Synthesis of steroid–ferrocene conjugates of steroidal 17-carboxamides via a palladium-catalyzed aminocarbonylation – Copper-catalyzed azide–alkyne cycloaddition reaction sequence

Szánti-Pintér, Eszter; Balogh, János; Csók, Zsolt; Kollár, László; Gömöry, Ágnes; Skoda‐Földes, Rita

doi:10.1016/j.steroids.2011.07.006

Cited by 21 publications

(19 citation statements)

References 41 publications

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“…The steroid compound C1 was synthesized by a method, which was described earlier in details ( Horváth et al, 2011 ; Szánti-Pintér et al, 2011 , 2015 ). In brief, the 16-keto-18-nor-13α-steroid was obtained via an unusual Wagner–Meerwein rearrangement of 16α,17α-epoxy-5α-androstane in the presence of an imidazolium-based ionic liquid ( Horváth et al, 2011 ).…”

Section: Methodsmentioning

confidence: 99%

Antinociceptive Effects of Lipid Raft Disruptors, a Novel Carboxamido-Steroid and Methyl β-Cyclodextrin, in Mice by Inhibiting Transient Receptor Potential Vanilloid 1 and Ankyrin 1 Channel Activation

et al. 2020

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Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons, and play an integrative role in pain processing and inflammatory functions. Lipid rafts are liquid-ordered plasma membrane microdomains rich in cholesterol, sphingomyelin, and gangliosides. We earlier proved that lipid raft disintegration by cholesterol depletion using a novel carboxamido-steroid compound (C1) and methyl β-cyclodextrin (MCD) significantly and concentration-dependently inhibit TRPV1 and TRPA1 activation in primary sensory neurons and receptor-expressing cell lines. Here we investigated the effects of C1 compared to MCD in mouse pain models of different mechanisms. Both C1 and MCD significantly decreased the number of the TRPV1 activation (capsaicin)-induced nocifensive eye-wiping movements in the first hour by 45% and 32%, respectively, and C1 also in the second hour by 26%. Furthermore, C1 significantly decreased the TRPV1 stimulation (resiniferatoxin)-evoked mechanical hyperalgesia involving central sensitization processes, while its inhibitory effect on thermal allodynia was not statistically significant. In contrast, MCD did not affect these resiniferatoxin-evoked nocifensive responses. Both C1 and MCD had inhibitory action on TRPA1 activation (formalin)-induced acute nocifensive reactions (paw liftings, lickings, holdings, and shakings) in the second, neurogenic inflammatory phase by 36% and 51%, respectively. These are the first in vivo data showing that our novel lipid raft disruptor carboxamidosteroid compound exerts antinociceptive and antihyperalgesic effects by inhibiting

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Section: Methodsmentioning

confidence: 99%

Antinociceptive Effects of Lipid Raft Disruptors, a Novel Carboxamido-Steroid and Methyl β-Cyclodextrin, in Mice by Inhibiting Transient Receptor Potential Vanilloid 1 and Ankyrin 1 Channel Activation

et al. 2020

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“…2 ). Aminocarbonylation reaction of 17-iodo-5α-androst-16-ene ( 2 ) in the presence of prop-2-yn-1-amine led to steroidal carboxamide C2 of the natural androstane series ( 68 ).…”

Section: Methodsmentioning

confidence: 99%

Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation

Sághy

Payrits

Bíró-Sütő

et al. 2018

Journal of Lipid Research

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Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons. These thermosensor channels play a role in pain processing. We have provided evidence previously that lipid raft disruption influenced the TRP channel activation, and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or whether altered position of the carboxamido group (C2) influences the inhibitory action by measuring Ca2+ transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarization by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca2+ enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarization. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential.

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“…During the last few years significant advances have been achieved in the development of cross-coupling methods for the synthesis of different classes of aromatic carbonyl compounds. Transition metal-catalyzed carbonylation of aryl halides in the presence of nucleophiles is an efficient method for the preparation of such compounds [1]. Amides, as an important subgroup of carbonyl compounds, are widely used in medicinal chemistry [2].The introduction of a carboxamide moiety into a skeleton of practical importance, via simple homogeneous catalytic methods, is of high interest [1,2,3].There are a number of applications for both the synthesis of simple building blocks and for the functionalization of biologically important skeletons [4,5].…”

Section: Introductionmentioning

confidence: 99%

Aminocarbonylation Reaction Using Palladium Complexes Containing Phosphorus-Nitrogen Ligands as Catalysts

Apanda

Zolezzi

Valdebenito

et al. 2013

J. Chil. Chem. Soc.

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The catalytic activities of palladium complexes containing phosphorus-nitrogen ligands is reported. The catalysts studied showed high activities in the aminocarbonylation of aryl iodides. The palladium complexes reported activities between 100% and 58% in the aminocarbonylation reaction. The reactions are very selective for the double carbonylative amination of aryl halides. The major product is N,N-diethyl-α-oxo benzeneacetamide (96/4). The reaction was made under mild conditions of temperature and carbon monoxide pressure.

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Synthesis of steroid–ferrocene conjugates of steroidal 17-carboxamides via a palladium-catalyzed aminocarbonylation – Copper-catalyzed azide–alkyne cycloaddition reaction sequence

Cited by 21 publications

References 41 publications

Antinociceptive Effects of Lipid Raft Disruptors, a Novel Carboxamido-Steroid and Methyl β-Cyclodextrin, in Mice by Inhibiting Transient Receptor Potential Vanilloid 1 and Ankyrin 1 Channel Activation

Antinociceptive Effects of Lipid Raft Disruptors, a Novel Carboxamido-Steroid and Methyl β-Cyclodextrin, in Mice by Inhibiting Transient Receptor Potential Vanilloid 1 and Ankyrin 1 Channel Activation

Carboxamido steroids inhibit the opening properties of transient receptor potential ion channels by lipid raft modulation

Aminocarbonylation Reaction Using Palladium Complexes Containing Phosphorus-Nitrogen Ligands as Catalysts

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