They all share a common architecture of five subunit proteins that combine at the cell surface to create a ligand-gated cation permeable pore. Significant effort is currently being expended by medicinal chemistry teams to synthesize ligands that exhibit selectivity for central over peripheral nAChR subtypes. Within the CNS, multiple nAChR subtypes are recognized, and the discovery of ligands exhibiting selectivity among these subtypes offers an opportunity for the development of novel therapeutic agents. The alpha4beta2 subtype is one of the most abundant nAChR subtypes within the CNS, and has been the primary focus of high affinity ligand design. Nicotine (1), and more recently, epibatidine (2) have served as structural templates for the design of the majority of active compounds. Although the diversity of nAChR ligands is growing, the structural requirements necessary for high affinity binding with the alpha4beta2 receptor remain poorly understood. The putative pharmacophoric elements common to all potent alpha4beta2 ligands include (1) a basic or quaternized nitrogen atom, and (2) a less basic nitrogen or a carbonyl oxygen that presumably interact with electron rich and electron deficient sites on the receptor, respectively. The family of currently known high affinity analogs consists of a diverse array of azacycles containing a basic amine. Several additional basic amine fragments have been identified, including the pyrrolizidine nucleus (exemplified by 8) and the 2-azabicyclo[2.2.1]heptane skeleton (exemplified by 9). In addition, we have found that the furo[2,3-b]pyridine heterocycle (compound 10) serves as useful bioisosteric replacement for the pyridyl substituent of nicotine. A preliminary pharmacophore model is proposed in which a reasonable superposition of the putative pharmacophoric elements of the diverse array of high affinity ligands for the alpha4beta2 nAChR reported herein may be accommodated.

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Recent advances in computing heteroatom-rich five- and six-membered ring systems

Recent developments in computer technology and the increasing efficiency and accuracy of current ab initio and density functional programs allow the investigation of increasingly complex systems. Molecules that could be treated only at the semiempirical level ten years ago can now be computed at the density functional or the MP2 level with basis sets of double-zeta quality. Very often, these calculations are accurate enough to explain experimental findings, and consequently many experimental studies are augmented by quantum chemical calculations. However, in many cases just a few kilocalories per mole may decide between different reaction mechanisms, different explanations of physical effects, or even a preferred tautomer or conformer. Since the inherent errors of MP2 and DFT calculations are still significantly larger than chemical accuracy, high-level calculations are mandatory for many problems. This holds particularly true for the investigation of reaction barriers involving bond-breaking processes. Although these problems have been recognized by many investigators, a substantial number of papers lack sufficient accuracy. This accuracy problem appears to be more severe for heteroatom-rich species than for other systems, in particular for systems with adjacent heteroatoms. However, DFT calculations were found to cope surprisingly well with the geometric parameters of most of these systems. As is common in heterocyclic chemistry, many studies concern tautomeric equilibria. While quantum chemical calculations are straightforward for the question of the most stable isomer, experiments are sometimes very demanding. Therefore, quantum chemistry can easily provide answers that may require substantial experimental effort. Comparatively few studies concern the investigation of entire reaction paths. This is much more demanding than computing a limited number of tautomers, of course, but usually provides a very detailed picture of the reaction mechanism. In certain cases, it was only possible to judge the nature of a chemical reaction on the basis of quantum chemical calculations. Most studies concerning pyrimidines originate from biochemical questions. Since these systems are dominated by hydrogen-bonding and/or dispersion contributions, methods beyond the Hartree-Fock level are mandatory. The success of quantum chemical studies in this field is impressive and many effects could be explained on the basis of these theoretical investigations.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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A facile one-pot synthesis of 7-substituted pyrazolo[1,5-a]pyrimidines by base induced three-component reaction

The preparation of steroid/nonsteroid fused 7-substituted pyrazolo[1,5-a]pyrimidines is described by a one-pot reaction of steroidal/nonsteroidal ketones, aromatic aldehydes and 3-amino-1H-pyrazoles/5-amino-1H-pyrazoles in the presence of potassium tert-butoxide in good yield under reflux condition in ethanol.

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Estimation of pure component properties: Part 1. Estimation of the normal boiling point of non-electrolyte organic compounds via group contributions and group interactions

An improved group contribution method for the estimation of the normal boiling point of non-electrolyte organic compounds was developed using experimental data for approximately 2850 components stored in the Dortmund Data Bank (DDB). The new model is based on a method published earlier, which was extended using a steric parameter, additional corrections and group interaction parameters as well as several additional groups for extended range of applicability. The mathematical formalism was modified to allow for separate examination and regression of individual contributions. The results of this separate examination lead to the detection of unreliable data and the definition of further structural groups. For the boiling point prediction, only the molecular structure of the compound is used. The results of the new method are compared to the previous work and several currently used methods and are shown to be far more accurate and reliable. The detailed comparison for a large number of different sets of chemically similar compounds allows one to access the probable estimation error of the different methods. Structural groups were defined in a standardized form and fragmentation of the molecular structures was performed by an automatic procedure to eliminate any arbitrary assumptions.

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Flash vacuum pyrolysis of 2-alkoxyiminated alkyl alpha-pyrone and 1,3-diazine derivatives

Flash vacuum pyrolysis of 6-ethyl-3-(1-ethoxyiminopropyl)-4-hydroxy-2H-pyrane-2-one (1) and 1,3-dimethyl-5-(1-ethoxyiminopropyl)-6-hydroxy-1,2,3,4-tetrahydropyrimidine-2,4- dione (2) were studied between 300 and 400C, with nitrogen as the carrier gas. Compound 1 afforded a 1-azirine and the isomeric oxazole, while an oxime and an amide were the reaction products of 2. The difference in reactivity is discussed in terms of the tautomeric structures present in both compounds.

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Reactions of 5-formyl-and 5-acyl-3,4-dihydro-2H-pyrans and their annelated analogs with nucleophiles

beta-Carbonyl-substituted dihydropyrans are highly useful heterocyclic compounds showing important application in organic synthesis. The increased susceptibility of the dihydropyran ring to the action of various nucleophiles makes these compounds valuable building blocks for the synthesis of a wide variety of hetero- and carbocyclic compounds. On the other hand, the presence of two non-equivalent electrophilic centers poses the problem of selectivity of reactions involving nucleophiles. This chapter will survey the reactivity of 5-formyl- and 5-acyl-3,4-dihydro-2H-pyrans and their annelated analogues with C-, N- and some other mono- and binucleophiles.

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Design and synthesis of NO-releasing betulinic acid derivatives as potential anticancer agents

A total of 16 targeted NO-releasing betulinic acid (BA) derivatives were designed and synthesized as potential anticancer agents. Most IC50 values were under 1.0 muM in vitro test against HepG2 and B16. The result suggested that derivatives of BA with alpha,beta-unsaturated ketone skeleton possessed significant cytotoxic activities than the others, among which derivatives with three carbons in diol linker (15b and 15c) exhibited the highest anti-cancer activity. NO-releasing amount detection of partial target compounds suggested that NO-releasing amount of this series of BA derivatives positively correlates with their cytotoxic activities. The anti-angiogenic activity of partial target compounds on zebrafish embryos in our experiment did not show any effects on the SIVs, however, they exhibited different influence on ISVs, with only 15a and 15d better than the negative control.

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Isoxazole – Wikipedia,
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