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

• into the corresponding cis configuration [1]. The reverse reaction can be initiated with a different wavelength. In a biological context, this photochromism was exploited first by Erlanger and colleagues for enzyme inhibitors in 1968 [2], and ion channels in 1971 [3]. Their ingenious approach was

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• promising activity shown by the compounds containing a thiazolidinedione nucleus cover numerous categories such as antihyperglycaemics [5], aldose reductase inhibitors (ARI) [6][7], anti-inflammatory [8][9], anti-arthritics [10], anticancer [11][12][13] and antimicrobial [14][15][16][17][18], etc., has made

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• biological properties. They have been reported to have anticancer [1], antimicrobial [2][3] and antioxidant [3] activities and to act as inhibitors of hepatitis B virus [4]. The dihydro derivatives of tetrazolo[1,5-a]pyrimidines belong to a bit special kind of dihydropyrimidines due to the strong electron

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• bioactivity, allows the probing of pharmacologically relevant systems with spatiotemporal resolution. A hetero-stilbene lead resulting from the screening of a compound that was originally designed as kinase inhibitor served as a starting point for the design of photoswitchable sirtuin inhibitors. Because the

• inhibitors has already been fruitful in the past [32][33]. Therefore, a focused kinase inhibitor library from GlaxoSmithKline was screened for biological activity on human sirtuin isoforms Sirt1–Sirt3. Aza-stilbene derivative GW435821X (2a, Figure 1), initially published as c-RAF kinase inhibitor, was

• identified as a moderately active Sirt2 inhibitor with low selectivity [34][35]. In this work, the photoresponsiveness of the hetero-stilbene core structure is examined. Furthermore, an intramolecular azologization approach is performed in order to obtain photoswitchable sirtuin inhibitors, which could be

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• , the potent SERCA inhibitors, manual docking of compound 1 into SERCA followed by MD simulation (1–10 ns) was performed. For this simulation, four different complexes of SERCA and SL were chosen: i) compound 1 positioned correspondingly to the orientation of DTB in the SERCA binding cavity (simulation

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• ][15][16][17][18][19]. Among all the developed S(VI)–F species, sulfonyl fluoride (RSO2F) was specifically recognized as unique scaffold for covalent protein inhibitors and biological probes with the affinity-driven activation for forming covalent linkages with the amino acid residues of protein

• binding sites (Figure 1) [20]. The smallest member of this family, methyl sulfonyl fluoride (MSF), is known as a selective and irreversible inhibitor of acetylcholinesterase (AChE) [21][22]. The sulfonyl fluoride inhibitors NSC 127755 was found for specifically modifying tyrosine-31 of DHFR in chicken

• aromatic amines with SO2F2 or the fluorosulfurylimidazolium salt have been achieved for assembly of N-sulfonyl fluorides [1][30], which have served as important active precursors for the development of noncovalent inhibitors (Scheme 1, (1)) [1][30][31]. Amides are the key connections in proteins, amides

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• ,1'R)-7 as shown on Scheme 12 and involved formation of the amino alcohols (R)-42 and (R)-47 employing procedures described in Scheme 14. Both (R)-47 and (R)-48 appeared moderate inhibitors of human sphingosine kinases hSphK1 and hSphK2 at 50 μM concentrations as compared to N,N-dimethylsphingosine

• morpholine first required the reaction with iodotrimethylsilane and furnished diamino alcohol 82 which after N-debenzylation and acylation gave (1R,2R)-81. In a similar way other GCS inhibitors, e.g., ᴅ-threo-P4 (1R,2R)-83a and ᴅ-threo-4'-hydroxy-P4 (1R,2R)-83b (Scheme 20) were obtained and examined as

• agonist of S1P receptors while DS-SG-45 was found inactive. Dihydrosphingosines, e.g., safingol and sphinganine itself or as components of dihydroceramides are of interest as enzyme inhibitors [74][75]. Their common vicinal aminohydroxy fragment was efficiently synthesized from the aziridine ketone (2S,1

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• as enzyme inhibitors [26] or antitumor agents [27]. These species are also used as valuable synthetic intermediates [28] and chemosensors for mercury and silver [29][30]. The general methods for the synthesis of O-thiocarbamates and dithiocarbamates traditionally rely on substitution reactions of the

• ), a new quinazolinone derivative in 40% yield (Scheme 6). Notably, these heterocycles are known for their use as antitumor [101], anticonvulsant [102] or epidermal growth factor receptor tyrosine kinase inhibitory agents [103], JNK inhibitors [104] or 5-HT3 antagonists [105]. Earlier, a one-pot

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• course of an enzymatic reaction. Thus, the progress of the reaction can be signaled by a luminescence increase or decrease with time, which enables a highly sensitive real-time luminescence monitoring of the enzymatic activity [6]. STA has been applied to screening enzyme inhibitors or activators

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• , presumably by inhibition of microtubuli formation in cancer cells [22]. More specifically, a series of 60 1,3-diaryl-1-acylpyrazolines was tested as xanthine oxygenase inhibitors that can be efficacious against articular gout, cancer, and inflammation, with IC50 values of four derivatives in the range of 5.3

• ), 669 (m), 627 (w); anal. calcd for C23H18N2O3 (370.4): C, 74.58; H, 4.90; N, 7.56; found: C, 74.67; H, 5.07; N, 7.79. Selected anticancer active 3,5-diaryl-1-acylpyrazoline (left) and xanthine oxygenase inhibitors (center and right). Selected 1-acyl-5-hydroxypyrazolines with analgesic (left, center

