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Search for "inhibitor" in Full Text gives 405 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.

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

Graphical Abstract
  • activities of this supramolecular complex (Scheme 5), with positive in vitro activities in 20S proteasome core particles isolated from rabbit erythrocytes [28]. The sulfonamide 30 (Scheme 6) has been evaluated as inhibitor of human carbonic anhydrase I/II (hCA I and II), which catalyze the reversible
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Published 02 Aug 2024

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

  • Cristina Martini,
  • Muhammad Idham Darussalam Mardjan and
  • Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

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Published 01 Aug 2024

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

  • Javier Gómez-Ayuso,
  • Pablo Pertejo,
  • Tomás Hermosilla,
  • Israel Carreira-Barral,
  • Roberto Quesada and
  • María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

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  • search of new bioactive compounds, as evidenced by the fact that they are present in many marketed drugs [1][2]. These substructures are found fused with other heterocycles in many cases, as illustrated by the antineoplastic dibromophakellstatin [3][4][5][6], the CDK inhibitor trilaciclib [7] or the
  • kinase inhibitor tinengotinib [8] (Figure 1). Despite the interest of these structures, several drawbacks are typically found during their syntheses, for instance the difficulty in obtaining certain functionalizations or the need of long, elaborated reaction sequences. In recent years, multicomponent
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Published 25 Jul 2024

Syntheses and medicinal chemistry of spiro heterocyclic steroids

  • Laura L. Romero-Hernández,
  • Ana Isabel Ahuja-Casarín,
  • Penélope Merino-Montiel,
  • Sara Montiel-Smith,
  • José Luis Vega-Báez and
  • Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

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  • synthesized similarly and their evaluation as inhibitors of the same enzyme [41][42], many of which demonstrated activity comparable to the inhibitor RM-532-105 [43]. In 2018, Merino-Montiel and Montiel-Smith prepared spiro 1,3-oxazolidin-2-ones (spirocarbamates) and a series of spiro 2-substituted amino-4,5
  • , the compounds demonstrated significant acetylcholinesterase inhibitory activity, with IC50 values ranging from 0.35 to 0.50 µM compared to the reference inhibitor tacrine (IC50 value = 0.29 µM). In 2016, El-Shahawi et al. presented the synthesis of novel spiro 1,3-thiazolidin-4-one derivatives at the
  • as a 17β-HSD3 inhibitor [42]. The same research group reported a new family of 3-spiromorpholinones derived from ADT bearing hydrophobic substituents [43][62]. The synthetic key step involved a regioselective aminolysis of the oxirane 131 with different ʟ- or ᴅ-amino acids (53–99% yields) to obtain
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Published 24 Jul 2024

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

  • Maria-Paula Schröder,
  • Isabel P.-M. Pfeiffer and
  • Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

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  • a class I SAM-dependent MT. The closest structural homologues with defined biosynthetic pathways are CcbJ and KedS8. These enzymes N-methylate the antibiotic lincosamide celesticetin and the anticancer protein kedaricidin, respectively. Crocagin A is a potent inhibitor of the RNA binding protein
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Published 18 Jul 2024

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

  • Kazuyuki Sato,
  • Satoki Teranishi,
  • Atsushi Sakaue,
  • Yukiko Karuo,
  • Atsushi Tarui,
  • Kentaro Kawai,
  • Hiroyuki Takeda,
  • Tatsuo Kinashi and
  • Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

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  • heterocyclic or aliphatic bromides scarcely proceeded. A Rh(III)–bis(aryl) complex, which might be formed from RhCl(PPh3)3 and the aryl Grignard reagents, plays an important role in giving the homo-coupling products in this reaction. Furthermore, we applied the reaction to the synthesis of a novel inhibitor
  • for integrins which is critical for several diseases. Keywords: biphenyltetracarboxylic acid; homo-coupling; integrin inhibitor; rhodium catalyst; Ullmann-type reaction; Introduction The Ullmann reaction is a coupling reaction of aryl halides using copper, traditionally using metallic copper-bronze
  • developing novel inhibitors of integrin function, we identified a drug candidate (10n) through high throughput screening (HTS) that inhibits the integrin complex formation, which is an important step for integrin activation. The binding inhibitor 10n was effective as IC50 of 190 μM in AlphaScreen system, and
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Published 12 Jun 2024

