- Novel camptothecin derivative, and preparation method and application thereof
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The invention relates to a novel camptothecin derivative and application thereof, a tumor cell growth inhibitor, a ternary complex, and a method for improving the solubility of the camptothecin derivative. The camptothecin derivative is formed by modifying a substance represented by formula I through glycosylated triazole in the position R3. In a structural formula represented by the formula I, R1represents H, alkyl of C1-10, deuterated alkyl of the C1-10, or halogenated alkyl of the C1-10; R2 represents H, CH2N(CH3)2 or CH2N(CD3)2; R4 represents H, and X represents N, O or S; L represents polypeptide, C1-20 linear alkyl or a derivative thereof, a C1-20 linear or branched acyl derivative, or C2-100 ethylene glycol or a derivative thereof. The camptothecin derivative has high solubility, prepared anticancer drugs have the advantages of wide anticancer spectrum and high safety, and the in-vivo anticancer activity is superior to that of irinotecan hydrochloride.
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Paragraph 0152-0153; 0156
(2020/03/12)
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- Exploring the Implication of DDX3X in DENV Infection: Discovery of the First-in-Class DDX3X Fluorescent Inhibitor
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In the absence of effective drugs or vaccines for the treatment of the five Dengue Virus serotypes, the search for novel antiviral drugs is of primary importance for the scientific community. In this context, drug repurposing represents the most used strategy; however, the study of host targets is now attracting attention since it allows identification of broad-spectrum drugs endowed with high genetic barrier. In the last ten years our research group identified several small molecules DDX3X inhibitors and proved their efficacy against different viruses including novel emerging ones. Herein, starting from a screening of our compounds, we designed and synthesized novel derivatives with potent activity and high selectivity. Finally, we synthesized a fluorescent inhibitor that allowed us to study DDX3X cellular localization during DENV infection in vitro. Immunofluorescence analysis showed that our inhibitor colocalized with DDX3X, promoting the reduction of infected cells and recovering the number of viable cells.
- Boccuto, Adele,Botta, Maurizio,Brai, Annalaura,Dreassi, Elena,Garbelli, Anna,Maga, Giovanni,Marchi, Serena,Monti, Martina,Montomoli, Emanuele,Nola, Emanuele Maria,Pollutri, Alessandro,Riva, Valentina,Saladini, Francesco,Trivisani, Claudia Immacolata,Trombetta, Claudia Maria,Vicenti, Ilaria,Zazzi, Maurizio
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supporting information
(2020/04/20)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 2386; 2387
(2019/07/10)
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- BETA-LACTAMASE INHIBITORS
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Described herein are compounds and compositions that modulate the activity of beta -lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.
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Paragraph 0390
(2017/04/08)
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- Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights to Realize the Enantioselective Synthesis of Piperazines
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An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η6-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated.
- Lau, Ying Yin,Zhai, Huimin,Schafer, Laurel L.
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p. 8696 - 8709
(2016/10/14)
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- Ruthenium-catalyzed hydroamination of aminoallenes: An approach to vinyl substituted heterocycles
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Heterosubstituted aminoallenes underwent smooth ruthenium-catalyzed intramolecular exo-hydroamination reactions yielding the corresponding five-, six-, or seven-membered 1,3-diaza- or 1,3-oxaza-heterocyclic structures. This procedure is a valuable and less expensive alternative to the already known transition metal-catalyzed hydroamination reactions of aminoallenes.
