(Phenylpiperazinyl-butyl)oxindoles as Selective 5-HT<sub>7</sub> Receptor Antagonists

Volk, Balázs; Barkóczy, Jozsef; Hegedus, Endre Roland; Udvari, Szabolcs; Szikora, István; Mezei, Tibor; Pallagi, Katalin; Kompagne, Hajnalka; Lévay, György; Egyed, András; Hársing, László G.; Spedding, Michael; Simig, Gyula

doi:10.1021/jm070279v

Cited by 94 publications

(89 citation statements)

References 53 publications

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“…Volk et al reported the alkylation of oxindoles in the 3-position with primary alcohols using Raney W Nickel [20][21][22]. According to Shilov et al, this type of reaction can be referred as an indirect C-H activation [6], while others characterized this catalytic reaction as "borrowing hydrogen" methodology [23].…”

Section: Resultsmentioning

confidence: 99%

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Sipőcz¹,

Lengyel²,

Sipos³

et al. 2016

J Flow Chem

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A novel method for C-H functionalization of heteroaromatic rings by using continuous-flow reactors is reported. Direct alkylation reactions were investigated under heterogeneous catalytic conditions using simple transition metal catalysts at elevated temperature and pressure. As a model reaction, the alkylation of indole was attempted using cheap Raney W Nickel catalyst. Alcohols served both as alkylating agent and as reaction media. The targeted 3-alkyl-indoles were obtained in moderate to good yield with reasonable selectivity. Transient protection on the N-atom increased the selectivity up to 80%. The scope and limitations were also investigated. In summary, direct alkylation with alcohols represents a rapid (residence time of <1 min) and traceless process with high atom economy (88-92%, in those cases where transient protection was not applied).

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Section: Resultsmentioning

confidence: 99%

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Sipőcz¹,

Lengyel²,

Sipos³

et al. 2016

J Flow Chem

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“…[13] Therefore, we tested our catalytic system on the benzylation of oxindole (9). However, we found that only 15 % of the oxindole was benzylated under the reaction conditions described above, presumably due to the fact that the methylene group of 9 is less reactive than those in 1,3-dicarbonyls 1 and 7.…”

Section: Resultsmentioning

confidence: 99%

Pd/C‐Catalyzed Alkylation of Heterocyclic Nucleophiles with Alcohols through the “Borrowing Hydrogen” Process

Putra

Ohta

2015

Eur J Org Chem

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Although amyloid fibrils are associated with numerous pathologies, their conformational stability remains largely unclear. Herein, we probe the thermal stability of various amyloid fibrils. α‐Synuclein fibrils cold‐denatured to monomers at 0–20 °C and heat‐denatured at 60–110 °C. Meanwhile, the fibrils of β2‐microglobulin, Alzheimer’s Aβ1‐40/Aβ1‐42 peptides, and insulin exhibited only heat denaturation, although they showed a decrease in stability at low temperature. A comparison of structural parameters with positive enthalpy and heat capacity changes which showed opposite signs to protein folding suggested that the burial of charged residues in fibril cores contributed to the cold denaturation of α‐synuclein fibrils. We propose that although cold‐denaturation is common to both native proteins and misfolded fibrillar states, the main‐chain dominated amyloid structures may explain amyloid‐specific cold denaturation arising from the unfavorable burial of charged side‐chains in fibril cores.

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“…Moreover, studies have revealed the critical role of the arylpiperazine substitution pattern in determining the receptor affinity. Volk et al 46 found out that electron-donating substituents (-OCH 3 ) were superior to electron-withdrawing (-Cl, -F) for binding to the 5-HT 1A and 5-HT 7 receptors. Our study confirmed that 2-F and 3-CF 3 substituents at the phenyl ring of arylpiperazine were highly preferential for the 5-HT 1A R over the 5-HT 7 R. The influence of substituents 2-F and 3-CF 3 on 5-HT 7 receptor affinity in the group of tested compounds appears to be equivocal, and a spectrum of activities was observed.…”

Section: Biological Evaluationmentioning

confidence: 99%