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

  • Maksim V. Kvach,
  • Stefan Harjes,
  • Harikrishnan M. Kurup,
  • Geoffrey B. Jameson,
  • Elena Harjes and
  • Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

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  • characterised as the most potent inhibitor of human CDA, but the quick degradation in water limited the applicability as a potential therapeutic. To improve stability in water, we synthesised derivatives of phosphapyrimidine nucleoside having a CH2 group instead of the N3 atom in the nucleobase. A charge
  • development of more potent CDA and APOBEC3 inhibitors. Keywords: APOBEC3; cytidine deaminase; enzyme activity; inhibitor; nucleoside; nucleotide; zebularine; Introduction Spontaneous hydrolytic deamination of cytosine to uracil (Figure 1A) is very slow under ambient conditions [1], but it is greatly
  • . Recently, a combination of the CDA inhibitor (4R)-2′-deoxy-2′,2′-difluoro-3,4,5,6-tetrahydrouridine (cedazuridine, Ib, Figure 1B) with the anticancer drug decitabine was approved as an oral pill (i.e., C-DEC or ASTX727) for the treatment of patients with intermediate or high-risk myelodysplastic syndrome
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Published 15 May 2024

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

  • Vladislav V. Nikol’skiy,
  • Mikhail E. Minyaev,
  • Maxim A. Bastrakov and
  • Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

Graphical Abstract
  • inhibitor of homeodomain-interacting protein kinases (HIPKs) [32], and combretastatin A-4 analogs evaluated for their anticancer properties against a panel of 60 human cancer cell lines [33] (Figure 2). The structures of all new compounds were confirmed by 1H and 13C NMR and HRMS. X-ray diffraction studies
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Published 14 May 2024

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

  • Luca Julianna Tóth,
  • Kateřina Krejčová,
  • Milan Dejmek,
  • Eva Žilecká,
  • Blanka Klepetářová,
  • Lenka Poštová Slavětínská,
  • Evžen Bouřa and
  • Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

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  • . One of the most targeted RNA viruses of the last years is, without doubt, SARS-CoV-2, the cause of the recent COVID-19 pandemic. HeE1-2Tyr, a known inhibitor of flaviviral RdRp, has been discovered to also have antiviral potency against this coronavirus. In this study, we report three distinct
  • : antivirotics; nonnucleotide inhibitor; RNA-dependent RNA polymerase; SARS-CoV-2; Introduction Epidemics caused by various viral infections, such as AIDS, Zika fever, Dengue fever, or Ebola, are a constant threat to communities of all sizes [1]. The COVID-19 pandemic, caused by the newly emerged severe acute
  • the polymerase, not only across the CoV group but also in other RNA viruses [13]. A great example of this phenomenon is remdesivir, which was originally developed as a therapeutic agent against Ebola virus [18][19]. HeE1-2Tyr (1) was originally identified by Tarantino et al. [20] as a potent inhibitor
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Published 06 May 2024

Carbonylative synthesis and functionalization of indoles

  • Alex De Salvo,
  • Raffaella Mancuso and
  • Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

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  • tm-phen (0.7–2 mol %) for others, 14 indole derivatives were isolated with yields of up to 100%. Among the 14 examples is a more soluble derivative of a KDR kinase inhibitor identified by researchers from Merck for blocking tumor-induced angiogenesis [31] (Scheme 13). An interesting synthesis of 3
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Published 30 Apr 2024

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

  • Arnaldo G. de Oliveira Jr.,
  • Martí F. Wang,
  • Rafaela C. Carmona,
  • Danilo M. Lustosa,
  • Sergei A. Gorbatov and
  • Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

Graphical Abstract
  • followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the
  • inhibitor (R)-rolipram (5b) [15], and the commercial drug (R)-baclofen hydrochloride (6), used to treat muscle spasticity from spinal cord injury and multiple sclerosis [16]. Results and Discussion Desymmetrization of N-protected 2,5-dihydro-1H-pyrroles Some initial results and reaction optimization Based
  • Supporting Information File 1 for details). Given the presence of the 4-aryl-γ-lactam motif in the phosphodiesterase-4 inhibitor rolipram, and in a synthetic intermediate for the baclofen drug, the Heck products 4bg and 4bq were used as starting material for their syntheses. N-Tosylated lactams 4bg and 4bq
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Published 29 Apr 2024

