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Search for "inhibitors" in Full Text gives 480 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Cross metathesis-mediated synthesis of hydroxamic acid derivatives
Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285
- advantage. In continuation of our earlier studies [26][27] on HDAC inhibitors, we herein report a direct access to α,ß-unsaturated hydroxamates through cross-metathesis reaction. Results and Discussion It is known that a CM reaction between a class-I olefin and a class-II olefin proceeds better in the
- of the important cyclic peptide Chap-31 may encourage the preparation of cyclic peptide based HDAC inhibitors. The developed methodology may hence complement the existing literature on the preparation of such class of compounds and may find applications. Experimental General procedure for cross
Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum
Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277
- mycotoxins [2], a class of highly bioactive secondary metabolites that belong to the strongest known inhibitors of protein biosynthesis in eukaryotes [3]. Similarly, the sesquiterpene aristolochene (2) is the parent hydrocarbon of PR toxin [4][5] and has been used as a marker to differentiate between toxin
Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process
Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269
- ]pyridine has been reported as inhibitors of cytochrome P450 [33]. Furthermore, muscopyridine is being used in perfume industry [34]. Among the several methods available for the synthesis of pyridines or cycloalkyl-fused pyridines [23][24][25][26][27][35][36][37][38][39][40][41][42][43][44], the one-pot
Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics
Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267
- to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could
- interface in both Gram-negative and Gram-positive microorganisms. In order to encourage prospective drug discovery endeavours in this field, this study focuses on four examples of bacterial PPIs for which inhibitors with promising activities have been reported. For each of the targets the structural
- (bromodomain and extra terminal) molibresib (4, Figure 2), developed by GSK and currently in phase I for the treatment of several carcinomas [30]. It is also worth highlighting two PPI inhibitors that have recently been approved: lifitegrast (5, Figure 2) is an anti-inflammatory integrin antagonist that
Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis
Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265
- active site from the protein easier as compared to supramolecular anchoring. However, the design of catalysts capable of undergoing dative anchoring is usually based on interactions of inhibitors with the active site of the protein. This makes the catalyst design challenging and the application is
Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors
Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262
- the test compounds inhibited the STS markedly. The structure–activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17β-HSD1 enzyme with submicromolar IC50 values. Dual OATP2B1 and 17β-HSD1 inhibitors have been identified. Keywords: catalysis
- estrone derivatives, including estrone-3-sulfate could be blocked. Inhibitors based on the estrane core could have multiple inhibitory properties concerning the two enzymatic steps of the sulfatase pathway and OATP2B1-mediated membrane transport of estrone-sulfate. The inhibitor design is usually based on
- the substrate of the target protein. The literature reveals diverse synthetic estrone derivatives as STS or 17β-HSD1 inhibitors [1][14], but to the best of our knowledge, there are no reports on estrone-based OATP2B1 inhibitors. Note that estrone itself has been shown to slightly inhibit estrone-3
Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus
Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260
- product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was
Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid
Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252
- neurodegenerative diseases [30]. Therefore, the study and development of tyrosinase inhibitors from renewable resources is of particular interest for research and industry [31][32]. Fu et al. investigated naturally occurring ginkgolic acids which they selectively synthesized from 2,6-dihydroxybenzoic acid (4), and
Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis
Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246
- -known biologically active analogs (Scheme 5) [3]. Pd-catalyzed reactions were effected on bromotriazolochromene 5e. The piperazin-1-ylchromenes have been identified to be potent inhibitors at the 5-HT1A receptor and at the 5-HT transporter [45][46]. Thus, Buchwald–Hartwig amination of 1-phenylpiperazine
Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium
Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243
- against the EC90 of (enantiopure) L-OOHL (10 nM). Only 4 compounds (3% of the library) were able to inhibit SdiA activity in S. Typhimurium by greater than 65% under these conditions (Figure 2). This is a lower percentage of inhibitors than we typically identify for this AHL analog library, even with the
- compounds, R8 displayed the greatest inhibitory activity in SdiA – inhibition to 120% with an IC50 of 44 μM. Interestingly, similar compounds with shorter tail lengths are potent inhibitors in other receptors: R6, with a 9-carbon tail, is a potent inhibitor of QscR and LasR, and Q9, with an 8-carbon tail
Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers
Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241
- coordinate population-wide group behaviours in the infection process like concerted secretion of virulence factors. One very important signalling network is the Pseudomonas quinolone signal (PQS) QS. With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the