- Broggini, Gianluigi,Poli, Giovanni,Beccalli, Egle M.,Brusa, Filippo,Gazzola, Silvia,Oble, Julie
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supporting information
p. 677 - 682
(2015/03/18)
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- Synthesis and evaluation of a photoactive probe with a multivalent carbohydrate for capturing carbohydrate-lectin interactions
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Lectins are ubiquitous carbohydrate-binding proteins of nonimmune origin that are characterized by their specific recognition of defined monosaccharide or oligosaccharide structures. However, the use of carbohydrates to study lectin has been restricted by the weak binding affinity and noncovalent character of the interaction between carbohydrates and lectin. In this report, we designed and synthesized a multifunctional photoaffinity reagent composed of a trialkyne chain, a masked latent amine group, and a photoreactive 3-trifluoromethyl-3- phenyl-diazirine group in high overall yield. Two well-defined chemistries, Huisgen-Sharpless click chemistry and amide bond coupling, were the key steps for installing the multivalent character and tag in our designed photoaffinity probe. The photolabeling results demonstrated that the designed probe selectively labeled the target lectin, RCA120 (Ricinus communis Agglutinin), in an E. coli lysate and an asialoglycoprotein receptor (ASGP-R) on intact HepG2 cell membranes. Moreover, the probe also enabled the detection of weak protein-protein interactions between RCA120 and ovalbumin (OVA).
- Chang, Tsung-Che,Lai, Chian-Hui,Chien, Chih-Wei,Liang, Chien-Fu,Adak, Avijit Kumar,Chuang, Yung-Jen,Chen, Yu-Ju,Lin, Chun-Cheng
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p. 1895 - 1906
(2014/01/06)
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- COMPOUNDS FOR THE INHIBITION OF CELLULAR PROLIFERATION
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Compositions and methods for inhibiting translation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, (4) disorders associated with viral infections, and/or (5) non-proliferative metabolic disorders such as type II diabetes where inhibition of translation initiation is beneficial using the compounds disclosed herein.
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Page/Page column 73-75
(2012/02/01)
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- PEPTIDE NUCLEIC ACID DERIVATIVES WITH GOOD CELL PENETRATION AND STRONG AFFINITY FOR NUCLEIC ACID
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The present invention provides a novel class of peptide nucleic acid derivatives, which show good cell penetration and strong binding affinity for nucleic acid.
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- PEPTIDE NUCLEIC ACID DERIVATIVES WITH GOOD CELL PENETRATION AND STRONG AFFINITY FOR NUCLEIC ACID
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The present invention provides a novel class of peptide nucleic acid derivatives, which show good cell penetration and strong binding affinity for nucleic acid.
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Page/Page column 30
(2009/10/22)
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- MACROLONE COMPOUNDS
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A compound of formula (I) compositions comprising same, processes for their preparation and use of said compounds, particularly in the treatment of microbial infections.
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Page/Page column 42
(2008/06/13)
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- Ether linked macrolides useful for the treatment of microbial infections
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The present invention relates to 14- or 15-membered macrolides substituted at the 4″ position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or top
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Page/Page column 28
(2008/06/13)
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- MACROLONES - AMINO SUBSTITUTED QUINOLONES
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Compounds of formula (I) or pharmaceutically acceptable derivatives thereof having antimicrobial activity are disclosed, as are processes for their preparation, compositions containing them and their use in medicine.
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Page/Page column 67
(2010/11/30)
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- MACROLONE COMPOUNDS
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A compound of formula (I) For use as antibacterial agents, compositions containing same, processes for their preparation and their use in therapy.
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Page/Page column 50
(2010/11/30)
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- 4" AMINO LINKED MACROLIDES USEFUL FOR THE TREATMENT OF MICROBIAL INFECTIONS
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The present invention relates to 15-membered macrolides substituted at the 4" position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical mi
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Page/Page column 43
(2008/06/13)
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- ESTER LINKED MACROLIDES USEFUL FOR THE TREATMENT OF MICROBIAL INFECTIONS
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The present invention relates to 14- or 15-membered macrolides substituted at the 4” position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or top
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Page/Page column 49
(2008/06/13)
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- CARBAMATE LINKED MACROLIDES USEFUL FOR THE TREATMENT OF MICROBIAL INFECTIONS
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The present invention relates to 14- or 15-membered macrolides substituted at the 4" position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical microbial infections in a human or animal body.
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Page/Page column 56-57
(2010/02/14)
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- Ether substituted imidazopyridines
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Imidazopyridine compounds that contain an ether or thioether functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases. Methods of preparing the compounds and intermediates useful in the preparation of the compounds are also disclosed.
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