(Bio)isosteres of ortho- and meta-substituted benzenes

  • H. Erik Diepers and
  • Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

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  • ]. The ability of 1,5-BCHeps to act as bioisosteres of meta-benzenes was also studied by Anderson and co-workers. They reported the comparison of fatty acid amide hydrolase inhibitor URB597 with its 1,5-BCHep isostere 146 (Figure 21) [27]. They found that while replacement of one of the meta-benzenes
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Published 19 Apr 2024

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

  • Fumito Sato,
  • Terutaka Sonohara,
  • Shunta Fujiki,
  • Akihiro Sugawara,
  • Yohei Morishita,
  • Taro Ozaki and
  • Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

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  • inhibitor aphidicolin [28] and a ribosome-targeting antibiotic pleuromutilin [29] (Figure 1), they remained as underexplored targets in genome-mining approaches. In this study, we examined the biosynthetic genes for LRDs and identified two TCs consisting of αβ and αβγ domains. Heterologous expression in
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Published 03 Apr 2024

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

  • Jia Tang,
  • Yixiang Zhang and
  • Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

Graphical Abstract
  • secondary metabolites, filamentous fungi stand out as the most prolific producers of meroterpenoids [1][2][3]. Representative fungal meroterpenoids of medicinal importance include pyripyropene A, a cholesterol acyltransferase inhibitor [4]; fumagillin, an antimicrobial agent [5]; and mycophenolic acid, a
  • strong inosine 5-monophosphate dehydrogenase inhibitor [6]. The biosynthesis of fungal meroterpenoids has garnered interest in the organic chemistry field due to their structural complexity and associated intriguing enzymatic reactions and has thus been extensively researched for over a decade, providing
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Published 20 Mar 2024

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

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  • antagonist 7 [33], and aldosterone synthase inhibitor 8 [34]) as well as natural products (e.g., new alkaloids deoxytryptoquivaline and deoxynortryptoquivaline from fungus Aspergillus clavatonanicus identified as natural cardiomyocyte-protective agents against cold ischemic injury [35] and possible natural
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Published 11 Mar 2024

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

  • Jens Frackenpohl,
  • David M. Barber,
  • Guido Bojack,
  • Birgit Bollenbach-Wahl,
  • Ralf Braun,
  • Rahel Getachew,
  • Sabine Hohmann,
  • Kwang-Yoon Ko,
  • Karoline Kurowski,
  • Bernd Laber,
  • Rebecca L. Mattison,
  • Thomas Müller,
  • Anna M. Reingruber,
  • Dirk Schmutzler and
  • Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

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  • binding affinity to enzyme targets, e.g., acyl-ACP thioesterases, belonging to the protein family of FATs, was demonstrated by using co-crystallization, fluorescence-based thermal shift assays, and chemoproteomics techniques [3]. Likewise, methiozolin (2) is a recently assigned FAT inhibitor that has
  • lead structure with ample space for structural variations. By formally replacing one pyridine moiety of 1,8-naphthyridine 4 by a five-membered thiazole unit, we have identified thiazolo[4,5-b]pyridine 5 as a strong inhibitor of acyl-ACP thioesterase, which has further been confirmed via an X-ray co
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Published 01 Mar 2024

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

  • Fumihiro Ishikawa,
  • Sho Konno,
  • Hideaki Kakeya and
  • Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

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  • -domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we
  • investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S
  • synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors. Keywords: adenylation domain inhibitor; gramicidin S synthetase; natural product; nonribosomal peptide; nonribosomal peptide synthetase
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Published 26 Feb 2024

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

  • Yumei Wang,
  • Guangzhu Wang,
  • Yanping Zhu and
  • Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

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  • SHP2 inhibitor that has entered phase II clinical trials for the treatment of solid tumors and has been approved by the FDA as a rare drug for treating esophageal cancer (Figure 1) [4]. Among the fluoroalkyl moieties, the geminal difluoromethylene group has showcased its beneficial properties as an
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Published 01 Feb 2024

Anion–π catalysis on carbon allotropes

  • M. Ángeles Gutiérrez López,
  • Mei-Ling Tan,
  • Giacomo Renno,
  • Augustina Jozeliūnaitė,
  • J. Jonathan Nué-Martinez,
  • Javier Lopez-Andarias,
  • Naomi Sakai and
  • Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

