Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• modern drug design [1][2]. They are known to promote higher success rates, when targeting three-dimensional protein molecules [3][4]. Furthermore, a wide variety of spirocyclic fragments can be spotted in natural products [5]. The aspects mentioned unveil the development of synthetic methodologies

• products. For example, spirocyclic Δα,β-butenolides (furan-2(5H)-ones) represent a valuable class of molecular frameworks for drug design and are abundant in nature [15]. Bioactive naturally occurring spiro Δα,β-butenolides include spirofragilide (with anti-inflammatory, antibiotic, antitumor, anti-HIV

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• reactions and indicate their potential offering an efficient approach to fluoroalkylated heterocycles in drug design. Trifluoromethylated acylhydrazonoes Acylhydrazones are a well-established class of organic compounds with the –CONH–N=CH– structure, and some variants show potential pesticidal and

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

• Ksenia Malkova Andrey Bubyrev Stanislav Kalinin Dmitry Dar'in Saint Petersburg State University, Saint Petersburg 199034, Russian Federation 10.3762/bjoc.19.60 Abstract Quinoline-based sulfonyl derivatives, and especially sulfonamides, are relevant and promising structures for drug design. We

• novel quinoline construction and functionalization techniques resulting in new or rare derivatives [17][18][19][20][21][22][23][24][25][26] is an important mission in the field of drug discovery and medicinal chemistry. The sulfonamide group is a known privileged motif in drug design often serving as a

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• of fluorine or a fluorinated functional group into organic compounds has become increasingly prevalent in drug design and development, as fluorine substitution can greatly influence drug potency, pharmacokinetic and pharmacodynamic properties [19]. Therefore, in this study we undertook additional LSF

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• arylidene succinimides; intramolecular oxa-Michael addition; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocycles undoubtedly occupy a special place in drug design [1] and, in general, spirocyclic compounds intended for the interrogation of biological targets have been associated with

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• Jiayue Fu Bingbing Li Zefang Zhou Maosheng Cheng Lu Yang Yongxiang Liu Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, P. R. China Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• , amongst many other uses, provided the background for fragment-based drug design [2][3]. – An ever-increasing computer processing speed leading to an ever-growing list of software-based approaches to try to help in various aspects of drugs discovery. The neural network-based software AlphaFold [4], which

• model of infection. Of note is that the hit to lead process was undertaken by the Centre for Drug Design and Discovery and it resulted in a portfolio of patents assigned to Janssen and the catholic university of Leuven [201][202][203]. Interestingly, these patents are protecting a truly original class

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• associated biological activities and relevance to the naturally occurring alkaloids [1], 1,4-dihydro-3(2H)-isoquinolones (1,4-DHIQs) undoubtedly represent a privileged scaffold [2] for drug design considering such diversely bioactive compounds documented in the literature as ligand for serotonin 5-HT1A

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• Engineering and Biotechnology, University of Applied Sciences, Stephanstr. 7, 64295 Darmstadt, Germany Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Sauletekio 7, 10257 Vilnius, Lithuania 10.3762/bjoc.18.84 Abstract Histone deacetylases

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• the development of multidrug resistant bacteria due to excessive use of antibiotics [2][4]. Heterocyclic compounds are the key components for drug design and synthesis. Among them, 1,3,4-oxadiazole derivatives are attractive and have been investigated for decades. This is due to their promising

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• -butanesulfinyl ketimine; homocoupling; Introduction As bioisosteres of carboxylic acid derivatives, boronic acids have recently emerged as a novel chemotype in drug design, with a number of boron-containing compounds recently being approved by the FDA [1][2][3][4]. In particular, α- and β-aminoboronic acids are

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• purification reduce the efforts in the synthesis of complex molecular architectures. Therefore, cascade reactions are essential in synthetic organic chemistry, even with moderate yields [26]. Recently, such reactions have claimed their much deserving place in drug design and natural product synthesis [27]. In

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

• -driven research led to a large production of standard every-day drugs with antidiabetic, antiseptic, and even anticancer properties. Recently, biguanides have gained particularly increasing attention in several areas, such as drug design, coordination chemistry, and materials science [1]. In this context

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• of fluorine(s) into organic molecules usually leads to significant changes in the chemical and physicochemical properties of the original compounds [5][6]. Hence, the fluorination and related fluoro-functionalization of drug candidates are powerful strategies in drug design to appropriately bias

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• fragments of influenza neuraminidase inhibitors [1], nonsteroidal progesterone receptor regulators [2][3], anti-inflammatory [4], antihypertensive and spasmolytic [5][6][7] agents (Figure 1). It is due to their prospects in drug design that a search for effective synthetic protocols to construct partially

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• , the synthesis of C8-phosphonates of 7- and 9-deazapurines via C–H phosphonation has been reported [17]. On the other hand, azolylpurines are an important compound class that combines two recognized structural motifs of drug design – purines and azoles. Derivatives of this class are known for their

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• knowledge of protein–protein interactions, common characterisation methods to characterise them, and their role in protein complex formation with some examples. A deep understanding of protein–protein interactions and their molecular interactions is important for a number of applications, including drug

• design. Protein–protein interactions and their discovery are thus an interesting avenue for understanding how protein complexes, which make up the majority of proteins, work. Keywords: characterisation methods; heterooligomeric complex; homooligomeric complex; molecular interactions; protein–protein

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• ][4]. Among various nitrogen-containing heterocyclic compounds, pyridine and quinolines are readily found in bioactive compounds [5]. The functionalization of alkylpyridines and quinolines is significant and plays a remarkable role in the efficient drug design [6][7][8]. Due to their conformational

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• applications in materials [21][22][23], life sciences [19][20][24][25][26][27][28][29], and drug design [30][31][32][33]. Consequently, the merging of fluorinated moieties, such as CF3 with selenium could constitute an interesting motif in the design of new molecules, in particular in medicinal chemistry or

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• under observation, could be readily applied to other binding problems as part of a general strategy in drug design or mechanistic analysis. Keywords: binding; conformation; Galaxy; glycoprotein; in silico; Introduction A typical sequence of events in research and discovery is noticing a critical

• view of the features in the system under observation, could be readily applied to other binding problems as part of a general strategy in drug design or mechanistic analysis. A representation of mucin glycopeptide bound to AR20.5 antibody. Chain A is represented as a molecular surface colored by

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• to the insecticidal, myorelaxation, and antiproliferative properties (Figure 1) [1][2][3][4][5][6][7][8][9][10][11][12]. Thus, enormous attention has been paid to 2- or 3-fluoroalkylated indenol derivatives in the field of medicinal and agrochemical drug design since a fluorine atom can very often

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• should be stressed that the exploration of methods for the enantioselective fluorination continues to be an important topic considering the ever-growing role of fluorine derivatives in drug design and development [82][83]. An alternative strategy to prepare related quaternary carbon-containing adducts

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• this review will definitely pave the way for future applications in the fluoro-PKR, and put this emerging reaction at the forefront of drug design. Schematic representation of the Pauson–Khand reaction. Substrates included in this review. Commonly accepted mechanism for the Pauson–Khand reaction

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• in ML and AI by several decades, as shown by the subject of the 2000 Beilstein Bozen Symposium [61]. A recent discussion of AI and ML in chemistry and drug design [62] traces the beginning back to the classical 1964 papers of Hansch and Fujita [63] and Free and Wilson [64]. All that has really

• more stringent than those of a folk ontology [11], which in many ways resembles Halloun’s personal paradigms [76]. Chemistry is not a solved science, so that the above process must be dynamic. Until 2007, for instance, just about all force fields and computer-aided drug design techniques treated the

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