Search results for "Amidine"
showing 10 items of 60 documents
New Strategies for the Synthesis of Fluorinated Vinylogous Amidines and β-Enamino Ketones
2001
Reaction of fluorinated imidoyl chlorides 3 with ketimines 1a provides fluorinated 1,3-diimines, which were exclusively isolated as vinylogous amidine tautomers 2beta, with good yields. Fluorinated beta-enamino ketones 4 are obtained by regioselective hydrolysis of 2. Complementary methods for the synthesis of regioisomeric beta-enamino ketones 4 and 5 are also reported. These methods include the reaction of azaenolates of ketimines with fluorinated esters 6 and reactions of ketone enolates with fluorinated imidoyl chlorides 3. The behavior of these systems in hydrolysis reactions was also tested.
“Click” on PLGA-PEG and hyaluronic acid: Gaining access to anti-leishmanial pentamidine bioconjugates
2017
Pentamidine (Pent), an antiparasitic drug used for the treatment of visceral leishmaniasis, has been modified with terminal azide groups and conjugated to two different polymer backbones (PLGA-PEG [PP] copolymer and hyaluronic acid [HA]) armed with alkyne end-groups. The conjugation has been performed by Copper Catalyzed Azido Alkyne Cycloaddition (CuAAC) using CuSO4 /sodium ascorbate as metal source. The novel PP-Pent and HA-Pent bioconjugates are proposed, respectively, as non-targeted and targeted drug delivery systems against Leishmania infections. Moreover, Pent has been encapsulated into PP nanoparticles by the oil-in-water emulsion method, with the aim to compare the biological activ…
Imidazolsynthesen, Mitt. Synthese α-substituierter 4(5)-Methoxymethyl-5(4)-methyl-imidazole
1977
Methoxymercurierung der α,β-ungesattigten Ketone 1 ergibt α-Acetoxymercuri-β-methoxy-ketone 2, die direkt zu α-Brom-β-methoxy-ketonen 3 bromo- demercuriert werden. Cyclisierung von 3 mit Formamidinacetat in flussigem Ammoniak fuhrt zu α-substituierten 4(5)-Methoxy-methyl-5(4)-methyl-imidazolen 4, deren Struktur 13C-NMR-spektroskopisch gesichert ist. Synthesis of α-Substituted 4(5)-Methoxymethyl-5(4)-methylimidazoles Methoxymercuration of the α,β-unsaturated ketones 1 produces the α-acetoxymercury-β-methoxyketones 2, which are bromo-demercurised without isolation to give the α-bromo-β-methoxyketones 3. Cyclisation of 3 with formamidine acetate in liquid ammonia leads to α-substituted 4(5)-me…
Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt
2020
A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency.
"Click" on PLGA-PEG and hyaluronic acid: gaining access to anti-leishmanial pentamidine bioconjugates
2018
Pentamidine (Pent), an antiparasitic drug used for the treatment of visceral leishmaniasis, has been modified with terminal azide groups and conjugated to two different polymer backbones (PLGA-PEG [PP] copolymer and hyaluronic acid [HA]) armed with alkyne end-groups. The conjugation has been performed by Copper Catalyzed Azido Alkyne Cycloaddition (CuAAC) using CuSO4/sodium ascorbate as metal source. The novel PP-Pent and HA-Pent bioconjugates are proposed, respectively, as non-targeted and targeted drug delivery systems against Leishmania infections. Moreover, Pent has been encapsulated into PP nanoparticles by the oil-in-water emulsion method, with the aim to compare the biological activi…
In vitro evaluation of glycol chitosan based formulations as oral delivery systems for efflux pump inhibition.
2017
Recently, we have reported that glycol chitosan (GCS) was able to reverse the P- glycoprotein (P-gp) efflux pump. The objective of the present study was to evaluate the potential of two GCS-based dosage forms (aqueous solution or nanoparticle suspension) for oral administration of the P-gp substrate Rho-123. A further aim of the present study was to assess the effect of the glycol chitosan-4-thiobutylamidine thiomer (GCS-TBA) on P-gp activity considering that the corresponding thiomer of chitosan series is a well-known P-gp inhibitor. Pre-treatment of Caco-2 cell monolayer with a GCS solution or GCS-based nanoparticles increased the absorptive transport of Rho-123 across the monolayer of 1.…
Neurochemistry of identified motoneurons of the tensor tympani muscle in rat middle ear
2008
The objective of the present study was to identify efferent and afferent transmitters of motoneurons of the tensor tympani muscle (MoTTM) to gain more insight into the neuronal regulation of the muscle. To identify MoTTM, we injected the fluorescent neuronal tracer Fluoro-Gold (FG) into the muscle after preparation of the middle ear in adult rats. Upon terminal uptake and retrograde neuronal transport, we observed FG in neurons located lateral and ventrolateral to the motor trigeminal nucleus ipsilateral to the injection site. Immunohistochemical studies of these motoneurons showed that apparently all contained choline acetyltransferase, demonstrating their motoneuronal character. Different…
Role of the cyclic AMP-dependent pathway in free radical-induced cholesterol accumulation in vascular smooth muscle cells.
2000
We have previously reported that free radical-treated vascular smooth muscle cells (SMC) lead to cholesterol accumulation in vitro. In the current study, we investigated the effects of oxidative stress on cyclic AMP concentration and cAMP-dependent enzymes involved in cholesterol homeostasis in A7r5 cells. Under our conditions of a mild oxidative stress, namely with no change in cell viability, we found that free radicals, initiated using azobis-amidinopropane dihydrochloride (AAPH), resulted in a dose-dependent decrease in cellular cAMP which was opposed by vitamin E preincubation. Although the addition of adenylate cyclase activators (carbacyclin and forskolin) increased cAMP levels it di…
Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells.
1999
The transformation of macrophages and smooth muscle cells into foam cells by modified low-density lipoproteins (LDL) is one of the key events of atherogenesis. Effects of free radicals have mainly been studied in LDL, and other than toxicity, data dealing with direct action of free radicals on cells are scarce. This study focused on the direct effects of free radicals on cholesterol metabolism of smooth muscle cells. A free radical generator, azobis-amidinopropane dihydrochloride, was used, and conditions for a standardized oxidative stress were set up in vascular smooth muscle cells. After free radical action, the cells presented an accumulation of cholesterol that appeared to be the resul…
Application of Molecular Topology for the Prediction of Reaction Yields and Anti-Inflammatory Activity of Heterocyclic Amidine Derivatives
2011
Topological-mathematical models based on multiple linear regression analyses have been built to predict the reaction yields and the anti-inflammatory activity of a set of heterocylic amidine derivatives, synthesized under environmental friendly conditions, using microwave irradiation. Two models with three variables each were selected. The models were validated by cross-validation and randomization tests. The final outcome demonstrates a good agreement between the predicted and experimental results, confirming the robustness of the method. These models also enabled the screening of virtual libraries for new amidine derivatives predicted to show higher values of reaction yields and anti-infl…