Inhibition of 6-hydroxydopamine-induced oxidative damage by 4,5-dihydro-3H-2-benzazepine N-oxides

A number of new analogs of 3,3-dimethyl-4,5-dihydro-3H-2-benzazepine 2-oxide, structurally related to the nitrone spin trap α-phenyl-N-tert-butylnitrone (PBN), were synthesized and evaluated for their activity in vitro as protectants against oxidative stress induced in rat brain mitochondria by 6-hydroxydopamine (6-OHDA), a neurotoxin producing experimental model of Parkinson's disease (PD). As assessed by a fluorimetric assay, all 2-benzazepine-based nitrones were shown to decrease hydroxyl radicals (radical dotOH) generated during 6-OHDA autoxidation. The inhibition effects on the radical dotOH formation shown by the 5-gem-dimethyl derivatives, 2–4 times higher than those of the corresponding 5-methyl derivatives, were attributed to the flattening effect of the 5-gem-dimethyl group on the azepine ring, which should enhance nitrone reactivity and/or increase stability of the radical adducts. In contrast, owing to steric hindrance, a methyl group to C-1 diminishes the radical dotOH-scavenging activity of the nitrone group. All the assayed compounds were more potent than PBN as inhibitors of 6-OHDA-induced lipid peroxidation (LPO) and protein carbonylation (PCO), taken as an indicator of mitochondrial protein oxidative damage. The most promising antioxidant (compound 11), bearing 5-gem-dimethyl and spiro C-3 cyclohexyl groups, highlighted in this study as the best features, inhibited LPO and PCO with IC50 values of 20 and 48 μM, respectively, showing a potency improvement over PBN of two order magnitude. Both LPO and PCO inhibition potency data were found primarily related to the radical dotOH-scavenging activities, whereas lipophilicity plays a role in improving the LPO (but not PCO) inhibition, as a statistically valuable two-parameter equation proved.The Spanish authors thank the Ministerio de Educación y Ciencia and the Europe Regional Development Fund (Madrid, Spain, Grants BFI2003-00493 and SAF2007-66114) for financial support. The Italian authors thank the Italian Ministry for Education Universities and Research (MIUR, Rome, Italy; PRIN 2004, Grant No. 2004037521_006) for financial support.S

8H-Chromeno[2′,3′:4,5]imidazo[2,1-a]isoquinoline

The title compound, C18H12N2O, comprises two aromatic fragments, viz., imidazo[2,1-a]isoquinoline and benzene, linked by oxygen and methyl­ene bridges. Despite the absence of a common conjugative system within the mol­ecule, it adopts an essentially planar conformation with an r.m.s. deviation of 0. 036 Å. In the crystal, due to this structure, mol­ecules form stacks along the b axis by π⋯π stacking inter­actions, with shortest C⋯C distances in the range 3.340 (4)–3.510 (4) Å. The mol­ecules are bound by inter­molecular C—H⋯O inter­actions within the stacks and C—H⋯π inter­actions between the stacks

Post-Ugi Cyclization for the Construction of Diverse Heterocyclic Compounds: Recent Updates

Multicomponent reactions (MCRs) have proved as a valuable tool for organic and medicinal chemist because of their ability to introduce a large degree of chemical diversity in the product in a single step and with high atom economy. One of the dominant MCRs is the Ugi reaction, which involves the condensation of an aldehyde (or ketone), an amine, an isonitrile, and a carboxylic acid to afford an α-acylamino carboxamide adduct. The desired Ugi-adducts may be constructed by careful selection of the building blocks, opening the door for desired post-Ugi modifications. In recent times, the post-Ugi transformation has proved an important synthetic protocol to provide a variety of heterocyclic compounds with diverse biological properties. In this review, we have discussed the significant advancements reported in the recent literature with the emphasis to highlight the concepts and synthetic applications of the derived products along with critical mechanistic aspects

Three-Component Reaction of 3-Arylidene-3H-Indolium Salts, Isocyanides, and Alcohols

