Examinando por Autor "Recio, Javier"

Mostrando 1 - 9 de 9

A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis
(Elsevier, 2020-06-17) Bazan, Hernan A.; Bhattacharjee, Surjyadipta; Burgos, Carolina; Recio, Javier; Abet, Valentina; Pahng, Amanda R.; Jun, Bokkyoo; Heap, Jessica; Ledet, Alexander J.; Gordon, William C.; Edwards, Scott; Paul, Dennis; Alvarez-Builla, Julio; Bazan, Nicolas G.
Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity. 1 is a non-hepatotoxic, metabolically unstable lipophilic ApAP analog that is not antipyretic. The newly synthesized 3 is a non-hepatotoxic ApAP analog that is stable, lipophilic, and retains analgesia and antipyresis. Intraperitoneal or po administration of the new chemical entities (NCEs), 3b and 3r, in concentrations equal to a toxic dose of ApAP did not result in the formation of NAPQI. Unlike livers from NCE-treated mice, the livers from ApAP-treated mice demonstrated large amounts of nitrotyrosine, a marker of mitochondrial free radical formation, and loss of hepatic tight junction integrity. Given the widespread use of ApAP, hepatotoxicity risk with overuse, and the ongoing opioid epidemic, these NCEs represent a novel, non-narcotic therapeutic pipeline.
Access to 2-substituted 1-pyridin-3-yl-β-carboline derivatives by intramolecular radical cyclization-ring opening-SNAr substitution
(ROYAL SOC CHEMISTRY, 2019-08-08) Recio, Javier; Perez-Redondo, Adrian; Alvarez-Builla, Julio; Burgos, Carolina
A new method for the synthesis of 1-pyridin-3-yl-β-carboline derivatives involving an intramolecular radical reaction in the presence of tris(trimethylsilyl)silane and azobisisobutyronitrile (TTMSS/AIBN), via a sultam intermediate, which proceeds as a one-pot process by ring opening and SNAr substitution, is described.
Highly efficient unbridged D-A+(D) chromophores based on the quinolizinium cation for nonlinear optical (NLO) applications.
(Elsevier, 2022-04-14) Sánchez-Pavón, Esmeralda; Recio, Javier; Ramirez, Marco Antonio; Batanero, Belen; Clays, Koen; Mendicuti, Francisco; Marcelo, Gema; Carmona, Thais; Castaño, Obis; Angelova, Silvia; Andres, Jose L.; Vaquero, Juan J.; Cuadro, Ana M.
Novel charged D-A+ chromophores based on quinolizinium cations as acceptor unit have been prepared by treating haloquinolizinium salts with N-heteroarylstannanes under Stille reaction conditions. This approach provides an easy access to potential one-dimensional D-A+ and two-dimensional D-A+-D chromophores in which the acceptor moiety (A+) is the simple azonia cation and the donors are different π-rich N-heterocycles. The first hyperpolarizabilities (β) were measured by hyper-Rayleigh scattering experiments and the experimental data confirmed that the inherent polarization between donor and acceptor fragments modulates the NLO properties. The electronic structures and properties (including both the linear and nonlinear optical properties) of the quinolizinium chromophores were examined by theoretical (DFT, HF and MP2) calculations. A promising strategy for the rational design of D-A building blocks to create new organic-based NLO materials is proposed.
Microwave-assisted conversion of carbonyl compounds into formylated secondary amines: new contribution to the Leuckart reaction mechanism in N-methylformamide
(ELSERVIER, 2013-04-03) Barba, Fructuoso; Recio, Javier; Batanero, Belen
The reductive amination of several carbonyl compounds (Leuckart reaction) has been performed using Nmethylformamide and microwave technology. Under these conditions, a new mechanism is proposed via the initial formation of an imine, followed by reduction to the amine by ‘in situ’ generated formic acid, and further formylation of the amine. Using this methodology, the formyl derivatives of several secondary amines were obtained in good to excellent yields.
One-pot anodic lactonization of Fenchone and Menthone and electrosynthesis of a new magnolione analogue
(ELSERVIER, 2016-05-25) Batanero, Belen; Recio, Javier; Barba, Fructuoso
The terpenoid cycloalkanones Fenchone and Menthone have been oxidized at a platinumanode under neutral and alkaline electrolyte conditions. When NaClO4 was used as electrolyte, Fenchone (1a) afforded 1-isopropyl-4- methyl-2-oxa-bicyclo[2.2.1]heptan-3-one, and Menthone (1b) provided the stable lactone 6-isobutyl-4- methyl-tetrahydropyran-2-one, both in good yield.When using Na2CO3 as electrolyte, the oxidation of 1a gave the fragrance-analogue 2,2-dimethyl-3-(2-oxopropyl) cyclopentanone in only one-pot. Mechanism proposals are presented.
Studies on the preparation of aminobipyridines and bipyridine sultams via an intramolecular free radical pathway
(ROYAL SOC CHEMISTRY, 2020-03-04) Recio, Javier; Filace, Fabiana; Gala, Elena; Pérez-Redondo, Adrián; Álvarez-Builla, Julio; Burgos, Carolina
A variety of aminated bipyridines and bipyridine sultams are prepared by intramolecular radical [1,5]-ipso and [1,6]-ortho substitutions, using a sulfonamide as a linker to connect the pyridyl radical to the pyridine under attack. For the cases studied, different regiochemistries are observed depending on the initial position of the sulfonamide linker.
Synthesis of Florbetapir aza-analogues using chemistry of pyridinium N-aminides
(ARKAT USA, 2021-12-17) Gala, Elena; Recio, Javier; Álvarez-Builla, Julio; Izquierdo, M.Luisa
Neuroimaging of β-amyloid (Aβ) plaques in brain, employing Positron Emission Tomography (PET) has enabled early diagnosis of Alzheimer’s Disease and, although different 18F radiolabeled markers as Florbetapir and Florbetaben are already in the market, new molecules with better affinity and selectivity to Aβ plaques should be explored. In this article, two aza-analogues of Florbetapir have been synthesized from Pyridinium N-aminides. The new aza-analogues were prepared following straightforward synthetic routes under mild conditions. Although the products have been obtained using stable 19F, the methods are compatible with the future use of 18F, to generate products to be tested in the development of new PET reagents.
The emerging role of mixed lineage kinase 3 (MLK3) and its potential as a target for neurodegenerative diseases therapies
(ELSERVIER, 2023-05-24) Moreno, Ricardo; Recio, Javier; Barber, Santiago; Gil, Carmen; Martinez, Ana
Selective and brain-permeable protein kinase inhibitors are in preclinical development for treating neurodegenerative diseases. Among them, MLK3 inhibitors, with a potent neuroprotective biological action have emerged as valuable agents for the treatment of pathologies such as Alzheimer’s, Parkinson’s disease and amyotrophic lateral sclerosis. In fact, one MLK3 inhibitor, CEP-1347, reached clinical trials for Parkinson’s disease. Additionally, another compound called prostetin/12k, a potent and rather selective MLK3 inhibitor has started clinical development for ALS based on its motor neuron protection in both in vitro and in vivo models. In this review, we will focus on the role of MLK3 in neuron-related cell death processes, neurodegenerative diseases, and the potential advantages of targeting this kinase through pharmacological modulation for neuroprotective treatment.
Two-photon activated precision molecular photosensitizer targeting mitochondria
(Nature Research, 2021-10-07) Santiago, Ana M.; Mariz, Inês F. A.; Pinto, Sandra N.; Martinho, José M. G.; Recio, Javier; Vaquero, Juan J.; Cuadro, Ana M.; Maçôas, Ermelinda
Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.