Micellar photocatalysis enables divergent C-H arylation and N dealkylation of benzamides via N-acyliminium cations

Micellar photocatalysis has recently opened new avenues to activate strong carbon halide bonds. So far, however, it has mainly explored strongly reducing conditions restricting the available chemical space to radical or anionic reactivity. Here, we demonstrate a radical-polar crossover process involving cationic intermediates, which enables chemodivergent modification of chlorinated benzamide derivatives via either C H arylation or N dealkylation. The catalytic system operates under mild conditions employing methylene blue as a photocatalyst and blue LEDs as the light source. Factors determining the reactivity of substrates and preliminary mechanistic studies are presented.

Synthesis of C,N,N-Cyclometalated Gold(III) Complexes with Anionic Amide Ligands

A series of neutral C,N,N Au(III) complexes was synthesized with N-(8-quinolinyl)benzamide derivatives and chiral N-(2-(oxazolin-2-yl)phenyl)benzamide derivatives. This convenient synthesis method for amide ligands as well as an operationally simple complexation by direct C-H auration permitted changes to both the steric and electronic properties of the Au(III) complexes for promoting catalytic three-component coupling of an aldehyde, an amine, and an alkyne.

Cytotoxic and antitumoral activity of N-(9H-purin-6-yl) benzamide derivatives and related water-soluble prodrugs

Background: The development of small molecules as cancer treatments is still of both interest and importance. Objective: Having synthesized and identified the initial cytotoxic activity of a series of chemically related N-(9H-purin-6-yl) benzamide derivatives, we continued their evaluation on cancer cell models. We also synthesized water-soluble prodrugs of the main compound and performed in vivo experiments. Method: We used organic chemistry to obtain compounds of interest and prodrugs. The biological evaluation included MTT assays, synergy experiments, proliferation assays by CFSE, cell cycle distribution and in vivo antitumoral activity. Results: Our results show activities on cancer cell lines ranging from 3-39 µM for the best compounds, with both induction of apoptosis and decrease in cell proliferation. Two compounds evaluated in vivo showed weak antitumoral activity. In addition, the lead compound and its prodrug had a synergistic activity with the nucleoside analogue fludarabine in vitro and in vivo. Conclusion: Our work allowed us to gain better knowledge on the activity of N-(9H-purin-6-yl) benzamide derivatives and showed new examples of water-soluble prodrugs. More research is warranted to decipher the molecular mechanisms of the molecules.

Designing of some Novel Methyl 2-((4-(Benzamido)Phenyl)Sulfanyl)-1,2,3,4-tetrahydro-6-Methylpyrimidine-5-carboxylate Derivatives as Potential Glucokinase Activators through Molecular Docking

Aims: Glucokinase (GK) is a cytoplasmic enzyme that metabolizes the glucose to glucose- 6-phosphate and supports the adjusting of blood glucose levels within the normal range in humans. In pancreatic β-cells, it plays a leading role by governing the glucose-stimulated secretion of insulin and in liver hepatocyte cells, it controls the metabolism of carbohydrates. GK acts as a promising drug target for the treatment of patients with type 2 diabetes mellitus (T2DM). Study Design: In the current study, the goal is to identify new substituted benzamide derivatives and test them via molecular docking as possible anti-diabetic drugs. Place and Duration of Study: The present work has been carried out at S.N.J.B’s S.S.D.J. College of Pharmacy, Neminagar, Chandwad, Nashik, Maharashtra, India during the time period of December-2020 to February-2021. Methodology: This work involved designing novel methyl 2-((4-(benzamido)phenyl)sulfanyl)-1,2,3,4-tetrahydro-6-methylpyrimidine-5-carboxylate derivatives and their screening by molecular docking studies to determine the binding interactions for the best-fit conformations in the binding site of the GK enzyme. Autodockvina 1.1.2 in PyRx 0.8 was used to perform the docking studies of all the designed novel derivatives and native ligand against the crystal structure of GK. Based on the results of docking studies, the selected molecules will be tested for their antidiabetic activity in the animal models. Results: Amongst the designed derivatives, compounds A2, A3, A8, A10, A11, A13, A14, A16, A17, and A18 have shown better binding free energy (between -8.7 to -10.3 kcal/mol) than the native ligand present in the enzyme structure. In present investigation, many molecules had formed strong hydrogen bond with Arg-63 which indicate the potential to activate GK. Conclusion: From above results it has been observed that these designed benzamide derivatives have potential to activate the human GK which enables us to proceed for the syntheses of these derivatives.