Graphical Abstract
  • increased activity to A/D49/23 = 2.0. Suppression of this increase in a virtual complex 50 with a competitive inhibitor 51 further supported that the observed activity originates from anion–π catalysis. With A/D52/23 = 1.3, pristine MWCNTs 3 failed to increase the activity of TEA 23 much more than SWCNTs 2
  • MWCNT 53 with inhibitor 51 in complex 54 was supported by a drop from A/D53/23 = 7.3 to A/D54/23 = 4.8. Under identical conditions, the much more π-basic inhibitor 55 inhibited enolate addition by the MWCNT 53 almost completely, i.e., A/D56/23 = 1.9 for the formal catalyst-inhibitor complex 56
  • . Increasing inhibition with the π basicity of the inhibitor was consistent with powerful anion–π interactions accessible on MWCNTs for efficient anion–π catalysis. Like in the fullerene series, elongation of the tether in 57 decreased catalytic activity to still important A/D57/23 = 5.0, presumably due to
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Published 12 Dec 2023

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

  • Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

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  • reported as inhibitor of chikungunya virus (IC50 of 3.6 µM) [4] whereas 3-nitrobenzylidenerhodanine (C) displayed a very potent antitubercular activity with a MIC of 0.05 µg/mL (compared to streptomycin MIC of 6.25 µg/mL) [5]. 5-Benzylidenerhodanine derivatives also constitute interesting starting
  • -competitive PI3Kγ inhibitors [7]. A few years ago, we worked intensively on 2-heteroarylimino-1,3-thiazolidin-4-ones as potential antitumor agents [8] and we demonstrated that derivative F was an interesting CDC25A inhibitor [9]. Up to now, the synthesis of most organic compounds still uses harmful reagents
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Published 04 Oct 2023

Synthesis of ether lipids: natural compounds and analogues

  • Marco Antônio G. B. Gomes,
  • Alicia Bauduin,
  • Chloé Le Roux,
  • Romain Fouinneteau,
  • Wilfried Berthe,
  • Mathieu Berchel,
  • Hélène Couthon and
  • Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

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Published 08 Sep 2023

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

  • Valeriy O. Filimonov,
  • Alexandra I. Topchiy,
  • Vladimir G. Ilkin,
  • Tetyana V. Beryozkina and
  • Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

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  • exhibit a variety of biological activity. Their application is known in pharmacy [1][2][3][4] and agro-industry [5][6][7][8]. Especially such compounds are used to protect plants from insects and weeds (Figure 1). Thus, pinoxaden is a commercially available inhibitor of acetyl-CoA carboxylase and affects
  • the biosynthesis of fatty acids in plants, which leads to herbicidal activity [9]. Pyraclonil is used as a protoporphyrinogen oxidase inhibitor for weed control. Such inhibitors not only block the production of chlorophyll and gem in plant pests, but also lead to the formation of highly reactive
  • molecules that attack and destroy lipids and protein membranes of weed cells [10]. Fipronil is an inhibitor of GABA receptors and affects the nervous system of insects as a broad-spectrum insecticide [11][12]. On the other hand, thioamides are an important class of organic compounds. 6-Thioguanine and
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Published 08 Aug 2023

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

  • Vladislav Yu. Shuvalov,
  • Ekaterina Yu. Vlasova,
  • Tatyana Yu. Zheleznova and
  • Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

Graphical Abstract
  • -aryl-substituted derivatives should be distinguished, exhibiting antiviral [13] and anti-inflammatory properties [14], being modulators of estrogen-related receptor alpha [15], JAK1 kinase inhibitor [16], GSK3 [17] and GyrB [8] inhibitors (Figure 1). Despite the high demand, their synthesis methods are
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Published 02 Aug 2023
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  • antibacterial acitivity against resistant S. aureus strains. It is also an inhibitor of the enzyme peptide deformylases (PDFs). The synthesis comprised the reaction between the highly substituted hydroquinone 142 and dehydroalanine 143 in the presence of chiral phosphoric acid P7 as catalyst to prepare
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Published 28 Jun 2023

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

  • Yuan-Nan Yuan,
  • Jin-Qiang Li,
  • Hong-Bin Fang,
  • Shao-Jun Xing,
  • Yong-Ming Yan and
  • Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

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  • (LPS, 1 μg/mL) for 12 h. Subsequently, radioimmunoprecipitation assay (RIPA) buffer (Beyotime, PR China) containing a protease inhibitor (Roche, Germany) was used to extract total protein from cells. Protein content samples was determined by the BCA assay (Thermo, USA). Equivalent protein extracts were
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Published 07 Jun 2023
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