Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• to the authors whose important contributions may not be included. By concentrating on these pivotal studies, we strive to offer a clear and concise perspective on current research trends and breakthroughs in this field. Keywords: Alzheimer; depression; epilepsy; multicomponent reactions; Parkinson

• improved biological activities. Employing this approach, Kushwaha et al. [34] synthesized a series of compounds containing benzofuran, tetrazole, and pyrazole within a single structure (Scheme 2). Benzofurans and tetrazole pharmacophores have demonstrated potential anti-Alzheimer activity by inhibiting

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• compounds with anticancer, antihypertensive, antiinflammatory, antioxidant, antimicrobial, antifungal, antimalarial, antitubercular, antidiabetic, antifilarial, anti-Alzheimer, antiepileptics and other activities [1][2][3][4][5][6][7][8][9][10][11]. The concept of "privileged structures" in medicinal

• , Leishmania amazonensis, Tcruzi epimastigota, Dengue larvicida, and for selected cases Alzheimer and Sars-COVID. For more details, see Table S1 (Supporting Information File 1). Conclusion In summary, we have demonstrated the catalytic regioselective Biginelli synthesis of new S-heterocyclic systems ‒ 4-aryl

• potential high activity against diseases associated with these species: Alphis gossypii, Tripomastigote Chagas, Candida albicans, Tcruzi amastigota, Leishmania amazonensis, Tcruzi epimastigota, Dengue larvicida, and for selected cases Alzheimer and Sars-COVID. Number of aryl-substituted Biginelli-type

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• activities is displayed by this pharmacologically rich nucleus which includes antibacterial, antifungal, anticancer, anxiolytic, antimalarial, antiviral, anti-HIV, anti-Alzheimer, and anticonvulsant activities etc. [18][19][20][21][22][23][24][25][26]. Potent anticancer activities are shown by the majority

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• scaffolds with versatile medicinal properties, including anti-Alzheimer, anti-inflammatory, anticancer, antidiabetic, and antileishmanial activity [1]. Since the first synthesis of paullones (scaffold A in Figure 1) in 1992 [2], and disclosure of their Cdk inhibiting potential, several other analogues were

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• against cancer [6][7], tuberculosis [8], Gram-positive bacteria [9], and they are used in treatment of epilepsy [10] and Alzheimer disease [11][12][13]. The synthesis of compounds of the 1,2,4-oxadiazole series is an actual task in organic and medicinal chemistry (see selected reviews on this topic [14

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• derivatives as potent anti-Alzheimer agents (171, 172) by a Buchwald coupling of the corresponding C3-substituted amines 170 and indole 5/6-bromides 169 (Scheme 23) [113]. Cyano, 4-piperidinyl and N-methylpiperidinyl substitutions at the indole and 7-azaindoles were necessary to improve the brain penetration

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• against different types of diseases, such as cancer [1][2], malaria [3][4], Chagas disease [5][6], HIV [7][8], depression [9][10], amnesia [11], Alzheimer [12], and maybe even in a more recent scenario, COVID-19 [13]. Even though many compounds are found to present activity against these diseases, only a

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• effective against cervical cancer (HeLa cells) [8]. Moreover, γ-carbolines are known for their well-established DNA intercalating [9] and anti-Alzheimer [10] properties. The classical Graebe–Ullmann synthesis [11] of γ-carbolines, one of the very early protocols in the domain, is based on the thermal

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• [8][9][10][11][12], and inhibit enzyme function [13] in vitro, they also exhibit interesting effects in vivo like the reversal of Alzheimer plaques in mice [14], tumor inhibition [15], and reduction of HIV infectivity [16], all while showing almost no toxic side effects [14][17]. In calixarenes with

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• several neurodegenerative diseases (Alzheimer [8], Huntington [9], Parkinson [10]) as well as to stroke [11] and epilepsy [12]. Two main classes of receptors, each of them containing three subclasses which are further divided into subtypes have been established for glutamic acid. To understand the

