Search results for "Cyclohexanes"
showing 10 items of 13 documents
Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer's amyloid precursor protein.
2017
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is the activation of G protein-coupled receptors (GPCRs). Therefore, our study aimed to analyze whether stimulation of angiotensin AT1 or AT2 receptors stably expressed…
The identification of vicinally substituted cyclohexane isomers in their mixtures by 1H and 13C NMR spectroscopy.
2000
The radical addition reactions of organobromine compounds, XBr (X = CH2COOMe, PhCH2, CHBr2 and CCl3) with cyclohexene afforded mixtures of cis/trans isomer pairs of 1-X-2-Br-cyclohexanes. In addition to benzyl benzoyloxy derivatives are formed also, when benzoyl peroxide is used as an initiator. Owing to the great difficulties in separating these cis/trans isomer pairs, they are identified directly in their mixtures by NMR spectroscopy. In addition to one-dimensional (ID) 1H, proton decoupled 13C and DEPT-135, also two-dimensional (2D) 13C-13C INADEQUATE as well as 1H-13C HMQC experiments have been used in assigning the signals of each compound in their mixtures. The identification of each …
The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment.
2011
Background: Cannabinoids are known to reduce intestinal inflammation. Atypical cannabinoids produce pharmacological effects via unidentified targets. We were interested in whether the atypical cannabinoid O-1602, reportedly an agonist of the putative cannabinoid receptor GPR55, reduces disease severity of dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6N and CD1 mice. Methods: DSS (2.5% and 4%) was supplied in drinking water for 1 week while TNBS (4 mg) was applied as a single intrarectal bolus. Results: Both treatments caused severe colitis. Injection of O-1602 (5 mg/kg intraperitoneally) significantly reduced macroscopic and histological col…
Comparison of some dispersion-corrected and traditional functionals as applied to peptides and conformations of cyclohexane derivatives.
2012
We compare the energetic and structural properties of fully optimized α-helical and antiparallel β-sheet polyalanines and the energetic differences between axial and equatorial conformations of three cyclohexane derivatives (methyl, fluoro, and chloro) as calculated using several functionals designed to treat dispersion (B97-D, ωB97x-D, M06, M06L, and M06-2X) with other traditional functionals not specifically parametrized to treat dispersion (B3LYP, X3LYP, and PBE1PBE) and with experimental results. Those functionals developed to treat dispersion significantly overestimate interaction enthalpies of folding for the α-helix and predict unreasonable structures that contain Ramachandran φ and …
Novel σ1 antagonists designed for tumor therapy: Structure – activity relationships of aminoethyl substituted cyclohexanes
2021
Abstract Depending on the substitution pattern and stereochemistry, 1,3-dioxanes 1 with an aminoethyl moiety in 4-position represent potent σ1 receptor antagonists. In order to increase the stability, a cyclohexane ring first replaced the acetalic 1, 3-dioxane ring of 1. A large set of aminoethyl substituted cyclohexane derivatives was prepared in a six-step synthesis. All enantiomers and diastereomers were separated by chiral HPLC at the stage of the primary alcohol 7, and their absolute configuration was determined by CD spectroscopy. Neither the relative nor the absolute configuration had a large impact on the σ1 affinity. The highest σ1 affinity was found for cis-configured benzylamines…
Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice.
2018
Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190540 También participan en la elaboración de este artículo científico: Aracely Calatayud-Pascual, Alicia López-Castellano, Elena P. Albelda, Enrique García-España, Luis Martí-Bonmatí, Juan C. Frias y M. Teresa Albelda. Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment.
Guest exchange in dimeric capsules formed by tetra-urea calix[4]arenes
2008
Ten tetra-urea calix[4]arene derivatives with different ether residues (methyl, pentyl, benzyl, all combinations of methyl and pentyl, 1,3-dibenzyl-2,4-dipentyl), including also the tetrahydroxy compound and the 1,3-dipentyl ether, were synthesised. Their urea groups were substituted with a lipophilic residue to ensure sufficient solubility in cyclohexane. Thus, kinetics for the exchange of the included guest (benzene) against the solvent (cyclohexane) could be followed by 1H NMR spectroscopy. The apparent first order rate constants decrease with increasing size of the ether residues from methyl to benzyl by more than three orders of magnitude. This can be understood by a decreasing flexibi…
In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /β2-adrenoceptor agonist (MABA) comp…
2019
Recent evidence indicates that AZD8999 (LAS190792), a novel muscarinic acetylcholine receptor antagonist and β2-adrenoceptor agonist (MABA) in development for chronic respiratory diseases, induces potent and sustained relaxant effects in human bronchi by adressing both muscarinic acetylcholine receptors and β2-adrenoceptor. However, the anti-inflammatory effects of the AZD8999 monotherapy or in combination with corticosteroids are unknown. This study investigates the anti-inflammatory effects of AZD8999 in monotherapy and combined with fluticasone propionate in neutrophils from healthy and chronic obstructive pulmonary disease (COPD) patients. Peripheral blood neutrophils from healthy and C…
Tailoring the stealth properties of biocompatible polysaccharide nanocontainers.
2014
Fundamental development of a biocompatible and degradable nanocarrier platform based on hydroxyethyl starch (HES) is reported. HES is a derivative of starch and possesses both high biocompatibility and improved stability against enzymatic degradation; it is used to prepare nanocapsules via the polyaddition reaction at the interface of water nanodroplets dispersed in an organic miniemulsion. The synthesized hollow nanocapsules can be loaded with hydrophilic guests in its aqueous core, tuned in size, chemically functionalized in various pathways, and show high shelf life stability. The surface of the HES nanocapsules is further functionalized with poly(ethylene glycol) via different chemistri…
Influence of Remote Substituents on the Equatorial/Axial Selectivity in the Monooxygenation of Methylene C−H Bonds of Substituted Cyclohexanes
2001
The reactivity of individual C--H bonds in the methyl(trifluoromethyl)dioxirane TFDO oxygenation of stereogenic methylene groups in conformationally homogeneous monosubstituted cyclohexanes (2) has been determined. The unexpectedly high occurrence of O-atom insertion into C--H(ax) bonds suggests an in plane trajectory attack in the oxygenation while the diastereoselectivity of the reaction is qualitatively interpreted on the basis of the distinct hyperconjugative stabilization by the substituent of diastereomeric transition states due to long-range through bond interactions.