15028-39-4Relevant academic research and scientific papers
Synthesis and Penicillin-binding Protein Inhibitory Assessment of Dipeptidic 4-Phenyl-β-lactams from α-Amino Acid-derived Imines
Decuyper, Lena,Juki?, Marko,Sosi?, Izidor,Amoroso, Ana Maria,Verlaine, Olivier,Joris, Bernard,Gobec, Stanislav,D'hooghe, Matthias
supporting information, p. 51 - 55 (2019/11/28)
Monocyclic β-lactams revive the research field on antibiotics, which are threatened by the emergence of resistant bacteria. A six-step synthetic route was developed, providing easy access to new 3-amino-1-carboxymethyl-4-phenyl-β-lactams, of which the penicillin-binding protein (PBP) inhibitory potency was demonstrated biochemically.
Histone deacetylase 6 inhibitor and preparation method and application thereof
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Paragraph 0067-0070, (2020/11/12)
The invention discloses a histone deacetylase 6 inhibitor and a preparation method and application thereof. The histone deacetylase 6 inhibitor has a structure as shown in the following general formula (I). The invention further provides a preparation method of the compound and application of the compound in preparation of drugs for preventing or treating diseases related to HDAC6 activity or abnormal expression.
((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies
Liu, Sha,Jing, Li,Yu, Zhu-Jun,Wu, Chengyong,Zheng, Yongxiang,Zhang, En,Chen, Qiang,Yu, Yamei,Guo, Li,Wu, Yong,Li, Guo-Bo
, p. 649 - 660 (2018/02/10)
The emergence and global spread of metallo-β-lactamase (MBL) mediated resistance to almost all β-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis.
PYRIMIDONE DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE
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Page/Page column 217; 218, (2017/10/11)
The present invention relates to a compound having the general formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease, in particular influenza.
Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling
Kim, Byoungmoo,Chinn, Alex J.,Fandrick, Daniel R.,Senanayake, Chris H.,Singer, Robert A.,Miller, Scott J.
supporting information, p. 7939 - 7945 (2016/07/07)
We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate.
HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Paragraph 00730, (2016/05/02)
Disclosed are heteroaryl derivatives, pharmaceutical composition and uses in the manufacture of a medicine for treating respiratory diseases, especially for chronic obstructive pulmonary disease (COPD).
Phenylalanine and Phenylglycine Analogues as Arginine Mimetics in Dengue Protease Inhibitors
Weigel, Lena F.,Nitsche, Christoph,Graf, Dominik,Bartenschlager, Ralf,Klein, Christian D.
, p. 7719 - 7733 (2015/10/20)
Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine-mimicking groups with modulated basicity. The most promising compounds were (4-amidino)-l-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease. The type and position of the substituents on the phenylglycine and phenylalanine side chains has a significant effect on the inhibitory activity against dengue virus protease and selectivity against other proteases. In addition, the non-natural, basic amino acids described here may have relevance for the development of other peptidic and peptidomimetic drugs such as inhibitors of the blood clotting cascade.
Efficient asymmetric addition of diethylzinc to aldehydes using C 2-novel chiral pyridine β-amino alcohols as chiral ligands
Zhang, Weijie,Tang, Ruiren,Yu, Huirong,Gao, Shu
, p. 545 - 551 (2014/07/07)
A series of novel C2-symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1H NMR, 13C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2R)-2,2-((pyridine-2,6-diylbis(methylene)) bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2R)-2,2-((1,3-phenylenebis(methylene)) bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright
Thiourea-catalyzed enantioselective fluorination of β-keto esters
Xu, Junxing,Hu, Yulai,Huang, Danfeng,Wang, Ke-Hu,Xu, Changming,Niu, Teng
supporting information; experimental part, p. 515 - 526 (2012/04/04)
Bifunctional chiral thioureas have been successfully used as organocatalysts in enantioselective fluorinations of β-keto esters. The corresponding products could be obtained with good to excellent enantioselectivity in high yields by using N-fluorobisbenzenesulphonimide (NFSI) as fluorination reagent. Copyright
Asymmetric strecker synthesis of α-arylglycines
Perez-Fuertes, Yolanda,Taylor, James E.,Tickell, David A.,Mahon, Mary F.,Bull, Steven D.,James, Tony D.
, p. 6038 - 6047 (2011/10/08)
A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4- methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.