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• may be found in crolibulin, an antitumor agent, undergoing phase II clinical trials [31], chromenotacrine CT-6, a potential anti-Alzheimer agent [32], and pranoprofen, a marketed anti-inflammatory drug [33]. Combination of chromene and imidazopyridine rings led to the discovery of compound A with

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• diseases [51][52][53]. A number of studies also suggested a possible implication of TLR4 in cardiovascular disorders [54] and Alzheimer desease – associated pathology [55]. Therapeutic down-regulation of the TLR4 signaling is believed to be beneficial for treatment of numerous chronic and acute

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• intensively discussed [33][34][35]. Moreover, the effect of enzymatic phosphorylation on Alzheimer-relevant APP was demonstrated already decades ago [36] and has been followed up in plenty of studies since then [37][38][39][40]. Phosphorylation experiments were also transferred to model peptide systems by our

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• chemistry over the years [1]. Isoxazoles have been found in natural products [1], and they exhibit anticancer [2], antiviral [1], anti-inflammatory [3], antidiabetic [4], anti-Alzheimer [5] and many other types of biological activity [6]. Isoxazolines and isoxazoles have been applied as chemosensors, liquid

Biradical vs singlet oxygen photogeneration in suprofen–cholesterol systems

• Fabrizio Palumbo,
• Francisco Bosca,
• Isabel M. Morera,
• Inmaculada Andreu and
• Miguel A. Miranda

Beilstein J. Org. Chem. 2016, 12, 1196–1202, doi:10.3762/bjoc.12.115

• from inflammation to cardiovascular and Alzheimer diseases [1][2]. This type of damage can be induced via free radicals or singlet oxygen (1O2) [3][4]. The former generally involves hydrogen abstraction (HA) of an allylic hydrogen and can be achieved by photosensitizing agents in combination with UVA

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• of activation. This method provided a route to access the enantiomerically enriched tetrahydrocarbazole scaffold-containing compounds 14 (Scheme 6 and Scheme 7) [29]. One of these valuable products is a synthetic precursor of the pharmacologically active compound 15, used to treat Alzheimer and other

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• protein (Aβ), characteristic aggregation in Alzheimer disease (AD), and more specifically Aβ42 peptide allowing its conformational change and its stabilization into small, nonfibrillar complexes, less toxic for neuronal cells [20][21][22][23]. The most efficient representative, scyllo-inositol, was shown

• to be able to reduce plaque burden and to improve the performance on memory tasks in animal models of Alzheimer disease [24][25][26][27][28][29]. Scyllo-inositol was recently used in human clinical trials for the treatment of patients suffering from AD [30][31]. McLaurin has also demonstrated that

• the corresponding fluoroinositol (1-fluoro-1-deoxy-scyllo-inositol) was also a good candidate to limit this aggregation. However, in vivo studies in animal models of Alzheimer disease with 1-[18F]fluoro-1-deoxy-scyllo-inositol used as radiotracer for positron emission tomography (PET) have shown that

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• template 16 to obtain threefold boronic ester 17. The miniamyloid 17 assembles from seven components by imine and boronic ester bonds between the peptides and the template. The relative orientation and spacing of the peptides mimic the assembly of peptides in Alzheimer β-amyloids. Keywords: Alzheimer

• ; boronic acid; miniamyloids; NMR spectroscopy; peptides; Introduction Aβ peptides spontaneously form amyloid fibrils which are a major component of Alzheimer plaques [1]. The cooperative thermodynamically-driven process of fibril formation has an induction period which depends on the conditions of amyloid

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• pharmaceutical intermediate [71] and a promising anti-Alzheimer [72], we found that the Pd/Cu-catalyzed Sonogashira coupling reaction of 3-bromoaniline (1a) with 4 is the actual industrial process for the synthesis of 2a in high yield [73][74][75] (Scheme 1). However, when the reaction is performed at industrial