- Painting argyrins blue: Negishi cross-coupling for synthesis of deep-blue tryptophan analogue β-(1-azulenyl)-L alanine and its incorporation into argyrin C
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The argyrins are a family of non-ribosomal peptides that exhibits different biological activities through only small structural changes. Ideally, a biologically active molecule can be tracked and observed in a variety of biological and clinical settings in a non-invasive manner. As a step towards this goal, we report here a chemical synthesis of unnatural deep blue amino acid β-(1-azulenyl)-L alanine with different fluorescence and photophysical properties, which allows a spectral separation from the native tryptophan signal. This might be especially useful for cell localization studies and visualizing the targeted proteins. In particular, the synthesis of β-(1-azulenyl)-L alanine was achieved through a Negishi coupling which proved to be a powerful tool for the synthesis of unnatural tryptophan analogs. Upon β-(1-azulenyl)-L alanine incorporation into argyrin C, deep blue octapeptide variant was spectrally and structurally characterized.
- Stempel, Erik,Kaml, Robert Franz-Xaver,Budisa, Nediljko,Kalesse, Markus
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- A novel series of parenteral cephalosporins exhibiting potent activities against both Pseudomonas aeruginosa and other Gram-negative pathogens. Part 2: Synthesis and structure-activity relationships
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A novel series of 7β-[2-(2-amino-5-chloro-thiazol-4-yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]cephalosporins bearing various pyridinium groups at the C-3′ position were synthesized and their in vitro antibacterial activities against Gram-negative patho
- Yamawaki, Kenji,Nomura, Takashi,Yasukata, Tatsuro,Tanimoto, Norihiko,Uotani, Koichi,Miwa, Hideaki,Yamano, Yoshinori,Takeda, Kei,Nishitani, Yasuhiro
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- Blue fluorescent amino acids as in vivo building blocks for proteins
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In vivo expression of colored proteins without post-translational modification or chemical functionalization is highly desired for protein studies and cell biology. Cell-permeable tryptophan analogues, such as azatryptophans, have proved to be almost ideal isosteric substitutes for natural tryptophan in cellular proteins. Their unique spectral features, such as markedly redshifted fluorescence, are transmitted into protein structures upon incorporation. Among the azaindoles under study (2-, 4-, 5-, 6-, and 7-azaindole) 4-azaindole has exhibited the largest Stokes shift (~130 nm) in steady-state fluorescence measurements. It is also highly biocompatible and as 4-azatryptophan it can be translated into target protein sequences. However, its quantum yield and fluorescence intensity are still significantly lower when compared with natural indole/tryptophan. Since azatryptophans are hydrophilic, their presence in the hydrophobic core of proteins could be harmful. In order to overcome these limitations we have performed nitrogen methylation of azaindoles and generated mono- and dimethylated azaindoles. Some of these methyl derivatives retain the pronounced red shift present in the parent 4-azaindole, but with much higher fluorescence intensity (reaching the level of indole/tryptophan). Therefore, the blue fluorescence of azaindole-containing proteins could be further enhanced by the use of methylated analogues. Further substitution of any azaindole ring with either endo- or exocyclic nitrogen will not yield a spectral fluorescence maximum shift beyond 450 nm under steady-state conditions in the physiological milieu. However, green fluorescence is a special feature of tautomeric species of azaindoles in various nonaqueous solvents. Thus, the design or evolution of the protein interior combined with the incorporation of these azaindoles might lead to the generation of specific chromophore microenvironments that facilitate tautomeric or protonated/deprotoned states associated with green fluorescence.
- Merkel, Lars,Hoesl, Michael G.,Albrecht, Marcel,Schmidt, Andreas,Budisa, Nediljko
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- NOVEL SUBSTITUTED TETRAHYDROQUINOLIN COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS
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Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof (I). Also disclosed herein are uses of the compounds disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
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Page/Page column 167
(2019/05/22)
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- CANCER TREATMENTS TARGETING CANCER STEM CELLS
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Disclosed are compounds, methods, compositions, and kits that allow for treating cancer by, e.g., targeting cancer stem cells. In some embodiments, the cancer is colorectal cancer, gastric cancer, gastrointestinal stromal tumor, ovarian cancer, lung cancer, breast cancer, pancreatic cancer, prostate cancer, testicular cancer, or lymphoma. In some embodiments, the cancer is liver cancer, endometrial cancer, leukemia, or multiple myeloma. The compounds utilized in the disclosure are of Formula (0), (O'), and (I):
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Paragraph 0331; 0543; 0554-0556
(2019/11/19)
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- BICYCLIC DIAMINES AS JANUS KINASE INHIBITORS
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The instant invention provides compounds of formula I which are Jak inhibitors, and as such are useful for the treatment of Jak-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
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Paragraph 0096
(2019/01/04)
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- ISOQUINOLINESULFONYL DERIVATIVE AS RHO KINASE INHIBITOR
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The present invention discloses a class of isoquinolinesulfonyl derivatives as RHO kinase inhibitors, and pharmaceutical compositions thereof, and relates to pharmaceutically acceptable uses thereof. Specifically, the present invention relates to a compound as represented by formula (I), or a pharmaceutically acceptable salt thereof.
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Paragraph 0114-0116
(2017/06/12)
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- GPR 119 MODULATORS
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Compounds of Formula (I) that modulate the activity of the G -protein-coupled receptor GPFM 19 and their uses in the treatment of diseases linked to the modulation of the G-protein-coupled receptor GPR119 in animals are described herein.
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Page/Page column 58
(2010/11/18)
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- Palladium-catalysed tandem alkenyl- and aryl-C-N bond formation: a cascade N-annulation route to 1-functionalised 7-azaindoles
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A series of 3-(2-haloalkenyl)-2-pyridyl-halides undergo consecutive palladium-catalysed inter- and intramolecular amination reactions to deliver a series of 1-functionalised 7-azaindoles. Anilines and amines can be readily employed as the N-nucleophile an
- Hodgkinson, Roy C.,Schulz, Jurgen,Willis, Michael C.
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experimental part
p. 8940 - 8949
(2009/12/08)
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