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• . Galactose and fructose also allow tumor growth in the absence of glucose. Boronic acid derivatives have gained interest in the last years in different fields such as the development of enzyme inhibitors, drug delivery polymers, saccharide sensors and as boron carriers for BNCT, e.g., amino acid derivatives

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

• ]pyridine-4-carboxamides being SMYD2 inhibitors (an oncogenic methyltransferase that represses the functional activity of the tumor suppressor proteins p53 and RB); the similar structures can be obtained using the methodology of sequential Doebner- and Ugi-type MCRs. In the present work we combined several

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• , nintedanib is employed against pulmonary fibrosis [32], tenidap [33] is a nonsteroidal anti-inflammatory drug (NSAID), while indolidan [34] and adibendan [35] are potent long-acting cardiotonic agents and SM-130686 is a GHSR agonist [36] (Figure 5). Other kinase inhibitors such as sunitinib [37] and

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• /bjoc.15.102 Abstract Galectins are carbohydrate recognition proteins that bind carbohydrates containing galactose and are involved in cell signaling and cellular interactions, involving them in several diseases. We present the synthesis of (aryltriazolyl)methyl galactopyranoside galectin inhibitors

• using a highly diastereoselective hydroboration of C1-exo-methylene pyranosides giving inhibitors with fourfold or better selectivity for galectin-1 over galectin-3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N and dissociation constants down to 170 µM. Keywords: C-galactoside

• uptake and breakdown, respectively. The association of galectins to cell signaling and adhesion gives them roles in several different pathological processes, such as pulmonary fibrosis [6][10], pathological lymphangiogenesis [11], inflammation [12] and cancer [13], with galectin inhibitors demonstrated

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• antagonists [8], cyclin-dependent kinases GSK-3β, CK1 [9] and nitric oxide synthase activity inhibitors [10][11], as well as antibacterial [2], antifungal [12], antihistamine [13] and antitumor activities [14]. Remarkable immunosuppressive properties are inherent to palau’amine (VI) [15]. Ceratamines XIII are

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• convey specificity for prostate cancer cells. Keywords: calcium ATPase inhibitors; Heck- and Suzuki-coupling reactions; hydroquinones; prostate cancer; tethered amino acid; Introduction Sarco/endoplasmic reticulum calcium ATPase (SERCA) is an integral protein that resides in the membrane of the

• sarcoplasmic reticulum (SR) within muscle cells. It transfers Ca2+ from the cytosol to the lumen of the SR at the expense of ATP hydrolysis. Specific inhibitors of SERCA are of significance to human health because of their well-documented value as research tools and their potential as novel anticancer agents

• [1][2]. The natural product thapsigargin (TG, 1a, Figure 1) is one of the most frequently used SERCA inhibitors because of its high specificity and potency. Both cancerous and healthy cells undergo apoptosis after exposure to low concentrations of TG, making TG a highly potent but nonselective

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• Fisher reaction between pyranoses and fatty alcohols of different lengths [8][9]. Alkyl thioglycosides are known for their properties as co-surfactants [10] and present interesting antimicrobial activities [11], acting as glycosidase inhibitors and being resistant towards glycoside hydrolases [12][13

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• bromine atom on the benzene ring may play the key functional role in the inhibitory activity. This study could thus provide a clue for the further biological study and structure modification of marine brominated laurane sesquiterpenoid derivatives towards new effective PTP1B and/or NF-κB inhibitors

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• ciprofloxacin and moxifloxacin (Scheme 1), and reverse transcriptase inhibitors [2], such as nevirapine. Meanwhile, since 1 contains a three-membered ring with high tension [3][4][5][6] and a nitrogen prone to single-electron oxidation, ring opening readily occurs followed by N-centered radical formation. The

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• early example involves the synthesis of protease inhibitors by double Ugi 4CR using pyridine-2,6-dicarboxylic acid, isocyanides, amines and aldehydes (Scheme 2), and the combinatorial implications of this protocol were analyzed [6]. Ugi and Dömling soon realized the potential of such experiments, which

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

• MDM2–p53 interaction could enable p53 and reverse tumor formation [26][27][28]. Based on our knowledge to antagonize the oncogenic protein–protein interaction p53–MDM2 [23][29][30][31][32][33][34][35][36][37][38][39][40] we designed macrocyclic inhibitors in continuation of our previous work [13][23

• indole-based macrocycles, a subset of them was screened searching for MDM2 inhibitors. Compared to our previous indole-based macrocycles 1 following a different strategy (employing a classical Ugi-4C as the key reaction) [23], this one-pot Ugi macrocyclization leading to macrocycles 2 offers speed (one

• basis of the evaluation of the current derivatives as potent inhibitors [33]. The indole moiety could be used not only to constrain the two other substituents but also as an “anchor” mimicking the Trp23. The bulky tert-butyl group would mimic the Phe19 and the macrocyclic ring would fill the Leu26 sub

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• the solid phase), this technology has been exploited to disrupt protein–protein interactions (PPIs) in cancer cells [94][95][96]. Aileron Therapeutics recently launched a stapled peptide platform aiming at developing molecules like ALRN-6924, a stapled peptide that interacts with p53 inhibitors MDMX

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• mainly used for the synthesis of dipeptidyl peptidase IV (DPP-IV) inhibitors, such as alogliptin, linagliptin and other antidiabetic agents [15][17]. Over the years, numerous synthetic pathways were tested for the preparation of 3-aminopiperidine and its N-protected precursors in an optically active form

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• -reciprocal plot, and including a kind of global analysis in resolving steady state inhibition patterns, which are defined by the effects of inhibitors on the slope and intercept, i.e., kcat and kcat/Km. However, there are serious disadvantages in using a double reciprocal plot due to the unequal weighting of