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Search for "inhibitors" in Full Text gives 493 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
19F NMR as a tool in chemical biology
Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28
- reviewed in detail by Dalvit and Vulpetti [41][42]. The main advantages of these methods for lead compound screening is that they offer a platform not only for the rapid high-throughput screening of multiple protein small ligands, but also for the direct screening of functional inhibitors of much larger
- inhibitors in situ using 19F NMR spectroscopy (Figure 6). For this, the activity of the membrane-bound FAAH enzyme was evaluated by monitoring the hydrolysis of a fluorinated anandamide analogue ARN1203, a previously reported FAAH substrate, to arachidonic acid and 1-amino-3-fluoropropanol in the presence
- and absence of a broad range of known FAAH inhibitors with widely different potencies. The results clearly showed that the proposed n-FABS method was successful in detecting strong inhibitors of FAAH activity in cells. Also, it allowed the accurate quantification of the corresponding IC50 values, all
Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature
Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16
- present (Scheme 6). Conclusion In conclusion, we have developed novel, complementary multi-parallel synthetic routes permitting the exploitation of the C-3 then C-4 vectors or vice versa to deliver our library of novel 3,4-disubstituted pyridin-2(1H)-one kinase inhibitors starting from readily-available 2
Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives
Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242
- biological properties exhibiting enzymatic activity as potent and selective protease inhibitors, fungicidal and herbicidal activity [17], we designed an efficient, simple, and ecofriendly synthetic procedure for the preparation of new synthetic compounds containing joint phenothiazine/ferrocene and α-amino
Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles
Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241
- with aniline (1a) or amantadine in the presence of HATU or EDCI to form the multisubstituted pyrrole-3-carboxamide derivatives 4x and 4y (Scheme 4). These skeletons have been proven to be promising inhibitors for the production of cytokines [47]. A plausible mechanism for the model reaction was
Synthesis of purines and adenines containing the hexafluoroisopropyl group
Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224
- number of important drugs used in different therapeutic areas contain the benzimidazole ring […], such as proton pump inhibitors (omeprazole), antihypertensives (candesartan, telmisartan), antihistaminics (astemizole), antihelmintics (albendazole, mebendazole), as well as several other kinds of still
NMR Spectroscopy of supramolecular chemistry on protein surfaces
Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203
- interaction between the 14-3-3 protein and its phosphorylated cargo proteins [42][44][45]. Another ligand with just one GCP unit targets the central pore of the 14-3-3 dimer [43]. Unfortunately, these systems have not yet been studied by NMR. However, several other 14-3-3 inhibitors and stabilizers serve as
- signal intensities (tau bound by 14-3-3 compared to free tau) show a decrease for tau residues that are part of the 14-3-3 binding epitopes due to line broadening. In the presence of chimeric inhibitors, in which a small molecule was fused to a 14-3-3 binding peptide, the inhibitors target the unlabeled
- protein in unlabeled minimal media by simply adding the isotope-labeled amino acid, without the need for auxotrophic strains or metabolic enzyme inhibitors [108]. The assignment of all Lys residues, beyond the assignments available from classic uniform 15N- and 13C-labeling, was achieved by specific 15N
Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol
Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193
- use. Particularly, some enaminones I and II were found to show antioxidant [3], antimycotic [7][8], antimycobacterial [9][10], anti-Alzheimer’s disease (JNK3 inhibitors) [11], platelet aggregation inhibitory [12], antimicrobial [7] and analgesic [13] activities. Enaminones II were reported as
Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups
Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182
- give analogue 7b reduced the lipophilicity. Interestingly, while the nonfluorinated 7a and 7c diastereomers have different logD7.4 values, this is not the case for their fluorinated analogues 7b and 7d. Oxazine derivative 8 featured in the development of centrally active β-secretase (BACE1) inhibitors
Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst
Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179
- , spiropyranes, and stilbenes [2]. Diarylethenes were reported in the context of photoswitchable catalysis as inhibitors of the Karstedt´s catalyst [3] and for pKa modulation in acid–base-controlled processes [4]. Molecular motors for stereodivergent anion binding catalysis [5], azopeptides for the acetylation
Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale
Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177
- (Dothideomycetes) were reported as intercellular adhesion molecule-1 (ICAM1) expression inhibitors in a patent literature [28]. Therefore, the presence of the 2,4-dimethyl-3-hydroxyhexanoate moiety may be a potential chemical marker for Dothideomycetes, although this is difficult to conclude due to the fact that
Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction
Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174
- Micromonospora [5]. Dipeptide analogs with phosphonoproline 2 and piperidine-2-phosphonic acid 3 are potent inhibitors of dipeptidyl peptidase IV [6][7]. Oxygen-containing heterocycles containing a phosphoryl group are also of interest in the development of new drugs. It is known that phosphorylated carbohydrate
- analogues 4 and 5 are neuraminidase inhibitors (Figure 1) [8][9]. These circumstances create an interest in discovering synthetic routes for obtaining nonracemic phosphoryl-substituted heterocycles. Thus, in recent years, effective methods for the asymmetric synthesis of chiral phosphonates containing
Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides
Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167
- recorded for microtiter plates with hundreds to thousands of wells. This standard HT screening provides access to quantitatively reliable curves for the dependence on the concentration, incubation time, activators, inhibitors, and so on within a reasonable time. High-content screening (HCS) combines this
Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2
Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152
