Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• . Succinimides are present in many biologically significant molecules and are investigated as potential pharmacophores in the research of drug discovery [11][12]. Our group has recently devised N-itaconimides for the assembly of succinimide frameworks [13][14][15][16][17][18]. As an extension of these works

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• -benzisoxazolones; 1,5-electrocyclization; nitrenes; photochemical cyclization; Introduction Substituted 2,1-benzisoxazoles display diverse biological activity [1][2][3][4][5][6] (Figure 1) and are widely used as starting materials for the synthesis of important heterocyclic pharmacophores, such as acridines [7][8

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• -adrenergic receptor agonist [3]; lumefantrine, an antimalarial drug [4]; ifenprodil, an N-methyl-D-aspartate (NMDA) antagonist [5]; and tebuconazole, a commercial fungicide [6]. With the importance of 1,2-oxyamino motifs as privileged pharmacophores, the development of facile and efficient access to this

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• , hydroxyalkyl-1,2,3-triazoles were reported as valuable pharmacophores [36]. The products were isolated in good yields and the H-5 signal of triazole (1H NMR) could be observed as a singlet at δ ≈ 7.5 ppm. Compound 11a was further converted into the corresponding bromo derivative 12 in good yield under the same

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity. Keywords: biosynthesis; 13C NMR shifts; pharmacophores; pyridoacridines; synthesis; Introduction In

• ] that summarize their bioactivity. Herein, a synopsis of the newly published bioactivity of pyridoacridine will be provided as well as pharmacophores associated with the activity and a discussion on the evolution of the bioactivity and the structure modification. Cytotoxicity The biologically tested

• new, reported hypotheses on pyridoacridine biosynthesis. Furthermore, the synthesis of analogues related to some of these alkaloids has also been summarized. Biological data have been summarized in this review and different pharmacophores have been highlighted. Some of these skeletons represent good

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• University Munich and Munich Center for Integrated Protein Science, Lichtenbergstr. 4, 85748 Garching, Germany 10.3762/bjoc.11.127 Abstract Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were

• hCAII. a) hCAII (pdb: 2vva [7]) catalyzes the hydration of carbon dioxide to bicarbonate and a proton (left) as well as the hydrolysis of pNPA to acetate and a colored phenolate (λmax = 400 nm). b) Aryl sulfonamide-containing pharmacophores of hCAII. c) Aryl sulfonamide merged to azobenzenes. Crystal

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• for a practical synthesis of vernakalant. Keywords: APS-DMSO; imides; practical synthesis; radical-mediated; vernakalant; Introduction Cyclic imides are privileged pharmacophores and important building blocks for the synthesis of natural products, drugs, agrochemicals, advanced materials and

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• of the ring. The importance of the presented study is amplified by the fact that benzothiopyran and related systems containing a thiopyran moiety, and especially their carboxylic derivatives, are known as important pharmacophores, with key importance for the biological activity of diverse sulfur

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• . Thus, we have found an effective and simple reaction for the preparation of substituted pyrimidine and pyridine derivatives. The resulting compounds are important pharmacophores or may be used as a starting material for synthesis of other functionalized pyrimidines through nucleophilic substitution. X

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• are among the best methods to prepare C-arylglycosides, C-nucleosides and C-glycosidic oligomers when new artificial pharmacophores are approached [17]. With Suzuki cross-couplings C-glycoside analogues of phloriain with antidiabetic properties [18] or aryl-scaffolded dimers and trimers were

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• 1,2,4-trioxalane 191 was synthesized by reductive amination of adamantane-2-spiro-3’-8’-oxo-1’,2’,4’-trioxaspiro[4.5]-decane 190 (Scheme 52). Ozonide 191 is an example of a combination of two known antiparasitic pharmacophores, viz. a peroxide and an aminoquinoline moiety [296]. Arterolane is a fully

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

• well. The tetrahydroisoquinoline moiety of JDTic adopts a pose almost identical to that of naltrindole; the superimposable atoms are shown in pink in Figure 2B [10]. JDTic is thus a bivalent ligand, containing two linked pharmacophores [12], also known as a linked multiple ligand [13]. Bivalent ligands

• [21]. Rather than linking pharmacophores, another approach to bivalent ligands is to design hybrid structures, or merged multiple ligands [13]. As noted above, the HPP moiety of JDTic interacts with many of the key residues for binding of 1, and shares a very similar substructure, suggesting that the

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• amines). Amines are known to be potent pharmacophores, and medicinal chemists have further leveraged their beneficial properties by using chiral versions to enhance protein binding affinities. Furthermore, chiral amines continue to find expanded roles: in organocatalysis [1][2][3][4], as ligands for

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

• , subsequent studies, as detailed below, have shown that conformationally restricted molecules constrained in different conformations, but capable of projecting the key pharmacophores in the same relative area of space, produce active PLG peptidomimetics. Design of photoaffinity labels to identify the PLG

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• attention in recent years because of their broad biological activities [11][12] and therapeutic applications, ranging from antibiotics [13] to anticancer agents [14]. Moreover, the DKP moiety has been exploited as a peptidomimetic scaffold [15][16][17]. Structural unification of THBC and DKP pharmacophores

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

• well as in increasing solubility [20]. Moreover, triazoles can function as attractive linker units which could connect two pharmacophores to give an innovative bifunctional drug, and thus have become increasingly useful and important in constructing bioactive and functional molecules [21][22][23

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• derivative 62 (Scheme 12), which contains aldehyde, carboxylic acid and hydroxymethyl groups as pharmacophores. The dihedral angles of CHO-CH2-CH2-COOH in the cyclopentane analog are very close to those of the carbon skeleton in sordaricin. The synthesis of 62 started with commercially available (+)-3,9