Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• designing a photoswitchable drug is to place the switch at a position in the pharmacophore that allows switching of the biological effect by irradiation with light without greatly reducing the overall activity by unselective interference with the inhibitor–receptor interaction. This is a difficult task

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• as a vital pharmacophore in medicinal chemistry due to its special biological activity [11][12][13]. In particular, the tricyclic benzimidazole skeleton is ubiquitous in many bioactive compounds and therapeutic agents (Figure 1b) [14][15][16]. Recent studies have shown that fluorinated benzimidazole

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• combining the indole moiety with the 1,5-disusbtituted tetrazole pharmacophore could increase the non-covalent interactions, including π–π stacking, hydrogen bonding, and hydrophobic interactions. This combination may improve the pharmacodynamic profile, providing a solid foundation for developing compounds

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• tool used to identify energetically favourable binding sites, known as molecular interaction fields (MIFs), on molecules with known structures. GRID has various applications, including ADME prediction, site of metabolism prediction, ligand-based and structure-based design, pharmacophore elucidation

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• pharmacophore in medicinal chemistry and the challenges in obtaining either N1- or N2-alkylated indazoles as the dominant regioisomer [30][34][35][36][37][38][39], we were interested in exploring the regioselectivity with methyl 5-bromo-1H-indazole-3-carboxylate (6, Figure 1) as a multifunctional model compound

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• course of an extensive screening of NMDA (N-methyl-ᴅ-aspartate) channel blockers resembling 1,2-diphenylethylamines. A channel pharmacophore description was envisaged collecting data from stereoisomers of 1,2-diphenylethylamine derivatives and 1,2-dicyclohexylethylamine derivatives. Among them, isomer (S

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• linker or pharmacophore group. In fact, more than one hundred FDA-approved drugs are sulfonamide-bearing small molecules. Screening libraries of aromatic and heteroaromatic sulfonamides gave rise to the discovery of multiple physiologically active compounds [27][28][29][30] including important

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• -triazole pharmacophore via click chemistry reaction catalyzed by copper. The introduction of a proper 1-(3-nitrophenyl)-1H-1,2,3-triazole substituent into triterpenes resulted in promising anti-RSV activity, compared to that of RBV, one of the few drugs available for treating RSV infections. Compound 8 was

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• , T12 YN60, Ireland 10.3762/bjoc.17.127 Abstract The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• . Furthermore, it usually displays a high polarity and consequently good aqueous solubility. These features render biguanides an attractive chemical function in medicinal chemistry, where it tends to establish as a valuable pharmacophore for drug discovery. Currently, seven biguanide drugs are commercially

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• of socially significant diseases, is fruitful. The design of biologically active compounds based on C60 is determined, on the one hand, by the ability of its shell to serve as a transportation unit for pharmacophore groups, and on the other by the need to identify the capability of the fullerene core

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• cell lines [44]. Here, the incorporation of CF3 and CF3O groups as NMR reporters into the tumour-targeting drug conjugates enabled the direct investigation of the mechanism of the pro-drug metabolic cleavage and the pharmacophore release by real-time 19F NMR analysis. 19F NMR was also employed as a

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• containing practically significant heteroaromatic rings and a biologically active and hydrolysis-resistant phosphonate group, as it has been reported that the combination of several pharmacophore fragments in one molecule can lead to a synergistic increase in biological activity or an additional variety of

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• molecular photoswitch that has only recently been applied as a photoswitchable pharmacophore for control over bioactivity in cellulo. Uniquely, in contrast to other photoswitches that have been applied to biology, the pseudosymmetric hemithioindigo scaffold has allowed the creation of both dark-active and

• colchicine or its analogue combretastatin A-4 and was bioactive, while the other isomer clashed with their SAR and was less active [18]. That approach of directly embedding a photoswitch motif inside the pharmacophore seemed to be more promising for photopharmacology than the synthetically more

