Design, Synthesis and Antidiabetic Activity of Novel Pyrrole-3-Carboximidamide Derivatives as Dipeptidyl Peptidase-4 Inhibitors.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as an effective therapeutic option. A new series of pyrrole-3-carboximidamide derivatives was designed, synthesized, and evaluated as DPP-4 inhibitors. Most of the synthesized compounds exhibited favorable inhibitory activity against the DPP-4 enzyme, and compounds 5f and 5g were found to be the most potent inhibitors with IC₅₀ values of 12.

Synthesis of 4-tosyl quinazoline derivatives with the assistance of ultrasound irradiation as a guide to the reaction pathway.

In this study, we tried to show the role of ultrasonic waves in the reaction pathway of quinazolines with an amide functional group. At first, 4-tosyl quinazolines were prepared using a simple, rapid, and one-pot reaction of Cu-catalyzed cross-coupling reactions of 2-iodoaniline and tosyl methyl isocyanide (TosMIC) in THF solvent under ultrasonic conditions in 30 min with good efficiency. The role of ultrasound in this reaction is to reduce the time and increase the efficiency of product preparation.

Synthesis, Molecular Dynamics Simulation, and Antitumor Activity of Quinazoline-2,4,6-triamine Derivatives as Novel EGFR Tyrosine Kinase Inhibitors.

Background: Developing a potent and safe scaffold is challenging in anti-cancer drug discovery.

Objectives: The study focused on developing novel series of compounds based on the inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) as one of the most promising compounds in cancer therapy.

Methods: In this study, a novel series of quinazoline-2,4,6-triamine derivatives were designed and synthesized through intramolecular C-H activation reaction of -nitro aniline, trichloroacetonitrile, and isocyanides employing a one-pot reaction.

Targeting EGFR Tyrosine Kinase: Design, Synthesis and Biological Evaluation of Novel Quinazolinone Derivatives.

Impaired cell cycle regulation and disturbance in signal transduction pathway are two major causes of a condition defined as cancer, one of the significant reasons for mortality worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been commonly used as anticancer agents, and the majority of this medications possess quinazoline moiety as a heteroaromatic core. In this study, two novel series of EGFR-TKIs containing quinazolinone core were designed and synthesized.

Synthesis of 4,6-diphenylpyrimidin-2-ol derivatives as new benzodiazepine receptor ligands.

Benzodiazepines (BZDs) have been widely used in neurological disorders such as insomnia, anxiety, and epilepsy. The use of classical BZDs, e.g.

Design, synthesis, and pharmacological evaluation of novel 1,2,4-triazol-3-amine derivatives as potential agonists of GABA subtype receptors with anticonvulsant and hypnotic effects.

In the current study, a series of novel 1,2,4-triazol-3-amine derivatives were designed, synthesized, and biologically evaluated in vivo for their anticonvulsant and hypnotic effects in the pentylenetetrazole (PTZ)-induced seizures, maximal electroshock (MES)-induced seizures, and pentobarbital-induced sleeping tests. Furthermore, the possible side effects of the most potent compounds on the memory, motor coordination, and muscle strength were evaluated in passive avoidance, rotarod, and grip strength tests, respectively. The designed compounds with the main benzodiazepine pharmacophores including aromatic ring and proton accepting group completely mimiced the structure of zolpidem as an α1-selective agonist of GABA receptor.

Ultrasound-assisted synthesis of highly functionalized benzo[1,3]thiazine via Cu-catalyzed intramolecular CH activation reaction from isocyanides, aniline-benzoyl(acetyl) isothiocyanate adduct.

A facile sonochemical route for the synthesis of benzo[1,3]thiazine derivatives via a one pot, multicomponent, intramolecular CH activation reaction from isocyanides, aniline and benzoyl (acetyl) isothiocyanate adduct catalyzed by copper (I) iodide in acetone at 30 °C have been reported. The advantages of the described method include using simple and readily available starting materials and performing under mild copper-catalytic reaction conditions and also obtaining pure product with high yield without applying column chromatography. Furthermore, using the sonochemical methodology as an efficient method led to reduce the reaction times.

A direct access to heptasubstituted biguanides.

An efficient and experimentally simple copper-catalyzed carbon-nitrogen bond formation for the synthesis of [Formula: see text]-arylated biguanides starting from aryl halides, carbodiimides, and 1,1,3,3-tetramethylguanidine is reported. The potential diversity of this type of reaction, easily available starting materials, and commercially available low-cost catalysts are the incremental features of this methodology.

A tandem synthesis of 5-sulfonylimino-2-imidazolones from sulfonoketenimides and dialkyl azodicarboxylates.

Functionalized 5-sulfonylimino-2-imidazolones are prepared by a copper-catalyzed reaction of dialkyl azodicarboxylates with sulfonoketenimides, generated from terminal alkynes and sulfonyl azides, in good to excellent yields.

Sulfonoketenimides as key intermediates for the synthesis of 2-thioxo-2H-1,3-thiazines and 2-arylimino-2H-1,3-thiazines.

The synthesis of a novel class of highly functionalized 1,3-thiazine derivatives via a copper-catalyzed tandem reaction of 1,1,3,3-tetramethylguanidine, [Formula: see text], sulfonyl azides, and terminal alkynes is described. Using isothiocyanates as the heterocumulene component, affords 2-arylimino-1,3-thiazine derivatives in moderate to good yields.

A tandem synthesis of functionalized azet-2(1H)-ones and azet-2(1H)-thiones.

Highly functionalized azet-2(1H)-ones and azet-2(1H)-thiones are obtained via a copper-catalyzed tandem reaction of readily available terminal alkynes, sulfonyl azides, and heterocummulenes in moderate to good yields.

Tandem synthesis of highly functionalized pyrazole derivatives from terminal alkynes, sulfonyl azides, diethyl azadicarboxylate, and sodium arylsulfinates.

The reaction between ketenimine intermediates [generated from terminal alkynes and sulfonyl azides], diethyl azadicarboxylate, and sodium arylsulfinates in N, N-dimethylformamide at room temperature, affords ethyl 2,3-dihydro-3-oxo-4-phenyl-2-tosyl-5-(tosylamino)pyrazole-1-carboxylates in moderate-to-good yields. When diisopropyl azadicarboxylate was used as the ester component, diisopropyl 1-arylsulfonyl-2-{[aryl(alkyl)sulfonyl]-2-phenylethanimidoyl}-1,2-hydrazinedicarboxylates were obtained.

A synthesis of phosphorylated dioxohexahydropyrimidines from N,N'-dimethylurea, activated acetylenes, and trialkyl phosphites.

An efficient synthesis of alkyl 5-(dialkoxy- phosphoryl)-1,3-dimethyl-2, 6-dioxo-hexahydropyrimidine-4-carboxylates is described. This involves the reaction of N,N'-dimethylurea and dialkyl acetylendicarboxylates in the presence of trialkyl phosphites. Under similar conditions, triphenyl phosphite led to alkyl 5-(diphenoxyphosphoryl)-1,3-dimethyl-2,6-dioxo-hexahydro-4-pyrimidinecarboxylates.