Triethylammonium Hydrogen Sulfate [Et3NH][HSO4]-Catalyzed Rapid and Efficient Multicomponent Synthesis of Pyrido[2,3-d]pyrimidine and Pyrazolo[3,4-b]pyridine Hybrids.

An operationally simple, one-pot multicomponent reaction has been developed for the assembly of pyrido[2,3-d]pyrimidine and pyrazolo[3,4-b]pyridine derivatives (4a-4am) in excellent yields (92-94%) with high purity. The reactions were easy to perform simply by mixing of electron-rich amino heterocycles (including aminouracils and aminopyrazoles), aldehyde, and acyl acetonitrile in the presence of [Et3NH][HSO4] under solvent-free conditions. The remarkable feature of the present approach is that the ionic liquid possesses dual solvent-catalytic engineering capability. Results of this study revealed that 1 mmol of the ionic liquid catalyst under solvent-free conditions at 60 °C is the best reaction parameter for the construction of fused pyridine and pyrimidine derivatives in excellent yields. The present methodology showed good results under gram-scale conditions, thereby indicating its applicability in industrial as well as academic settings in the near future.

Rapid Construction of Substituted Dihydrothiophene Ureidoformamides at Room Temperature Using Diisopropyl Ethyl Ammonium Acetate: A Green Perspective.

An economic, sustainable, and straightforward environmentally friendly synthesis of highly diversified polyfunctional dihydrothiophenes is successfully achieved via diisopropyl ethyl ammonium acetate as a room-temperature ionic liquid. Multicomponent synthesis contains domino processes; the benefit of this present protocol is highlighted by its readily available starting materials, superior functional group tolerance, purity of synthesized compounds was checked by high-performance liquid chromatography results in up to 99.7% purity for the synthesized compounds, reaction mass efficiency, effective mass yield, and excellent atom economy. In addition, a series of 2-(N-carbamoyl acetamide)-substituted 2,3-dihydrothiophene analogs were synthesized, and selected samples were chosen for testing their in vitro antibacterial and antifungal activities. Furthermore, a molecular docking study against sterol 14α-demethylase could provide valuable insight into the mechanism of antifungal action providing an opportunity for structure-based lead optimization.

Efficient Rapid Access to Biginelli for the Multicomponent Synthesis of 1,2,3,4-Tetrahydropyrimidines in Room-Temperature Diisopropyl Ethyl Ammonium Acetate.

The diisopropyl ethyl ammonium acetate (DIPEAc)-promoted Biginelli protocol has been developed for the first time by a successive one-pot three-component reaction of aldehydes, ethylcyanoacetate/ethyl acetoacetate, and thiourea/urea to afford pharmacologically promising 1,2,3,4-tetrahydropyrimidines in high yields at room temperature. The key benefits of the present scheme are the capability to allow a variability of functional groups, short reaction times, easy workup, high yields, recyclability of the catalyst, and solvent-free conditions, thus providing economic and environmental advantages. In addition, a series of 4-oxo-6-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles analogues were synthesized and selected for their in vitro antifungal and antibacterial activities.

Synthesis and Antitubercular Activity of New Benzo[b]thiophenes.

In vitro and ex vivo efficacies of four series of benzo[b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo[b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A- and D-MDR-MTB/MTB (MIC ranges 2.73-22.86 µg/mL). The activity of all benzo[b]thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 µg/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo[b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-ß-d-ribose-2'-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand-protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis.

Ultrasound assisted one pot synthesis of imidazole derivatives using diethyl bromophosphate as an oxidant.

A one pot, three-component condensation of benzoin/benzyl, an aldehyde, and ammonium acetate using diethyl bromophosphate as a mild oxidant is achieved to form trisubstituted imidazole compounds. Under ultrasound irradiation, a smooth condensation occurs to get the 2, 4, 5-triaryl-1H-imidazole compounds in good to excellent yields. The study explores the scope and limitation of diethyl bromophosphate as an oxidant and suggests advantages, viz., simplicity of operation, reduction in time, and an increase in product yields.

Development of practical methodologies for the synthesis of novel 3(4-oxo-4H-chromen-3-yl)acrylic acid hydrazides.

We report a new environmentally-benign, convenient and facile methodology for the synthesis of new series of 3(4-oxo-4H-chromen-3-yl)acrylic acid hydrazides derivatives designed by exploring the molecular hybridization approach between isoniazide and 3(4-oxo-4H-chromen-3-yl)acrylic acids by using EDCl/HOBt under ultrasound irradiation in very short reaction time. Utilization of easy reaction conditions, isolation and purification makes this manipulation very interesting from an economic perspective.

Synthesis, analgesic and anti-inflammatory activities of some novel pyrazolines derivatives.

In search for a new analgesic and anti-inflammatory agent with improved potency, we designed and synthesized a series of 3,2-(4,5-dihydro-5-(4-morphilinophenyl)-1H-pyarazol-3-yl)phenols 6(a-g) and its N-phenylpyrazol-1-carbothioamide 7(a-g) by Claisan-Schmidt condensation followed by the reaction of hydrazine hydrate. All the synthesized compounds were assayed for their in vivo analgesic and anti-inflammatory activities. All the compounds synthesized showed the potential to demonstrate analgesic and anti-inflammatory activity, of particular interest compounds 6a, 6b, 6g, 7a, 7d and 7g were found comparable to Diclofenac.

Ultrasound assisted green synthesis of bis(indol-3-yl)methanes catalyzed by 1-hexenesulphonic acid sodium salt.

1-Hexenesulphonic acid sodium salt as catalyst for green synthesis of bis(indol-3-yl)methanes was described. The reaction of indole with various aldehydes in water using ultrasound irradiation at ambient temperature for appropriate time using 1-hexenesulphonic acid sodium salt furnish the desired product in good to excellent yield. Utilization of aqueous medium, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.

SAR study of clubbed [1,2,4]-triazolyl with fluorobenzimidazoles as antimicrobial and antituberculosis agents.

In the present study, a series of novel 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-1-substituted-4,6-difluoro-1H-benzo[d]imidazole derivatives are synthesized by the alkylation of 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-4,6-difluoro-1H-benzo[d]imidazole with substituted alkyl and aryl halides. The compounds were evaluated for their preliminary in-vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa and then were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. The antibacterial data suggested that the analogs with electronegative substituents emerged as promising antimicrobials. It was also observed that the promising antimicrobials have proved to be better antimycobacterials. Few of selected analogs are under further evaluation for secondary antitubercular screening, as they have shown better activity compared to rifampin.

Clubbed [1,2,3] triazoles by fluorine benzimidazole: a novel approach to H37Rv inhibitors as a potential treatment for tuberculosis.

A Novel Clubbed [1,2,3] triazoles with fluorine benzimidazole series of H37Rv strain inhibitors, potentially useful for the treatment of tuberculosis is disclosed on the basis of promising results of preliminary antimicrobial study. Evaluation of the SAR of substitution within these series has followed the identification of a range of compounds. Some of the derivatives are under further evaluation showing better considerable activity compared to rifampin.