- network with compensatory mechanisms ensuring environmental adaptability and fine-tuned control of associated virulence genes (Figure 1). All four have been studied in the pursuit of quorum sensing inhibitors (QSI) to be used as blockers of P. aeruginosa pathogenicity [11][23]. Typically, a QS system of
- treatment. PqsA inhibitors Anthranilic acid analogues Since anthranilic acid (1) serves as a PqsA substrate, the first compound reported to inhibit PqsA is 6-FABA (2, Figure 3), which was able to block this enzyme and successfully suppressed the production of DHQ in PA14 strains at a rather high
Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections
Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239
- potential (RIP), which is benchmarked with the reference methyl α-D-mannoside (1a) defined as RIP = 1, was increased up to 6900-fold [17]. The biphenyl mannosides (e.g., 4, 5) have subsequently been identified by the Ernst and Hultgren/Janetka groups as promising inhibitors of FimH-mediated bacterial
- that are interconnected by a hinge region. Interestingly, in vitro binding studies have been performed with the lectin domain only. Recent works suggested that the conformation of the two domains influence the protein’s affinity towards inhibitors and the biologically relevant state is a matter of
- , Titz et al. have developed small molecule LecB inhibitors derived from mannose and obtained potent monovalent inhibitors (compound 15) of LecB-mediated bacterial adhesion [47]. The sulfonamide 15 and cinnamide 16 were developed to take advantage of interactions with a nearby shallow pocket, and indeed
Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase
Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231
- widely accepted hypothesis. AChE inhibition can increase ACh levels in the synaptic clefts and then alleviate the cognitive deficit in AD patients. The design of novel acetylcholinesterase inhibitors (AChEIs) has been mostly based on a dual-binding site strategy whereby the designed molecules
- well as with benzylpyridinium moieties [12][13][14] have been reported as dual-binding site AChE inhibitors. Recently we have reported the AChE inhibitory activity of the coumarin derivative, scopoletin conjugated with a pyridinium side chain (Figure 1) [15] and a docking study revealed that the
- scopoletin portion of the compound binds to amino acid residues in PAS, whereas the N-benzylpyridinium moiety binds to those present in the CAS of AChE. To develop potent AChE inhibitors, we were interested in aminocoumarin as a replacement of scopoletin due to the presence of the amino group in the former
Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives
Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229
- integration of viral DNA into host cell chromatin (Figure 1) [7][8][9]. In contrast to the FDA approved integrase strand transfer inhibitors (INSTIs) dolutegravir, elvitegravir, and raltegravir, arylquinolines 1 and 2 bind to a non-catalytic site of integrase (NCINI) via allosteric binding inhibition
- [C13H12BrNO3 + Na]+ 331.989277; found: 331.988788; anal. calcd for C13H12BrNO3: C, 39.70; H, 1.67; found C, 39.51; H, 1.74. Investigational non-catalytic HIV-1 Integrase inhibitors. Boehringer Ingelheim retrosynthesis of quinoline 1. Quinoline ring condensation strategies. Isatoic anhydrides from anthranilic
Synthesis of dihydroquinazolines from 2-aminobenzylamine: N3-aryl derivatives with electron-withdrawing groups
Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227
- pharmacological interest. For example, vasicine is a 3,4-dihydroquinazoline alkaloid isolated from natural sources with antitumor activity [1]. Vasicine and deoxyvasicine are also potent butyrylcholinesterase (BChE) inhibitors [2]. Some synthetic derivatives containing the dihydroquinazoline scaffold have shown
- antimicrobial [3] and antifungal properties [4]. In addition, antiparasitic activity has been studied for some members of this family as inhibitors of trypanothione reductase [5], an essential enzyme of the kinetoplastid Trypanosoma brucei. Their activity as selective T-type calcium channel blockers [6][7][8][9
- ][10][11], as tumor suppressors [12] and as neuroprotective agents has also been reported [13]. Some related 2-amino-DHQs were studied as blood platelet aggregation inhibitors [14], antihypertensive agents [15] or inhibitors of β-secretase, an important target for Alzheimer’s disease [16]. Additionally
Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids
Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226
- Dau) had a synergistic effect with histone deacetylase inhibitors (e.g., prodrug of butyric acid) in several malignant cell lines [38]. This finding could also be a possible explanation for the increased cytotoxic effect of the conjugates containing acylated Lys compared to the parent one. Involvement
- could play a significant role in the antitumor activity of a drug-containing conjugate [40]. The association of PI3K activation with the antitumor activity of the conjugates was determined by pretreating the cells with PI3K inhibitors (wortmannin – W and LY294002 – LY). The antitumor effect of the
- conjugates and Dau on the cells pretreated with PI3K inhibitors or with DMSO (solvent of the inhibitors) was assessed by an alamarBlue-assay after 48 h of incubation. The results of the PI3K-assay were given by calculating the inhibition index as the ratio of the viability of the pretreated and control (DMSO
Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases
Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189
- target GMIIb enzyme. In contrast, no inhibition effect of the pyrrolidines against LManII was observed. The modification of the imino-L-lyxitol core is therefore a suitable motif for the design of inhibitors with desired selectivity against the target GMIIb enzyme. Keywords: azasugars; hydrolases
