Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors.

Recently, nanomedicine had the potential to increase the delivery of active compounds to specific cell sites. Nano-LDL particles are recognized as an excellent active nano-platform for cancer-targeted delivery. Loading of therapeutic agents into nano-LDL particles achieved by surface loading, core loading, and apolipoprotein-B100 interaction.

Green Protocol for the Novel Synthesis of Thiochromeno[4,3-]pyridine and Chromeno[4,3-]pyridine Derivatives Utilizing a High-Pressure System.

A suitable and effective Q-tube-assisted strategy for the synthesis of novel, unrivalled thiochromeno[4,3-]pyridine and chromeno[4,3-]pyridine derivatives has been sophisticated, which includes ammonium acetate-mediated cyclocondensation reactions between 3-oxo-2-arylhydrazonopropanals and heterobenzocyclic ketones such as thiochroman-4-one and chroman-4-one, respectively. The high-pressure Q-tube reactor was shown to be superior to conventional heating. Furthermore, this Q-tube reactor-assisted protocol is safe owing to facile pressing and sealing, a broad substrate scope, and simple work-up and purification processes, as well as being scalable and having a high atom economy.

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-]indole Derivatives.

An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido[1,2-][1,2,4]triazine and pyrido[1',2':2,3][1,2,4]triazino[5,6-]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under high-pressure conditions.

High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents.

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis.

Palladium-Catalyzed Q-Tube-Assisted Protocol for Synthesizing Diaza-dibenzo[,]azulene and Diaza-benzo[]fluorene Derivatives via O Acid-Promoted Cross-Dehydrogenative Coupling.

An appropriate and efficient Q-tube-assisted palladium-catalyzed strategy for the synthesis of novel, unparalleled diaza-dibenzo[,]azulene and diaza-benzo[]fluorene derivatives has been sophisticated, which includes oxygen and AcOH-induced oxidative C(sp)-C(sp) cross-dehydrogenative coupling reactions of 1-amino-2-imino-4-arylpyridine-3-carbonitriles with benzocyclic ketones such as benzosuberone, tetralone, thiochromone, and chromone, respectively. This Q-tube gas purging kit assisted-protocol features safe due to easy pressing and sealing, a wide substrate scope, easy workup and purifying phases, and the use of O as a benign oxidant, in addition to being scalable and having a high atom economy. The suggested mechanistic pathway includes a formal dehydrative step followed by palladium AcOH-induced C(sp)-C(sp) oxidative cross-coupling.

Author Correction: The first Q-Tube based high-pressure synthesis of anti-cancer active thiazolo[4,5-c]pyridazines via the [4 + 2] cyclocondensation of 3-oxo-2-arylhydrazonopropanals with 4-thiazolidinones.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A facile, practical and metal-free microwave-assisted protocol for mono- and bis-[1,2,4]triazolo[1,5-]pyridines synthesis utilizing 1-amino-2-imino-pyridine derivatives as versatile precursors.

A facile and effective assembly of several substituted functionalized mono- and bis-[1,2,4]triazolo[1,5-]pyridines from conveniently attainable 1-amino-2-imino-pyridines has been established. Using microwave irradiation speeds up the reaction efficiently, proceeding with a higher rate and yields than with conventional heating. In the presented protocol, a broad variety of carboxylic acids could be employed effectively to synthesize the respective derivatives direct metal-free C-N bond construction.

The first Q-Tube based high-pressure synthesis of anti-cancer active thiazolo[4,5-c]pyridazines via the [4 + 2] cyclocondensation of 3-oxo-2-arylhydrazonopropanals with 4-thiazolidinones.

A novel and efficient protocol for the synthesis of thiazolo[4,5-c]pyridazine derivatives was developed. The approach utilizes a high pressure Q-Tube reactor to promote cyclocondensation reactions between 3-oxo-2-arylhydrazonopropanals and 4-thiazolidinones. The process has a significantly high atom economy and a broad substrate scope, as well as being applicable to gram scale syntheses.

Synthetic Strategy for Pyrazolo[1,5-]pyridine and Pyrido[1,2-]indazole Derivatives through AcOH and O-Promoted Cross-dehydrogenative Coupling Reactions between 1,3-Dicarbonyl Compounds and -Amino-2-iminopyridines.

An efficient method has been developed for the synthesis of uniquely substituted pyrazolo[1,5-]pyridine and pyrido[1,2-]indazole derivatives, which involves acetic acid and molecular oxygen promoted cross-dehydrogenative coupling reactions of respective β-ketoesters and β-diketones (like ethyl acetoacetate, ethyl benzoylacetate, methyl propionylacetate, acetylacetone, dimedone, 1,3-cyclohexanedione, and 1,3-cyclopentanedione) with -amino-2-iminopyridines. The proposed tentative mechanism involves formal acetic acid-promoted oxidative C(sp)-C(sp) dehydrogenative coupling followed by dehydrative cyclization under a catalyst-free condition within high atom economy processes.

Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(sp)-C(sp) Coupling Reactions between 1-Amino-2-imino-pyridines and 1-Aryl-5-pyrazolones.

A novel, metal catalyst-free, and efficient method has been developed for the synthesis of (pyrazol-4-ylidene)pyridine derivatives. The process involves dehydrogenative coupling of 1-amino-2-imino-pyridines with 1-aryl-5-pyrazolone derivatives utilizing O as the sole oxidant. The new method benefits from a high atom economy, efficiency, and substrate scope, as well as the simplicity of reaction and product purification procedures.

Scalable Sonochemical Synthetic Strategy for Pyrazolo[1,5-]pyridine Derivatives: First Catalyst-Free Concerted [3 + 2] Cycloaddition of Alkyne and Alkene Derivatives to 2-Imino-1-pyridin-1-amines.