A novel isocyanide-based multicomponent synthesis of alkyl aryl(indol-3-yl)acetimidates has been established. Starting from aryl(indol-3-yl)methylium tetrafluoroborates, aromatic isocyanides and alcohols, the imidates were obtained in moderate to very good yields. Consecutive four-component synthesis of the above mentioned imidates from N-alkylindoles, aromatic aldehydes, aromatic isocyanides and alcohols was also proposed. In addition, it was shown that in the presence of water, aryl(indol-3-yl)methylium tetrafluoroborates reacted with isocyanides to furnish aryl(indol-3-yl)acetamides

1-Methyl-3-(2-oxo-2H-chromen-3-yl)-1H-imidazol-3-ium picrate

The title salt, C13H11N2O2+·C6H2N3O7−, is the unexpected product of a domino reaction of 3-cyanomethyl-1-methylimidazolium chloride with salicylic aldehyde in the presence of picric acid. In the cation, the 1H-imidazole ring is twisted by 63.2 (1)° from the 2H-chromen plane. In the crystal, cations and anions are alternately stacked along the a axis through π–π stacking interactions between the almost parallel aromatic rings [centroid–centroid distances = 3.458 (2) and 3.678 (2) Å]. The stacks are further linked by C—H...O hydrogen bonds into a two-tier layer parallel to (001)

Recent advances in spirocyclization of indole derivatives

Spiroindolines and spiroindoles are an important class of spirocyclic compounds present in a wide range of pharmaceuticals and biologically important natural alkaloids. Various spiroindolines and spiroindoles possess versatile reactivity which enables them to act as precursors for other privileged heterocycles. In view of the importance of this scaffold, many researchers focused their efforts to develop facile and mild synthetic methods for spirocyclization of indoles. However, the synthesis of spiroindolines and spiroindoles is known to be difficult due to rapid 1,2-migration to restore aromaticity. This review aims to briefly discuss the latest developments to access highly functionalized spiroindolines and spiroindoles to stimulate further research in the field to find new and efficient methodologies for accessing new spiroindolines and spiroindoles.status: publishe

Visible light-mediated chemistry of indoles and related heterocycles

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing the high value of distinctly different ways of bond creation. Indoles and related heterocycles are widely-present in natural products, biologically active compounds, drugs, and agrochemicals. This review summarises the impact of visible light-promoted chemistry on the functionalization of indoles and on the synthesis and modification of indolines, indolin-2-ones, indolin-3-ones, and isatins. Almost 100 references starting from 2012 are cited.status: publishe

Post-Ugi Cyclization for the Construction of Diverse Heterocyclic Compounds: Recent Updates

Multicomponent reactions (MCRs) have proved as a valuable tool for organic and medicinal chemist because of their ability to introduce a large degree of chemical diversity in the product in a single step and with high atom economy. One of the dominant MCRs is the Ugi reaction, which involves the condensation of an aldehyde (or ketone), an amine, an isonitrile, and a carboxylic acid to afford an α-acylamino carboxamide adduct. The desired Ugi-adducts may be constructed by careful selection of the building blocks, opening the door for desired post-Ugi modifications. In recent times, the post-Ugi transformation has proved an important synthetic protocol to provide a variety of heterocyclic compounds with diverse biological properties. In this review, we have discussed the significant advancements reported in the recent literature with the emphasis to highlight the concepts and synthetic applications of the derived products along with critical mechanistic aspects.status: publishe

1-Benzyl-2-(thien-2-yl)-4,5-dihydro-1H-imidazole

Imidazolines are a valuable class of organic compounds, namely ligands of imidazoline receptors, chiral ligands for metal catalysis, synthetic intermediates. The title compound has been prepared through a modified procedure, employing N-benzylethylenediamine and thiophene-2-carbaldehyde under the action of N-bromosuccinimide (NBS) in dichloromethane (DCM) in a good 78% yield