- ; inhibitors; pyrrolidines; synthesis; Introduction Carbohydrates as chiral templates for a construction of bioactive compounds are of steady interest in medicinal chemistry [1][2][3]. The polyfunctional nature of carbohydrate units offers many possibilities for the design of a wide variety of new compounds
- progress of tumor growth and metastasis. However, all potent GMII inhibitors, including swainsonine, showed also an undesired co-inhibition of lysosomal α-mannosidase (LM) that limits their use as therapeutic agents [25]. Since the discovery of swainsonine, new inhibitors of GMII that are based on its
Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions
Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161
- topoisomerase inhibitors [5]. More recently, much interest in this research area is focused on the non-canonical quadruplex DNA (G4-DNA) [6][7][8]. Mostly based on the principles and requirements of ligands that bind to duplex DNA, numerous G4-DNA ligands have been developed to study their selectivity and
Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases
Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147
- (quinoxaline fused by a six-membered heterocycle at the [a]-side) are promising biologically active compounds. Recent research studies revealed that they can act as inhibitors of poly(ADP-ribose) polymerase (PARP) [3], inhibitors of hepatitis C virus [4], 5-HT2C agonists [5][6][7], substances for controlling
β-Hydroxy sulfides and their syntheses
Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143
- ) origin as potential therapeutic agents is also well documented. For instance, Luly et al. synthesized β-hydroxy sulfides coupled to leucine-valine (Leu-Val) replacements as inhibitors of human renin in order to lower blood pressure [100][101]. The high activity of these compounds is attributed to the
- presence of the hydroxy functional group acting as a transition-state analog. The synthesis of the inhibitors commenced with the conversion of aldehyde 127 into alkene 128 via a Wittig reaction followed by epoxidation to furnish epoxide 129. Regioselective opening of the epoxide ring with a thiolate gave
- the N-Boc protected β-hydroxy sulfide 130 as a key intermediate. Deprotection of the Boc followed by the imidation of the free amine with protected dipeptides that mimic Leu-Val produced the inhibitors of human renin 131 as depicted in Scheme 44. Yoshioka and co-workers reported two synthetic routes
Anomeric modification of carbohydrates using the Mitsunobu reaction
Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138
- -protected reducing glucose derivative 2 gave the β-glucoside 76 with good stereoselectivity, and the respective mannose derivative 24 resulted in the pure α-mannoside 77 in good yield (Scheme 12) [56]. In a general approach to coumarin-derived inhibitors of gyrase B, a group working at Hoechst Marion
- implemented in the preparation of novobiocin analogues [65], and formed a key step in the synthesis of new glycosidic PDE4 (phosphodiesterase type 4) inhibitors [66]. Also calix[4]arenes could be selectively mono- or diglycosylated by means of the Mitsunobu methodology [67][68]. The Mitsunobu reaction was
- -dialkoxycarbonylhydrazines [84]. This anomeric N-phthalimidation was later implemented by Nishimura et al. for the iminosugar 114 with phthalimide to give 115 in a high yield, en route to a new family of α-L-fucosidase inhibitors (Scheme 21) [85]. More generally, the preparation of modified glycosylamines under Mitsunobu
Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)
Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132
- masked as a hemiketal in bafilomycins, e.g., in bafilomycin A1 [11][12][13][14]. Bafilomycins are a family of macrolide antibiotics isolated from actinobacteria such as Micromonospora and Streptomyces species [11]. They are specific inhibitors of vacuolar ATPase (V-ATPase) [15]. The most studied compound
- of this class, bafilomycin A1 (Figure 3) is a useful biochemical tool as it prevents the re-acidification of synaptic vesicles once they have undergone exocytosis [14]. Bafilomycins are also known to be cytotoxic, inhibitors of autophagy, active against Gram-positive bacteria, yeast and fungi
- . The inoculum was removed 4 hours later and monolayers were washed three times with PBS and overlaid with fresh medium containing no inhibitors. Infected cells were lysed 3 days later, and reporter virus infection was determined by renilla luciferase activity. The cell viability was measured by
[3 + 2]-Cycloaddition reaction of sydnones with alkynes
Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113
- acids – potent xanthine oxidoreductase inhibitors [40] or even 3,4-unsubstituted pyrazoles [16]. Both pyrazole carboxylic groups can be also modified to hydrazides and oxazole rings [26] or a new condensed pyridazine ring [27]. Less reactive dipolarophiles such as dibenzoylacetylenes (1,4-diphenylbut-2
Novel unit B cryptophycin analogues as payloads for targeted therapy
Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109
- glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. Keywords: cryptophycin; cytotoxic agents; novel payloads; tubulin inhibitors; tumour targeting; Introduction
- the other derivatives 23 and 24 (Figure 4). Besides hydrogen bond formation and binding affinity of inhibitors 2, 23 and 24, π-interactions and hydrophobic contacts with the binding pocket of the vinca domain were detected that would in turn increase the affinity of the inhibitor and its effect on the
A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols
Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105
- ] or vasodilating activities (II) [6]. Other ones have been reported as inhibitors of HIV-1 integrase and viral replication in cells [7] or antitubercular agents (III) [8][9]. Various diarylmethane-based molecules, like tolterodine (IV) [10], podophyllotoxin (V) [11] and lasofoxifene (VI) [12] have
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