A highly efficient and convenient one-pot sonochemical synthetic strategy has been sophisticated for synthesizing a novel class of polysubstituted pyrazolo[1,5-]pyridines via [3 + 2] cycloaddition of dialkyl acetylenedicarboxylates, ethyl propiolate, and alkenes to 2-imino-1-pyridin-1-amines under catalyst-free conditions. A series of uniquely substituted pyrazolo[1,5-]pyridines has been synthesized with a very good to excellent yield, and the mechanistic pathway that involves a [3 + 2] annulation process was also proposed. In this study, several spectroscopic tools of analyses were employed for structure elucidation, and the X-ray single-crystal technique was utilized to confirm the proposed mechanism and the regioselectivity.

l-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moiety sustainable sonochemical approach.

The efficient, highly convenient synthesis of polysubstituted pyridine derivatives was established the reaction of -(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidene malononitriles and arylidene ethyl cyanoacetates in the presence of l-proline as an efficient organocatalyst for this type of ultrasonic-mediated Michael addition. The mechanistic pathway and factors affecting this reaction were also established. The main characteristics of this procedure are high yields, use of a cost-effective catalyst, and easy work-up and purification.

Biological evaluation of benzosuberones.

Introduction: Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities.

Synthesis of a new class of Pyridazin-3-one and 2-amino-5-arylazopyridine derivatives and their utility in the synthesis of fused azines.

A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives 3 were formed as the sole isolable products in excellent yield. The 6-acetyl-3-oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding enaminone derivative 4, which reacts with a variety of aminoazoles to afford the corresponding azolo[1,5-a]pyrimidine derivatives 5-7.

Approaches towards the synthesis of a novel class of 2-amino-5-arylazonicotinate, pyridazinone and pyrido[2,3-d]pyrimidine derivatives as potent antimicrobial agents.

Background: Despite significant progresses in antimicrobial therapy, infectious diseases caused by bacteria and fungi remain a major worldwide health problem because of the rapid development of resistance to existing antimicrobial drugs. Therefore, there is a constant need for new antimicrobial agents. There are a large number of heterocyclic derivatives containing nitrogen atoms that possess a broad spectrum of biological activities including pyridine and pyridazine, which are two of the most important heterocycles in medicinal chemistry.

Organocatalysis in heterocyclic synthesis: DABCO as a mild and efficient catalytic system for the synthesis of a novel class of quinazoline, thiazolo [3,2-a]quinazoline and thiazolo[2,3-b] quinazoline derivatives.

Background: There are only limited publications devoted to the synthesis of especially thiazolo[3,2-a]quinazoline which involved reaction of 2-mercaptopropargyl quinazolin-4-one with various aryl iodides catalyzed by Pd-Cu or by condensation of 2-mercapto-4-oxoquinazoline with chloroacetic acid, inspite of this procedure was also reported in the literature to afford the thiazolo [2,3-b] quinazoline. So the multistep synthesis of the thiazolo[3,2-a]- quinazoline suffered from some flaws and in this study we have synthesized a novel class of thiazoloquinazolines by a simple and convenient method involving catalysis by 1,4-diazabicyclo[2.2.

4-Thiazolidinones in heterocyclic synthesis: synthesis of novel enaminones, azolopyrimidines and 2-arylimino-5-arylidene-4-thiazolidinones.

The 4-thiazolidinones 3a-d were used as a key intermediates for the synthesis of 2-arylimino-5-arylidene-4-thiazolidinones derivatives 7a–p via nucleophilic addition reactions with the arylidene malononitrile. Moreover the 4-thiazolidinones 3a and 3c condensed with the DMF-DMA to form the corresponding enamines 8 and 9 depending on the reaction conditions. Otherwise the 4-thiazolidinone 3b reacts regioselectively with DMF-DMA to afford the enaminones 10 and 11, respectively.

Acylation of heteroaromatic amines: facile and efficient synthesis of a new class of 1,2,3-triazolo[4,5-b]pyridine and pyrazolo[4,3-b]pyridine derivatives.

1,2,3-Triazolo[4,5-b]pyridines and pyrazolo[4,3-b]pyridines can be readily prepared via cyanoacetylation reactions of 5-amino-1,2,3-triazoles 1a,b and 4-amino- pyrazole 2 followed by subsequent cyclization of the formed cyanoacetamides. Reactions of amines 1a,b with a mixture of p-nitrophenylacetic acid and acetic anhydride under microwave irradiation conditions afforded the corresponding amides 15a,b that underwent cyclization to form 1,2,3-triazolo[4,5-b]pyridines 16a,b upon heating in DMF solutions containing sodium acetate. Reactions of 1a,b with active methylene compounds, including 17a-c, in the presence of zeolites as catalyst also afforded 1,2,3-triazolo[4,5-b]pyridine derivatives 20a-f via the intermediacy of triazole derivatives 19 and not 18.

Applications of 2-arylhydrazononitriles in synthesis: preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities.

In this effort, 2-arylhdrazononitriles were used as key synthons for the preparation of wide variety of new, uniquely substituted heterocyclic substances. In addition, the results of biological evaluations demonstrate that members of the group prepared have promising antimicrobial activities against Gram negative bacteria, Gram positive bacteria and Yeast. In the synthetic sequences, 3-(1-methyl-1H-indol-3-yl)-3-oxo-2-(phenylhydrazono)propanenitrile 2a and its 2-methyl derivative 2b were found to react with hydroxylamine hydrochloride to yield the corresponding indolyl-5-amino-2-phenyl-1,2,3-triazoles 4a,b.