- site of GlfT2, none of these compounds serve as efficient inhibitors of the enzymes involved in the mycobacterial galactan biosynthesis. Keywords: GlfT2; molecular modeling; mycobacterium tuberculosis; synthesis; transition state inhibitors; Introduction Tuberculosis (TB) is one of the most prevalent
- silico based design of possible GlfT2 inhibitors that mimic the TS structure. The galactofuranosyltransferase GlfT2 is a bisubstrate enzyme with a single catalytic domain and its catalytic reaction transition state shares some structural similarities with the previously modeled N
- -acetylglucosaminyltransferase I (GnT-I) reaction transition state [11]. Previously, we have designed 2-thiohexofuranoside skeletons bearing a phosphate group in position 1 by molecular modeling as potential transition state inhibitors of human glycosyltransferase I (GnT-I) [12], the bisubstrate enzyme requiring a metal co
One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway
Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148
- (trade name Sivextro), which exhibits antibiotic activity is another oxazolidinone drug approved by the FDA in 2014 [11]. Befloxatone and toloxatone, N-substituted phenyloxazolidinone derivatives, are reversible inhibitors of monoamine oxidase (MAO) [12][13]. N-Aryloxazolidinedione compounds, which are
Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach
Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134
- inhibitors based on the tripeptide sequence Arg–Gly–Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner–Wadsworth–Emmons olefination, diimide reduction, and global deprotection to synthesise
- ; Introduction Tetrahydronaphthyridines are prominent in peptidomimetic pharmaceuticals as arginine mimetics and they are widely used in Arg–Gly–Asp (RGD) peptide mimetics such as αv integrin inhibitors [1]. Tetrahydronaphthyridines represent less basic but more permeable alternatives to arginine (pKa ≈ 7 versus
- 13.8) [1] replicating the side-on salt-bridge binding interaction made between the guanidinium functionality of arginine and an aspartic acid residue in the protein. Consequently, this moiety has been used in various integrin inhibitors (Figure 1) [2][3][4][5][6][7][8]. Current routes to install
4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity
Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124
- rutaceous plants [9]. Examples from microbes include chymase inhibitors SF2809-I to VI from an actinomycete of the genus Dactylosporangium [10], a quorum sensing signaling molecule 2,4-dihydroxyquinoline (DHQ, 4) from Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia thailandensis, [7], and 4-O
One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions
Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120
- anticancer [10][11], antimicrobial [12], antiviral agents [13][14], and eosinophilia inhibitors [15]. Therefore, it is highly desirable to develop efficient and practical synthetic methods for triazinethione architectures and to expand the structure diversity of this class of compounds for medicinal
The McKenna reaction – avoiding side reactions in phosphonate deprotection
Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119
- Michael acceptor, as such is currently popular in the development of covalent inhibitors [43]. The reaction was carried out in the presence of 12 equiv BTMS at 35 °C. The disappearance of the signals originating from the vinyl protons (multiplets at δ 5.56–5.66 and 5.95–6.10 ppm) and the appearance of the
Recent synthesis of thietanes
Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116
- discovery of pan-CDK inhibitors. For this, 3-bromo-2,2-bis(bromomethyl)propan-1-ol (20) was transformed into 3-bromomethyl-3-hydroxymethyl-1-tosylazetidine (21), which was treated with Ph3P/CBr4 to yield 3,3-bis(bromomethyl)-1-tosylazetidine (22) in 52% yield. The double displacement of 3,3-bis(bromomethyl
- -2,4-diol and treated it with sodium sulfide to afford 2,4-di(benzyloxymethyl)thietane (49). Compound 49 was then further transformed into two different anomeric thietanose nucleosides 1 and 50 [4] (Scheme 11). In the development of novel class I phosphoinositide 3-kinase (PI3k) inhibitors, 6-bromo-3,3
Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors
Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108
- ]. Specifically, bisphosphonates act as osteoclast resorption inhibitors, augmenting the bone density and preventing osteoporosis [4]. Moreover, some bisphosphonates have gained attention as potential antiinflammatory agents by in vitro and in vivo assays [5][6][7][8]. Additionally, bisphosphonates have been
- molecular docking studies were performed to account for a possible action mechanism as MMP-8 and MMP-9 inhibitors. Results and Discussion Chemistry As part of our ongoing interest in the discovery of new antiinflammatory agents, our research group have previously addressed the synthesis and in vivo
- mechanism of action of the bisphosphonates 3–6, we propose that the tested derivatives are acting as MMP inhibitors. In this respect, MMP-8 and MMP-9 isoenzymes are related to inflammatory processes in different tissues [32][33][34][35]. Furthermore, for MMP-8 and MMP-9, enzyme–inhibitor interaction modes
Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions
Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106
- crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also
Anthelmintic drug discovery: target identification, screening methods and the role of open science
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- developed helminth analysis methods using CellProfiler. A virtual screening approach was used to identify inhibitors of S. mansoni thioredoxin glutathione reductase [140]. These virtual hits were then tested in a CellProfiler-based high content screen using S. mansoni schistosomula, which determines both
Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore
Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98
- in the last few years due to the discovery that truxillic acid derivatives are inhibitors of FABP (fatty acid binding proteins), which are responsible for the cellular reuptake of anandamide, an endocannabinoid neurotransmitter, and that they can be involved in a very efficient treatment for chronic
A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes
Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96
- the HRMS measurements is appreciated. Funding The University of Zagreb short term scientific support under the title “Synthesis and functionalization of novel (hetero)polycyclic photoproducts as cholinesterase inhibitors” is gratefully acknowledged.
Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones
Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95
- active small molecules that exhibit antihypertensive activity [7][8]. Moreover, these heterocycles can be used as 5-HT3 antagonists [9], rho kinase inhibitors [10], thymidylate synthetase inhibitors [11], PARP-1 inhibitors [12], melatonin MT1 and MT2 receptor agonist [13], and fascin-targeted
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