68790-38-5Relevant articles and documents
The preparation of fluorescence-quenched probes for use in the characterization of human factor Xa substrate binding domains
Bromfield, Karen M.,Cianci, Julia,Duggan, Peter J.
, p. 427 - 439 (2004)
The preparation and characterization by LCMS of a library of 55 fluorescence-quenched peptides is described. The peptides bear a terminal anthranilamide fluorophore and a penultimate 2,4-dinitrophenyl-L-lysine quencher, and will be used to probe the subst
TELOMERASE REVERSE TRANSCRIPTASE DEGRADERS AND METHODS OF USE THEREOF
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, (2020/12/30)
The present disclosure provides TERT inhibitor compounds, a TERT inhibitor linked to a ubiquitin ligase ligand, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of inhibiting telomerase reverse transcriptase (TERT) and methods of treating or preventing a disease or disorder using said compounds and/or compositions.
Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases
Millies, Benedikt,Von Hammerstein, Franziska,Gellert, Andrea,Hammerschmidt, Stefan,Barthels, Fabian,G?ppel, Ulrike,Immerheiser, Melissa,Elgner, Fabian,Jung, Nathalie,Basic, Michael,Kersten, Christian,Kiefer, Werner,Bodem, Jochen,Hildt, Eberhard,Windbergs, Maike,Hellmich, Ute A.,Schirmeister, Tanja
, p. 11359 - 11382 (2019/12/24)
The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the molecules were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modification of the obtained cysteine mutants with maleimides, followed by computational elucidation of the possible binding modes. In infected cells, antiviral activity against Dengue virus serotype 2 using prodrugs of the inhibitors was observed. In summary, a novel inhibitor scaffold targeting an allosteric site shared between flaviviral NS2B/NS3 proteases is presented whose efficacy is demonstrated in vitro and in cellulo.
COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
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Paragraph 0354, (2016/10/27)
PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
Of the skeleton with dithiazo Pleuromutilin derivatives and the preparation method, application
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Paragraph 0092; 0093; 0095, (2016/12/01)
The invention discloses a pleuromutilin derivative with a thiadiazole skeleton and a preparation method thereof. The preparation method comprises the following steps: 1, synthesizing 22-O-(4-tosyl)acetoxyl mutilin; 2, synthesizing 14-O-( iodoacetyl)mutili
Novel derivatives of 5-amino-1-cyclopropyl-7-[(3R,5S)3,5- dimethylpiperazine-1-yl]-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid: Their synthesis, antimicrobial, antifungal, and urease inhibitory studies
Arayne, M. Saeed,Sultana, Najma,Gul, Somia,Khan, Ajmal
, p. 1248 - 1256 (2014/03/21)
Sparfloxacin (SPFX) or 5-amino-1-cyclopropyl-7-[(3R,5S)3,5- dimethylpiperazine-1-yl]-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid is an orally active synthetic, broad spectrum third generation quinolone, with excellent activity against Gram-positive bacteria with selectivity against anaerobes and atypical pathogens. Three derivatives of SPFX (2, 3, and 4) were synthesized by reacting different aromatic carboxylic acids with SPFX (1). Chemistry involved the formation of amide between reacting species through nucleophilic substitution reactions. The synthesized derivatives were then structurally characterized by IR, NMR, and mass spectroscopic techniques. The antimicrobial activities of these derivatives were evaluated against four Gram-positive, seven Gram-negative bacteria, and six fungi, using SPFX as a reference. Statistical analysis revealed these derivatives as active antimicrobial agents, and 2 was more potent antimicrobial agents than the parent drug as well other fluoroquinolones. Compounds 3 and 4 showed a significant activity against Fusarium solani. Moreover, these three derivatives were evaluated for inhibitory activities against enzyme urease, carbonic anhydrase II, and α-chymotrypsin. Results showed their selectivity against urease enzyme. Based on their nontoxic behavior, these derivatives may be potential agents for further studies.
DIHYDROQUINAZOLINONE ANALOGUES AS BRD4 INHIBITORS
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Page/Page column 46-47, (2014/10/15)
The present invention encompasses compounds of general formula (I) wherein the groups R1 to R4 and A1 to A5 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
DIHYDROQUINAZOLINONE ANALOGUES
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Paragraph 0211; 0212, (2014/10/16)
The present invention encompasses compounds of general formula (I) wherein the groups R1 to R4 and A1 to A5 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
Synthesis and biological activities of novel pleuromutilin derivatives with a substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors
Shang, Ruofeng,Pu, Xiuying,Xu, Ximing,Xin, Zhijun,Zhang, Chao,Guo, Wenzhu,Liu, Yu,Liang, Jianping
, p. 5664 - 5678 (2014/08/05)
A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution method and Oxford cup assay. The majority of the tested compounds displayed moderate antibacterial activities. Importantly, the three compounds with amino or tertiary amine groups in their side chains, 11, 13b, and 15c, were the most active antibacterial agents. Docking experiments carried out on the peptidyl transferase center (PTC) of 23S rRNA proved that there is a reasonable direct correlation between the binding free energy (ΔGb, kcal/mol) and the antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in rat were characterized by moderate clearance and oral bioavailability.
Ester vs. amide on folding: A case study with a 2-residue synthetic peptide
Vijayadas, Kuruppanthara N.,Nair, Roshna V.,Gawade, Rupesh L.,Kotmale, Amol S.,Prabhakaran, Panchami,Gonnade, Rajesh G.,Puranik, Vedavadi G.,Rajamohanan, Pattuparambil R.,Sanjayan, Gangadhar J.
supporting information, p. 8348 - 8356 (2013/12/04)
Although known for their inferiority as hydrogen-bonding acceptors when compared to amides, esters are often found at the C-terminus of peptides and synthetic oligomers (foldamers), presumably due to the synthetic readiness with which they are obtained using protected peptide coupling, deploying amino acid esters at the C-terminus. When the H-bonding interactions deviate from regularity at the termini, peptide chains tend to "fray apart". However, the individual contributions of C-terminal esters in causing peptide chain end-fraying goes often unnoticed, particularly due to diverse competing effects emanating from large peptide chains. Herein, we describe a striking case of a comparison of the individual contributions of C-terminal ester vs. amide carbonyl as a H-bonding acceptor in the folding of a peptide. A simple two-residue peptide fold has been used as a testing case to demonstrate that amide carbonyl is far superior to ester carbonyl in promoting peptide folding, alienating end-fraying. This finding would have a bearing on the fundamental understanding of the individual contributions of stabilizing/destabilizing non-covalent interactions in peptide folding.
