Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• analogues on the mobilization of Ca2+ ions. To date, such structure-activity relationship has only been poorly investigated [38][39][40][41]. We anticipate here that compounds 3 and 4 induce the same effect on Ca2+ mobilization in NGF-differentiated PC12 cells. In particular, both compounds produced a

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• 4 – density functional theory (DFT) calculations at UB3LYP/6-31+G(d,p) level, applied to explain the structure–activity relationship. Dimers showed 2–2.5-fold higher values of kA than their monomers. Model 2 gives information about the effects of the side chains and revealed much higher antioxidant

• – ORAC, which measures the scavenging activity against peroxyl radicals generated by an azoinitiator; and model 4 – a theoretical method used for predicting the activity of the studied compounds to scavenge free radicals by H-atom abstraction and to explain the structure–activity relationship of the

• results only in aprotic media. Comparative analysis of the results obtained by using different models and structure–activity relationship The initiated oxidation of a model hydrocarbon substrate (model 1) has an advantage that in this system the rate of initiation (RIN) is well controlled (constant value

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• structure–activity relationship study with several isomeric oxadiazoles. The regioisomeric substitution around the 1,2,4-oxadiazoles (F [22][23] vs G [23][24]) plays a role in the inhibition observed with the glucosyl group at the 5-position of the 1,2,4-oxadiazole ring being preferred. Isomeric 1,3,4

• . The structure–activity relationship of 5-aryl-1,2,4-oxadiazoles F and G towards GP inhibition highlighted a set of interactions of the aryl moieties with the enzyme’s β-channel [22][23][24]. The amino acids present in this empty pocket are of mixed character and can accommodate hydrophobic groups such

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• described. Keywords: angiogenesis; natural phenolic compounds; structure–activity relationship; synthesis; Introduction The term angiogenesis is commonly used to describe the biological process of blood vessel growth. Nevertheless, it should be more precisely defined as the formation of new blood vessels

• show in vitro anti-angiogenic activity with respect to Pazopanib in both HUVEC tube formation assay and the rat thoracic aorta ring test. They inhibited protein kinase B/Akt and ABL tyrosine kinase in the micromolar range. The preliminary structure–activity relationship is summarized in Figure 5. The

• , this compound showed only weak activity during the proliferation assay (IC50 = 53.8 ± 0.3 µM) and did not inhibit tube formation. A basic structure–activity relationship of the aliphatic mono- and bicyclic acylphloroglucinol derivatives with short acyl side chains indicates that the in vitro

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• backbone modifications for bioactive oligonucleotide analogues. These considerations have led to our recently reported design of a novel artificial internucleotide linkage named 'NAA-modification' (Figure 1) [38]. Ongoing synthetic and structure-activity relationship (SAR) studies on naturally occurring

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• provided close to 20 hormaomycin analogues that have contributed to an understanding of the biosynthetic pathways, the conformational behavior in solution and the structure–activity relationship. After the initial observation that hormaomycin (1) has a marked influence on the secondary metabolite

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• presence of HP-β-CD. Based on quantitative structure activity relationship analyses, this effect can be described by physicochemical parameters such as hydrophobicity or complex stability constants. Indeed, upon complexation, the water-solubility of the preservatives is increased and the concentration of

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than

• , suggesting that TDA may interact with several targets [13]. Here we report on the synthesis and bioactivity of several TDA analogues for investigating the structure–activity relationship (SAR) of this unique marine antibiotic. Results and Discussion Synthesis of analogues of tropodithietic acid For a

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• ) represent an excellent tool for the generation of libraries of small-molecule compounds, for instance they are indispensable for the structure–activity relationship (SAR) studies. Many excellent comprehensive reviews on MCRs have been published. The reviews have covered the significant topics in this field

• interesting compounds. An intensification of studies on the structure–activity relationship of these compounds would provide valuable data on their potential applications. We hope that continued efforts in this field will result in novel nucleoside drug candidates. Selected chemical modifications of natural

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• model catalytic system with predictable, tuneable and easily adjustable properties. Structure–activity relationship studies allowed for identifying the key topological and stereochemical features of the ligands, responsible for achieving high enantioselectivity and for suppressing product isomerization

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• conditions [127]. Amino acids such as Bpa (L-4-benzoylphenylalanine) and Bip (L-4,4'-biphenylalanine) (Figure 5) were attached to the resin-bound peptides by manual coupling steps. Moreover, these first studies led to remarkably truncated NPY analogs [128]. Those structure–activity relationship (SAR) studies

• coupling reagents for SPPS. Spectrum of methods for solid phase-synthesized peptides. AA: amino acid, SAR: structure–activity relationship. Compounds that can be introduced into pNPY (porcine neuropeptide Y) or hPP (human pancreatic polypeptide). NHS: N-hydroxysuccinimidyl, Pam: palmitoyl residue

• –activity relationship studies and backbone modification of biologically active peptide hormones. Nevertheless, there are still some issues that have to be addressed. For instance, incorporation of N-methylated amino acids in order to improve their proteolytic stability often is difficult because of steric

