Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• against HDAC8; thus, emphasizing the advantages of drug design on a theoretical basis. These efforts led to the design of potential analogues that warrant further studies to develop therapeutic agents for neuroblastoma. Future research will be aimed at investigating the HDAC class specificity of these

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• efforts must be devoted to exploring the altered properties of the trifluoromethylselenylated compounds. The encouraging results obtained will definitely pave the way for further applications, and put this emerging fluorinated group at the forefront of drug design. Process for the formation of C(sp3

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• conformational entropy penalty upon binding to a protein target, and the approach of constraining the ligand conformation with a ring is widely used in drug design [2]. Accordingly, with increasing interest for sp3-rich molecules, spirocyclic compounds are being considered valuable as molecular platforms for the

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• Constantinos G. Neochoritis Maryam Kazemi Miraki Eman M. M. Abdelraheem Ewa Surmiak Tryfon Zarganes-Tzitzikas Beata Labuzek Tad A. Holak Alexander Domling Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands Chemistry Department, Tarbiat

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• made in order to address and overcome drug resistance, there is an urgent need to develop new antibacterial drug leads that operate through a novel mechanism of action. On the other hand, the past two decades have observed the emergence of protein–protein interactions as a drug design target. During

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• Christian Schutz Martin Empting Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Department of Drug Design and Optimization (DDOP), Campus E8.1, 66123 Saarbrücken, Germany Department of Pharmacy, Saarland University, Campus E8.1

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• , Baltimore, MD 21250, United States 10.3762/bjoc.14.65 Abstract C-nucleosides have intrigued biologists and medicinal chemists since their discovery in 1950's. In that regard, C-nucleosides and their synthetic analogues have resulted in promising leads in drug design. Concurrently, advances in chemical

• stability, ii) altered hydrogen bonding motifs, and iii) altered molecular recognition properties [25][29][37][58]. Because of these changes, C-nucleosides have been useful in the study of RNA and DNA processing enzymes, as well as drug design efforts and novel supramolecular structures [12][29][59

• inhibition of viral polymerase [74]. Synthesis of C2'-substituted furanolactone In view of sugar scaffolds possessing C2' substitutions and their value to drug design, a report by Peifer et al. on the synthesis of C2'-substituted ribonolactones is notable (Figure 11A) [75]. Their finding appends known

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• Frederik Diness Niels J. Bjerrum Mikael Begtrup Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark Present address: Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark Department

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• antibiotics [41]. Our aim in the present study was to synthesize functionalized pyrimidinone systems through rDA reactions. Many of these products are of high importance in drug design due to their diverse biological properties including antimicrobial, antiviral, antioxidant and antitumor activities. In

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• , isoquinoline is regarded as a “privileged scaffold” in drug design, and a large number of drug candidates containing this partial structure are in clinical development [4]. Consequently, synthetic approaches enabling a free variation of substituents on this heteroaromatic ring system are required. Numerous

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• were not included in the above-mentioned review article. Increasing interest in phosphonium salts is also due to their use in drug design. It was demonstrated in the last decade that lipophilic cations having a triphenylphosphonium residue in the structure can be used as effective carriers of

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• [25][26][27][28][29][30][31][32][33] and drug design [34][35][36][37]. Furthermore, very recently, the Hansch lipophilicity parameter of CF3Se has been determined (πR = 1.29) – a high value lying between that of CF3O and CF3S [38]. Consequently, trifluoromethylselenolated molecules could represent

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• phosphodiesterase 10A [15], protease-activated receptor 1 [16], PIM-1/2 kinase [17], antagonists of the corticotropin releasing factor [18][19], vanilloid-1 receptor [20], and modulators for ligand binding to GABAA receptor [21]. As pyridazines are considered as privileged structures in drug design [22], we decided

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• Determining the accurate chemical structures of synthesized compounds is essential for biomedical studies and computer-assisted drug design. The unequivocal determination of N-adamantylation or N-arylation site(s) in nitrogen-rich heterocycles, characterized by a low density of hydrogen atoms, using NMR

• -azine core with a bridgehead nitrogen atom is found in many natural products [5][6] and biologically active synthetic compounds [7][8]. The purine-like scaffold of these nitrogen-containing heterocycles is frequently used in medicinal chemistry and drug design. For example, 6-nitro-1,2,4-triazolo[5,1-c

• studies and computer-assisted drug design, e.g., molecular docking techniques. Thus, the development of effective methods for the unambiguous determination of N-alkylation site(s) in the azolo-azine series is important. The data that are required to solve this problem could be provided by 15N NMR

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• and trifluoromethyl groups in a single structure generates a new family of compounds with potential application as agrochemicals or in drug design. A variable temperature NMR study allowed the determination of rotational barriers of 14.6, 18.8, and 15.9 kcal/mol for the C–N bond in the dithiocarbamate

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• ][11][12][13][14][15][16][17][18][19][20], which continue to remain in the focus of attention for many research groups worldwide as targets for total synthesis and to serve as inspiration for exercises in drug design. Although many preparative methods of assembly of these structural units have been

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• therefore the variation in the carbonyl functionality may have implications in drug design. Moreover, Asu and its congener 2-aminopimelic acid have been used as ethylenic equivalent of a disulfide linkage [4]. Other applications of Asu in peptide engineering and as a building block are of notable importance

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• hexahydropyrrolo[1,2-b]isoquinolone derivatives fused with benzene 10 that have pronounced three-dimensional features and potentially contain several quaternary carbon centers (Figure 2). The first aspect has been recently recognized [29] as a central principle in drug design ensuring effective interaction of

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• , as these enzymes can be utilized in drug design and hence has value to the medical community as well. These enzymes also are generally regioselective for the position 9 of purines and the position 1 of pyrimidines which is a persisting challenge in the chemical synthesis of biologically active

• absence of a C2–OH group (Table 5, entries 5 and 6). The remarkable stereospecificity of this reaction coupled with its ability to provide C-glycosides, a class of compounds important in natural products [66] and drug design [67], makes this methodology a very powerful one. One very clear drawback

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• obtained in the absence of its epimer, epi-8. Moreover, the chemical entities described herein offer opportunities for studies in glycobiology, biomedicinal chemistry and drug design. The use of these compounds as starting material to access new small ligands as GPCR modulators is ongoing in our

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• - and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research. Keywords: computer-aided drug design; GPCR; metadynamicxs

• its distance from them in the G-protein phylogenetic tree [1]. Later, when the β2-adrenergic receptor structure was published [8] it was concluded that homology models would play an increasingly important role in computer-aided drug design (CADD) [24]. With hindsight, this conclusion was perhaps a

• little optimistic. However, the situation has changed considerably in the last five years. Not only are more (and more relevant) GPCR structures available, but modern protein force fields have attained a level of reliability that makes them truly predictive in most drug-design scenarios; it was found

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• Tue Heesgaard Jepsen Emil Glibstrup Francois Crestey Anders A. Jensen Jesper Langgaard Kristensen Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark 10.3762/bjoc.13.98 Abstract We report an

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• years deuteration became also an efficient tool in drug design [6]. Pyrazolo[1,5-a]pyridine and 1,2,4-triazolo[1,5-a]pyridine scaffolds attracted significant attention to the medicinal chemistry community during the past decade. For example, pyrazolo[1,5-a]pyridine derivatives were used in the design of

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• Yan Chen Xiaoman Wang Junchang Wang You Yang Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China 10.3762/bjoc.13.79 Abstract A [4 + 3] synthesis of D-manno-heptulose is described. The cascade