Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• started our investigation with the preparation of azide-substituted cationic titanocenes. To this end, the titanocene carboxylates 1–3 shown in Figure 1 were employed as substrates because their substitution pattern should allow a first simple assessment of structure–activity relationships. The compounds

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• quantitative structure–activity relationships (QSARs). In most of the studies related to aglycon modifications, it was concluded that aromatic glycosides possessed improved binding properties due to the ubiquitous presence of aromatic amino acids in the cognate binding sites [23][24][25]. This is also

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• physalins were found to be cytotoxic to cancer cells with an aberrant Hh signaling pathway and inhibited the expression of Hh signaling-related proteins. Structure–activity relationships were observed in the Hh inhibitory activity of physalins and the left part of the structure was found to have an

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• for linked, fused or merged bivalent derivatives of 1. Keywords: allotopic; bivalent ligand; designed multiple ligand; JDTic; κ-opioid receptor; natural products; Salvinorin A; Introduction The structure–activity relationships of salvinorin A (1), a potent and selective κ (kappa) opioid, have been

• work, all published mutagenesis-based models placed the furan ring in contact with Tyr3207.43 [1]. This interaction is plausible in light of the structure–activity relationships of opioid antagonists. In JDTic, the N-substituent of the HPP moiety interacts with Tyr3207.43 [7], and N-furanylalkyl

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• sourced material and unsatisfactory overall yield. As part of our study concerning the structure–activity relationships and chemistry of new antibiotics, we sought to develop a reliable and efficient synthetic route starting from inexpensive, commercial sources to provide access to chalcose. We describe a

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• influenzae, including an efflux-negative strain, and 2 strains of Escherichia coli, including an efflux-negative strain (Table 2). Relevant physicochemical properties of the analogues are also shown in Table 3. These were used to elaborate structure–activity relationships (SAR) [26]. In the assay against

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

• . The anti-inflammatory and the antinociceptive properties of the prepared compounds were screened and the structure–activity relationships were studied. The anti-inflammatory properties of many tetrazole [21][22][23] and pyridazine derivatives have also led to their clinical application as NSAIDs (e.g

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• some ring as opposed to chain analogues, allowing for the description of structure–activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212. Keywords: antifungal; Candida albicans; chemosensitizer; fluconazole; Molecular Libraries

• closely related analogues were prepared to enable investigation of possible structure–activity relationships (SAR) [18]. In addition to indazole 1, two other structurally distinct scaffolds (2 and 3) were also selected for follow-up studies and those works are communicated elsewhere [19][20]. Chemistry

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

• efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. This review provides a survey of chemical probes developed to date for AD with emphasis on synthetic methodologies and structure–activity

• relationships with regards to affinity for target and brain kinetics. Several probes discussed herein show particularly promising results and will be of immense value moving forward in the fight against AD. Keywords: Alzheimer’s disease; in vivo detection; near-infrared fluorescence probes; PET/SPECT imaging

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

• –activity relationships (SAR) through analogue synthesis [9]. This probe was discovered after two separate screening campaigns totaling ~110,000 compounds. At concentrations up to 8 μM, 4 failed to suppress PKCβ and PKCθ (the PKC family members implicated in TCR/BCR signaling) and IKKβ, while known PKC and

• other NF-κB activation pathways such as those including the cytosolic proteins CARMA1, Bcl-10, MALT1, TRAF6 and Ubc13 [8]. The first probe identified within this series was the benzimidazole ML029 (4), which exhibited an IC50 of 0.07 μM in the HEK 293 cell assay with corresponding well-defined structure

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• assessment of reactivity: property- or descriptor-based and direct modeling of the PES, especially of the rate-determining TS. The first type is generally termed QSAR (quantitative structure–activity relationships), where experimentally known or calculated properties are fitted to observed reactivities

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

• dopamine receptors. PLG peptidomimetic design Although several studies of structure–activity relationships on PLG had been carried out early on [12][13][14], these studies did not provide information about the conformation PLG adopts to produce its pharmacological actions. NMR spectroscopic studies [15

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

• benzimidazole nitrogen in these crystal structures results in pseudo seven-membered rings. Whether this conformation is biologically relevant is unknown. Structure–activity relationships A small set of compounds was synthesized based on variations of 1 by replacing the p-methoxyphenyl group with other

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• , with competitive Passerini reaction in the latter case [28][29]. With the general process in place, the MCR approach was employed to generate a library of synthetic derivatives of 1 with the hope of gaining a first glimpse of structure–activity relationships (SAR), and to give hints for further

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• features applying also to so-called membrane-transducing peptides [11][12]. Results Preparation of phallotoxin derivatives Attachment sites in phalloidin (Figure 1) for conjugation with uptake-mediating moieties were chosen based on our knowledge of structure–activity relationships in phalloidin [1]: As

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• difficult to determine structure–activity relationships [7][8]. More recently, the solid-phase synthesis of a number of analogues of the fusaricidins has been reported. However, in all cases, the side chain 3-hydroxy group was not incorporated into the structure [9]. By total synthesis of both side-chain

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• secondary alkylamine due to the different conformational changes induced. This promising result prompted us to further investigate the structure–activity relationships (SAR) of Sant-75. Herein we describe our efforts in the development of synthetic methods for the construction of a library of Sant-75

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• ]. Synthetic glycoproteins An important task for chemists is to make homogenous glycoproteins and complex glycopeptides available for biological research. Studies of glycosylation effects on protein conformation, stability and structure–activity relationships (SAR) are a few examples of the applications of

Phytoalexins of the Pyrinae: Biphenyls and dibenzofurans

• Cornelia Chizzali and
• Ludger Beerhues

Beilstein J. Org. Chem. 2012, 8, 613–620, doi:10.3762/bjoc.8.68

• did [12], whereas the opposite tendency was observed for antifungal activity [26]. However, more biphenyls and dibenzofurans need to be tested for their antibacterial and antifungal potentials in order to allow for reliable conclusions concerning structure–activity relationships. The array of

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• -molecule structure–activity relationships for compounds 1–8. Grids are given in the following sequence in each case: Square-top (green); flicker (yellow); multiple-opening (blue); spike (red); erratic (purple). Yellow arrows indicate hydrocarbon homologs; green arrows indicate expansion of aromatic units

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• investigate structure–activity relationships in various biological tests or photonic applications. The ready availability of starting materials, mild reaction conditions, short reaction times, experimental simplicity and satisfactory yields contribute to the usefulness of this method. The possible biological

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• ; although some exhibited weak activity. However, all of these results have made a significant and invaluable contribution to the development of new potent antiviral, cytotoxic or antibacterial agents and have elucidated possible structure–activity relationships. Investigated derivatives. Modifications of

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• which an azide and an alkyne undergo a 1,3-dipolar cycloaddition reaction in the presence of a catalyst such as copper (Scheme 1) or ruthemium (Scheme 2) [27]. Some new synthetic methods for 1,2,3-triazoles are given below (Scheme 3, Scheme 4) [28][29]. Structure activity relationships have revealed

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• can be identified in the clinical antitumor agents etoposide, teniposide [21] and lignan lactone podophyllotoxin [22], and structure–activity relationships have shown that the methylenedioxy moiety is fundamental for cytotoxic activity since it can be metabolized by CYP to form metallo–carbene