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• opening up an excellent approach for the synthesis of bioactive natural products and derivatives thereof for structure activity relationship (SAR) studies. Keywords: chiral pool; cross metathesis; esterification; β-hydroxy-α-amino acids; natural products; Introduction Besides the proteinogenic β-hydroxy

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• past two decades. In part, this development is due to their often limited accessibility as well as their structural complexity. This situation hampers their use as lead structures for which access to small compound libraries is essential in order to perform structure–activity relationship studies

• pharmacophore of the maytansinoids. All other derivatives show strong to moderate antiproliferative activity, irrespective whether the lack of the N-methyl group, and or the oxirane groups or not. This is in line with the view obtained from structure–activity relationship studies that these tailoring

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• possible. Structure–activity relationship (SAR) studies on synthetic myxocoumarin derivatives as well as in-depth investigation of their antibacterial potential are currently performed in our laboratory and will be reported in due course. Experimental Cultivation and extraction. The preculture of S

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• binding mechanisms as well as structure–activity relationship studies of multivalent glycomaterials is required. Multivalent sugar presentation has been realized on a variety of different scaffolds such as polymers [8][9], dendrimers [10] or naturally-occurring scaffolds such as peptides [11][12][13] or

• important platform for structure–activity relationship studies [15][16][17]. Precision macromolecules combine the advantages of synthetic scaffolds such as polymers with the advantages of naturally-occurring scaffolds such as peptides as they are highly defined, versatile in their structure (linear or

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• alkaloids; structure–activity relationship; Introduction Hedgehog signaling is involved in embryonic development and plays an important role in the maintenance of stem cells, tissue repair and regeneration in adult organisms [1][2][3][4]. The erroneous activation of hedgehog signaling is tightly associated

• conditions are summarized in Table 1. Conclusion In conclusion, we succeeded in identifying the new cyclopamine derivative bis-exo-cyclopamine 6 which surpasses the biological potency of the parent compound by the 25-fold and is stable at pH 1. Further insights were gained into the structure–activity

• relationship of F-ring-modified analogs of cyclopamine and the necessity of the C-21 methyl group for bioactivity and acid stability was revealed. Our designed analogs of cyclopamine are accessible in noticeably shorter and higher yielding synthetic routes than the parent compound, a fact that will further

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• were published [2][5][6][7][8] as well as numerous reports dedicated to derivatives and stereoisomers [9][10][11][12][13][14][15][16][17][18][19][20]. Examination of structure–activity relationship (SAR) revealed a loss of antibiotic activity upon shifting of the methyl group to different positions

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• tested compounds at a dose of 50 mg per kilogram body weight at successive intervals is displayed in Figure 1. According to the results of the biological assay in Table 1, we could deduce the structure–activity relationship (SAR) as follows: (1) among the tested compounds, β-enaminobisphosphonate 15 has

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• , have been widely reported as Aβ-imaging tracers (Scheme 2A). Structure–activity-relationship (SAR) studies on fluorinated chalcones 18a–l have shown that, in general, chalcones with tertiary amines in their structures demonstrate good affinity for Aβ plaques in in vitro models (Ki = 20–50 nM) (Table 1

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• and/or low-abundance targets requires photolabeling [11]. This permits extensive isolation and purification without premature dissociation from the target. Based on the structure–activity relationship (SAR) of 2, we hypothesized that we could integrate photoactivatable functional groups without loss

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• induced by these lead compounds was found to be functional and exhibit appropriate cellular localization [6]. Using these identified lead compounds, Xing et al. [16] performed chemical optimization to develop additional analogues for potential use as therapeutic agents. Structure–activity relationship

• (Figure 12). In a screen of a chemically diverse compound library, Pieper et al. identified an aminopropyl carbazole, P7C3, which was found to increase adult hippocampal neurogenesis in an in vivo assay [53]. Further optimization of this compound through structure–activity relationship (SAR) analysis led

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• inhibit Hsp90 and their structure–activity relationship, less is understood about Hsp90 tumor biology. As a result we and others have been actively engaged in the synthesis of chemical tools designed to probe the function of Hsp90 in transformed systems [9][10][11]. One class of Hsp90 inhibitors of

New GABA amides activating GABA_A-receptors

• Peter Raster,
• Andreas Späth,
• Svetlana Bultakova,
• Pau Gorostiza,
• Burkhard König and
• Piotr Bregestovski

Beilstein J. Org. Chem. 2013, 9, 406–410, doi:10.3762/bjoc.9.42

• GABAA-receptor channels in whole-cell patch-clamp recordings. New GABA-amides, however, gave moderate activation responses with a clear structure–activity relationship suggesting some of these compounds as promising molecular tools for the functional analysis of GABAA-receptors. Keywords: CHO-cells

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• number of myxoviruses [8][12][14]. Structure–activity relationship (SAR) studies suggested both the 2-chloro-4-methylanilide and the central α-thiopropionamide to be moieties that confer good activity. Relatively unexplored in our previous work was the importance of the p-methoxyphenyl ring as well as

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• , we [20] and others [21] reported an in-depth structure–activity relationship of this natural product against its HDAC targets. Dissection of its activity against a panel of HDACs allowed us to highlight structural features responsible for its high inhibitory potency and selectivity. In particular, we