• straightforward attachment of photoswitches on the pharmacophore periphery. We expected that embedding (which is referred to as azologization in the case of azobenzene-based photopharmaceuticals [19]) should in general lead to more significant alterations of the binding-relevant structure, and increase the

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• pharmacophore (the drug is “switched OFF”), whereas the other photoform should restore the biological activity of the active element (the drug is “switched ON”). Correspondingly, an inactive drug (the OFF photoform) can be safely administered, and subsequently it can be locally activated for the therapy

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• constructed by adding a photoswitchable unit to a pharmacophore [14][15], thereby significantly increasing the size of the compound and decreasing its potential as a drug. Therefore, we were interested in exploring other substitution patterns for these aminoazobenzene derivatives. To allow for the possibility

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• reported to show potent antiallergic [1][2][3][4], anticancer [5][6], analgesic and anti-inflammatory activity [7] (Figure 1). Similarly, benzofuroindol has been studied intensively as a pharmacophore of calcium-activated potassium channel (BKCa) opening activity [8][9][10][11][12][13]. Hence

• ']diindoles 6 exhibited an even stronger activity than derivatives 5 which might be caused by their bigger heterocyclic moiety. All compounds 5 and 6 were active to inhibit enzymes h-NPP-3, which suggests that the furoindole core structure is the main pharmacophore for the inhibition against h-NPP, while

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• preserving all the favorable photophysical properties of the parent 4FAB scaffold, however, the tetrafluoro motif can significantly perturb pharmacophore–protein interactions. In contrast, we found that the freely diffusible 4FABTA probe could be pre-set with green light into an OFF state that was

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• potential cancer target. Further structure–activity relationship studies are required to fully characterise this potential anticancer pharmacophore. This study again demonstrates how taxonomy-guided exploration of fungi is a highly effective strategy for identifying novel bioactive metabolites. Experimental

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• -isoGln pharmacophore is essential for the immunostimulatory properties but the introduction of lipophilic substituent into MDP analogues can increase its adjuvant activity [12][18]. Up to now, our research was directed towards isomeric desmuramyl peptides containing lipophilic unnatural amino acid

• peptides were prepared and characterized. In their structures, all glycopeptides comprised of mannose and the key pharmacophore – desmuramyl peptide. These moieties are connected through a glycolyl or hydroxyisobutyryl linker and additionally modified on N/C terminus with an adamantane subunit. The

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• available N-unsubstituted 2-hydrazinylpyridines and 2(1)-hydrazinyl(iso)quinolines. Due to the presence of the fused [1,2,4]triazole hetaryl pharmacophore fragment and a phosphoryl group in the obtained compounds they are of great interest as promising substances with potential biological activity

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• virus infections [20], etc. Among the variety of heterocyclic acids used in Ugi-4CR [15][16][17][18][19][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] only a few of them in addition to bearing a simple pharmacophore core (group I, Scheme 1) are also

• example for the combined application of Doebner and Ugi-type MCRs although the former condensation easily affords the azoloazine pharmacophore that is able to participate as an acid component in the latter reaction. It should be noted, that Cowen et al. [6] reported N-substituted-1H-pyrazolo[3,4-b

• 70 °C) and a small focused library of 23 Ugi products was created. The target compounds containing two pharmacophore pyrazolopyridine and peptidomimetic moieties were screened for their antibacterial activity and demonstrated weak antibacterial effect. Molecular structure of N-(2-(tert-butylamino)-1

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• ) [41] or photochromic ligands (PCLs) [31][42]. The latter ones represent small molecules, which can either be engineered via extension of the chemical structure of a known pharmacophore towards a photochromic moiety or via replacement of certain parts of the biomolecule to generate a photochromic

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• of higher complexity by employing simpler, more efficient, catalytic methods that are also environmentally friendly. Molecular hybridization has emerged as an interesting strategy for the synthesis of bioactive molecules with improved properties by combining two or more pharmacophore fragments in a