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

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

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

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

• active site located on the cytosolic side of the membrane [10][11][12][13][14]. For previously reported SAR studies on muraymycins and their analogues, the fatty acid side chain was either neglegted or replaced with a structurally distinct lipophilic mimic [15][16][17]. Mansour and co-workers found a

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• was still active, because it had been shown in several SAR studies that limited variation of the amine or alcohol component at the C-terminal amide or ester moieties of the dolastatin family members can be tolerated without much loss of cytotoxicity. This includes epimerization of the thiazole

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

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

• towards Aβ aggregates with Ki values ranging between 5.3 nM for 29a and 19.3 nM for 29c (Scheme 3A) [16]. SAR studies suggest that, as with chalcones, the tertiary amine in these flavones was important for binding and tracing Aβ aggregates in mouse models, as they consistently outperformed secondary and

• all cases. However, pharmacokinetics for these agents were less than ideal as both showed long retention in the brains of normal mice, which is indicative of nonspecific binding. A series of iodinated benzothiazoles 59a–o was synthesized using methods similar to those described above and SAR studies

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

• 29 (Figure 4), i.e., an analogue of 2 with slightly greater potency (IC50 = 6.4 µM) that was identified in later SAR studies [23]. UV irradiation was applied for 30 min at room temperature by using the long-wavelength setting of a hand-held illuminator (366 nm, UVL-56 lamp, UltraViolet Products, San

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• transduction in reporter cell lines containing either low or overexpressed NOD2 proteins. Probes 13 and 17 were also selective over the non-NOD-stimulated NF-κB pathways (TNF-α, doxorubicin and PMA/ionomycin) in these reporter assays. Both of the probes, and their close analogues as discovered through SAR

• studies, selectively inhibited IL-8 secretion and the biologically relevant terminal effect of NOD1 (γ-tri-DAP) dependent NF-κB activation. Additionally, they neither inhibited NOD2-dependent nor TNF-α-dependent IL-8 secretion in biologically relevant MCF-7 cells. While 13 is the more potent and selective

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

• (SAR) studies revealed that the thioether and pyridazine moieties were essential molecular components for increasing EAAT2 protein levels [16]. Of the analogues developed, several thiopyridazine derivatives (Figure 4) were found to increase EAAT2 levels greater than six-fold over endogenous levels in

• analogue was tested in SOD1 G93A transgenic mice that were treated daily by i.p. administration with 30 mg/kg of CHD derivative compound 15 starting at 6 weeks (prior to symptom presentation). A 13% increase in lifespan was observed in treated animals as compared to controls [34]. SAR studies with PYT

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• mimicking type VI β-turn and polyproline II helix conformations Early SAR studies on PLG showed that when the glycinamide residue was substituted with both L-and D-prolinamide residues, active dopamine receptor modulating peptides 43 and 44 (Figure 6) were obtained [13]. Likewise, triproline analogues of

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

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• -amino acid, usually β2-homoalanine. Finally, unit D is leucic acid, the hydroxy analogue of leucine. Numerous synthetic analogues have been obtained in the frame of structure–activity-relationship studies (SAR-studies), as reviewed in [17][18]. Unit A para-alkoxymethyl derivatives of cryptophycin-52

• tumor cell line KB-3-1 [21] (Figure 2). The chlorohydrin derived from 4 that also contained a fluorine substituent in the para-position of the unit A phenyl ring was patented as a promising candidate [22]. In the frame of our on-going SAR studies on cryptophycins [19][23][24][25][26][27][28][29][30], we

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR) studies were also

• groups comprising aminoacetal, β-ketoimide and indole groups [31][32][33][34]. Evaluation of in vitro antitrypanosomal activities of the synthetic collections and preliminary SAR studies are also described [35][36][37][38][39][40][41]. Results and Discussion First, we assembled a linear precursor 24 with

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• company [3]. From structure–activity relationship (SAR) studies it was found that the addition of substituents at the 3- and 4-position of the pyrrole scaffold significantly increases potency when compared to the more classical 2,5-disubstituted pyrroles. This study culminated in the discovery of

• of glucagon release. Consequently, insulin secretion increases leading to decreased blood glucose levels in diabetes type II patients. Structurally, this novel antihyperglycaemic consists of a fluorinated β-amino acid which is coupled to a trifluoromethylated triazolopiperazine (Scheme 55). In SAR

• studies this fused heterocycle was found to be more metabolically stable compared to earlier leads that contained a simple piperazine ring. Furthermore, the triazolopiperazine is not only involved in a tight H-bond network within the active site of DPP-IV, but also in π-stacking with the aromatic ring of

A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

• Benedikt Sammet,
• Mathilde Brax and
• Norbert Sewald

Beilstein J. Org. Chem. 2011, 7, 243–245, doi:10.3762/bjoc.7.32

• interacting with the β-subunit of α/β-tubulin heterodimers. Numerous natural and artificial analogs have been analysed in structure–activity relationship (SAR) studies. The unit B of cryptophycins contains a considerably modified D-tyrosine derivative (Figure 1). Substituent variations at unit B are not well

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• important targets in the treatment of diabetes and dyslipidemia. Azetidinone acid derivatives 110 were discovered to be new subtype-selective PPARα/γ agonists. For detailed structure–activity relationship (SAR) studies, diversity was introduced very efficiently by a copper-mediated N-arylation of

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• comparison to Alogliptin in vitro. Nevertheless, to gain further insight we plan to conduct Structure-Activity-Relationship (SAR) studies for this class of compound that would eventually help to identify a potential lead possessing favorable pharmacological properties. Conclusion In conclusion, we have