- TARGETED PROTEIN DEGRADATION OF PARP14 FOR USE IN THERAPY
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The present invention relates to quinazolinones and related compounds which degrade PARP14 and are useful, for example, in the treatment of cancer and inflammatory diseases.
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Page/Page column 73-74
(2021/01/22)
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- NOVEL 5-AMINO-2-THIOIMIDAZOLE COMPOUNDS AND THEIR USE
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The present invention is directed to novel compounds of formula (I) pharmaceutically acceptable salts or solvates thereof, and their use.
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Page/Page column 74; 75
(2017/04/01)
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- Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance
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The role of the G-protein-coupled bile acid receptor TGR5 in various organs, tissues, and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability. In this article, we describe their synthesis, characterization, and biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue, has low effect on gallbladder volume, and improves glucose homeostasis in a preclinical murine model of diet-induced obesity and insulin resistance, making the proof of concept of the potential of topical intestinal TGR5 agonists as therapeutic agents in type-2 diabetes.
- Lasalle, Manuel,Hoguet, Vanessa,Hennuyer, Nathalie,Leroux, Florence,Piveteau, Catherine,Belloy, Lo?c,Lestavel, Sophie,Vallez, Emmanuelle,Dorchies, Emilie,Duplan, Isabelle,Sevin, Emmanuel,Culot, Maxime,Gosselet, Fabien,Boulahjar, Rajaa,Herledan, Adrien,Staels, Bart,Deprez, Benoit,Tailleux, Anne,Charton, Julie
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p. 4185 - 4211
(2017/06/05)
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- IMIDAZOL- OR 1,2,4-TRIAZOL-DERIVATIVES AND THEIR USE
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The present invention is directed to novel compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.
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Page/Page column 45
(2016/01/01)
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- Synthesis and mesomorphic properties of two series of laterally fluorinated symmetric ester liquid crystals
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Two series of symmetric ester liquid crystals (nAFBHQ and nADFBHQ) with lateral fluorine atoms have been synthesized. Their chemical structures were measured by FTIR, 1H NMR, and elemental analysis (EA). Their mesomorphic properties were investigated by d
- Wei, Qiang,Yuan, Xiaotao,Zhang, Lipei,Wang, Liping,Yang, Huai,Wang, Yangbin
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experimental part
p. 52 - 60
(2010/03/25)
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- The regioexhaustive functionalization of difluorophenols and trifluorophenols through organometallic intermediates
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2,4-Difluorophenol, 2,5-difluorophenol, 2,3-difluorophenol, 3,5-difluorophenol, 3,4-difluorophenol, 2,4,5-trifluorophenol and 2,3,4-trifluorophenol were converted into all 18 possible di- or trifluorinated hydroxybenzoic acids (1a-c, 4a-c, 9a-c, 12a,b, 14a-c, 17a,b, 18a,b), all of them new compounds. The phenolic hydrogen atom was replaced by a methoxymethyl or, less frequently, by a triisopropylsilyl group, which exerted an ortho activating or ortho shielding effect, respectively. Sites flanked by two electronegative substituents (fluorine, alkoxy) were deprotonated with particular ease. They had to be silenced by the reversible attachment of a metalation-blocking trimethylsilyl group or of a metalation-deflecting chlorine atom if the metal was to be introduced elsewhere. In all cases but one, the stage was thus set for an intramolecular competition between metalation at an oxygen-adjacent or a fluorine-adjacent site. It proved indeed possible to secure the desired regioflexibility in either way by relying on an appropriate substrate-reagent matching. This demonstrates once more the potential of the organometallic approach to diversity-oriented synthesis.
- Marzi, Elena,Gorecka, Joanna,Schlosser, Manfred
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p. 1609 - 1618
(2007/10/03)
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- Regio-selective hydroxysubstitution of fluorobenzoic acid derivatives: Facile synthesis of fluorosalicylic acid derivatives
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Ortho-substituted fluorine in 2,4-difluorobenzoic acid was found to be regio-selectively replaced to hydroxide by solid sodium hydroxide in 1,3-dimethyl-2-imidazolidinone, to afford 4-fluoro-2-hydroxybenzoic acid in high yield. Several multi-fluoro-substi
- Umezu, Kazuto,Tabuchi, Fumiya,Kimura, Yoshikazu
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