Angel Rentería-Gómez

Synthesis of azepino[4,5-b]indol-4-ones via MCR/free radical cyclization and in vitro–in silico studies as 5-Ht6R ligands

A series of nine new 3-acetamide-azepino[4,5-b]indol-4-ones were synthesized in two steps: (i) multicomponent reaction (Ugi-4CR/SN2) and (ii) free radical-mediated cyclization. These compounds, along with their tetrazole-based analogs, were studied in vitro to assess their binding with the 5-hydroxytryptamine type 6 receptor (5-Ht6R). The 3-acetamide-azepino[4,5-b]indol-4-ones displayed moderate affinity, whereas the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones affinity values are lower. However, one of the 3-acetamide-azepino[4,5-b]indol-4-ones exhibited a hit value of Ki (211.2nM) to the 5-Ht6R. Minimal-energy structures of one cis-amide and its tetrazole-based analog (calculated by means of the Density Functional Theory) were analyzed to assess some interesting bioisosterism aspects. Interactions and binding energies between all products and the 5-Ht6R were calculated through in silico molecular couplings. Finally, a QSAR model was proposed using the results of the in vitro assays.

Synthesis of 2-julolidin-imidazo[1,2-a]pyridines via Groebke–Blackburn–Bienaymé reaction and studies of optical properties

A series of sixteen new 2-julolidin-imidazo[1,2-a]pyridine bound-type bis-heterocycles were synthesized in good to excellent yields (61–98%) via an MW-assisted Groebke–Blackburn–Bienayme (GBB) reaction. Then, experimental studies were conducted to determine the luminescence properties of these compounds. Various high quantum yields were found. In fact, one product exhibited a quantum yield (86.6%) comparable to that of the reference compound rhodamine (94.8%). Finally, further computational studies were performed by means of TD-DFT to calculate their HOMO–LUMO distributions and theoretical absorption spectra. A good agreement between the experimental and computational results was obtained, which provides a rationalized explanation for the observed structure/property relationships.

Synthesis of benzo-fused spiropiperidines through a regioselective free radical-mediated cyclization as key step: a suitable alternative towards the lead σ-1 receptor ligand L-687384

Abstract The synthesis of four novel benzo-fused spiropiperidines and the lead σ-1 receptor ligand L-687384 through a xanthate-mediated free radical spirocyclization as key step is described. Furthermore, the key free radical-based cyclization was computationally studied by means of the density functional theory approach at the UB3LYP/6-311+G(d) level to understand the regioselectivity because there are three possible closure pathways and only the benzo-fused spiropiperidines (ipso products) were experimentally found.Graphical abstract

Synthesis of 1′-tetrazolylmethyl-spiro[pyrrolidine-3,3′-oxindoles] via two coupled one-pot processes Ugi-azide/Pictet–Spengler and oxidative spiro-rearrangement

Six novel tris-heterocycles 1′-tetrazolylmethyl-spiro[pyrrolidine-3,3′-oxindoles] were synthesized in 39–82% yields in two experimental steps: (i) a one-pot Ugi-azide/Pictet–Spengler process coupled to (ii) a one-pot oxidative spiro-rearrangement. The synthesized polyheterocycles could be used for further in vitro studies because they contain moieties present in various anticancer bioactive molecules and drugs.

Solvent- and Catalyst-Free One-Pot Green Bound-Type Fused Bis-Heterocycles Synthesis via Groebke–Blackburn–Bienaymé Reaction/SNAr/Ring-Chain Azido-Tautomerization Strategy

A new, efficient, green, endogenous water-triggered, solvent- and catalyst-free ultrasound-assisted one-pot Groebke–Blackburn–Bienaymé reaction/SNAr/ring-chain azido-tautomerization strategy to synthesize bound-type fused bis-heterocycles imidazo or benzo[d]imidazo[2,1-b]thiazoles and 1,5-disubstituted tetrazole (1,5-DsT) containing quinoline moiety is described, which allows synthesis of two types of fused heterocycles in one step under mild green conditions. Antibacterial and antiamebic activities of selected newly synthesized compounds were carried out against three bacterial species: Gram-positive bacterium Staphylococcus aureus ATCC 6538 and Gram-negative bacteria Pseudomonas aeruginosa ATCC 13384 and Escherichia coli O55 and against one amebic species: Entamoeba histolytica.

Synthesis of 1,5-disubstituted tetrazoles containing propargyl moiety

A series of nine new 1,5-disubstituted-1H-tetrazoles were synthesized via MCR Ugi-azide in moderate to excellent yields (80 - 95%), using propargyl amine as component varying the aldehyde and isocyanide components. 1,5-DS-T are useful heterocyclic moieties present in many bioactive compounds and drugs. Morever 1,5-DS-T are used as bidentate ligands, in coordination chemistry, metal-organic framework science, bioimaging, photo-imaging, explosives, propellants, high energy materials.

In vitro and in silico evaluation of twelve newly-synthesized 1-acetamide-5-methoxy-2-oxindoles as 5-Ht7 receptor ligands

Based on in vitro studies of twelve newly-synthesized 1-acetamide-5-methoxy-2-oxindoles as 5-Ht7 receptor ligands, Structure Affinity Relationship (SAR) and Quantitative Structure Affinity Relationship model (QSAR) are provided. Also, a ligand-based pharmacophore model is proposed through molecular docking techniques and Nucleus Independent Chemical Shift DFT calculations (NICS).