Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.

This work involves the synthesis and subsequent development of a number of novel organocatalysts generated from β-amino acids bearing diendo and diexo norbornene skeletons to improve their catalytic characteristics.

Derivatives of the new ring system benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepinone and its cycloalkane and cycloalkene condensed analogues have been conveniently synthesized through a three-step reaction sequence. An atom-economical, one-pot, three-step cascade process engaging five reactive centers (amide, amine, carbonyl, azide, and alkyne) has been performed for the synthesis of alicyclic derivatives of quinazolinotriazolobenzodiazepine using cyclohexane, cyclohexene, and norbornene β-amino amides. The stereochemistry and relative configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy and X-ray crystallography. The reaction was also performed using enantiomeric starting materials leading to enantiomeric quinazolinotriazolobenzodiazepine with an ee of 95%. The synthesis of 9H-benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepinone, a new heterocyclic system, was achieved in a good yield using a retro Diels–Alder (RDA) procedure. Some compounds were tested for antiproliferative activities against five human cancer cell lines of gynecological.

Reactions of diastereochemically varied norbornene-condensed 2-thioxopyrimidin-4-ones 6 and 10 with variously functionalized hydrazonoyl chlorides 2a–h gave regioselectively angular norbornene-based [1,2,4]triazolo[4,3-a]pyrimidin-7(1H)-ones 7a–h and 11a,c–e, respectively. Thermal retro Diels–Alder (RDA) reaction of 7a–h and 11a,c–e resulted in the target compounds 4a–h as single products. On the other hand, reactions of thiouracil 1 and hydrozonoyl chlorides 2a–e gave regioselectively [1,2,4]triazolo[4,3-a]pyrimidinone-5(1H)-ones 3a–e. The opposite regioselectivity of thiouracil 1 and norbornene-condensed 2-thioxopyrimidin-4-ones 6 and 10 was attributed to electronic factors according to DFT calculations. The angular structure of norbornene based [1,2,4]triazolo[4,3-a]pyrimidin-7(1H)-ones was confirmed by single crystal X-ray crystallography.

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ee_s > 62% and ee_p > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H₂O extraction.