The present study describes the synthesis of an analog of the anti‐inflammatory drug fenbufen, a compound which has recently attracted of renewed interest in the treatment of chronic degenerative diseases such as cancer and rheumatoid arthritis. The molecule under consideration, 4‐(4‐methoxyphenyl)‐4‐oxobutanoic acid, is distinguished from fenbufen by the absence of the biphenyl moiety. This characteristic results in the generation of nontoxic metabolites during biotransformation. The incorporation of aromatic amino acid residues (phenylalanine and tyrosine) led to the modulation of the hybrid NSAID–amino acid and NSAID–peptide derivatives, thereby altering their biological activity and safety profile. The inhibitory activity against the dual cyclooxygenase‐2/5‐lipoxygenase system was evaluated using molecular docking, free energy calculations, and per‐residue decomposition analysis based on molecular dynamics simulations. Compounds containing a tyrosine residue or the Tyr‐Phe dipeptide exhibited strong drug–receptor binding affinities and long‐term stability during our simulations, in some cases outperforming the reference drugs celecoxib and zileuton. The values of the free energy (Δ G ) obtained through the Boltzmann equation demonstrated a strong correlation with the energy decomposition data, particularly for the lead compounds, which exhibited stabilizing interactions with the heme prosthetic group and the Fe ²⁺ ion. These findings provide substantial support for the identification of these molecules as promising candidates for further preclinical development.

The mixture of enantiomers in pharmaceuticals can lead to adverse effects, as demonstrated by thalidomide, where one enantiomer exhibited therapeutic properties while the other was teratogenic. Currently, efforts are focused on developing efficient catalysts capable of selectively producing a single stereoisomer, particularly in the synthesis of neuropharmaceuticals and NSAIDs. In this context, a new chiral catalyst was synthesized, featuring a palladium core and the dipeptide L-lysine-glycine as a ligand. The catalyst was characterized using various spectroscopic techniques and exhibited enantiomeric excesses of up to 40% in aldol reactions. Additionally, it efficiently promoted Heck cross-coupling reactions, indicating its potential catalytic versatility.

The induction of chirality to obtain enantiopure products of high synthetic value is of great importance across various scientific fields, particularly in the medical area, as it has been demonstrated that the different enantiomers of drugs interact differently with biological receptors. In this context, asymmetric catalysis focuses on the design of catalysts that are easy to synthesize, capable of efficiently and enantioselectively forming C–C bonds, and suitable for reuse in multiple catalytic processes. This work describes the application of a Pd(II) complex coordinated with the R and S forms of proline in direct Aldol, Morita–Baylis–Hillman, and Heck coupling reactions. The catalytic system efficiently promoted the aldol reaction, achieving yields of 80–95%, excellent diastereoselectivities (1:69 syn/anti), and enantiomeric excesses greater than 99%. From a mechanistic perspective, the formation of a transition state is proposed in which a proline molecule generates an enamine that, upon coordination with the metal center, is stabilized through interaction with the intermediate’s double bond. Moreover, the study of the Morita–Baylis–Hillman and Heck coupling reactions highlights the versatility of this type of catalyst.