- SUBSTITUTED BICYCLIC COMPOUNDS AS MODULATORS OF THE ARYL HYDROCARBON RECEPTOR (AHR)
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The present invention relates to bicyclic compounds which can act as aryl hydrocarbon receptor (AhR) modulators and, in particular, as AhR antagonists. The invention further relates to the use of the compounds for the treatment and/or prophylaxis of diseases and/or conditions through binding of said aryl hydrocarbon receptor by said compounds. A-B-L-C (I)
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Page/Page column 73
(2020/02/16)
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- Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study
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Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, which makes the modulation of hSirt2 activity a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently been discovered by us as highly potent and isotype-selective hSirt2 inhibitors. Here, we present a well-defined structure-activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the hSirt2 targeted tubulin caused by our improved lead structure.
- Schiedel, Matthias,Rumpf, Tobias,Karaman, Berin,Lehotzky, Attila,Oláh, Judit,Gerhardt, Stefan,Ovádi, Judit,Sippl, Wolfgang,Einsle, Oliver,Jung, Manfred
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p. 1599 - 1612
(2016/03/05)
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- QUINOLINE DERIVATIVES
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The invention concerns quinoline derivatives of Formula I or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 49
(2009/04/24)
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- QUINOLINE DERIVATIVES
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The invention concerns quinoline derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 163
(2008/06/13)
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- QUINOLINE DERIVATIVES FOR TREATING CANCER
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The invention concerns quinoline derivatives of Formula (I) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 112
(2008/06/13)
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- NAPHTHYRIDINE DERIVATIVES AS ANTI-CANCER AGENTS
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The invention concerns naphthyridine derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 110-111
(2010/11/28)
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- Reaction of 2-Aminothiazoles with Reagents containing a C-Halogen and a C=O Electrophilic Centre
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Seven reagents of different types having in common a C-Hal and a C=O electrophilic centre have been used in a study of their reactions with 2-aminothiazoles.Three reagents, CHBrAc2 and ROCHBrCO2Et (R = Me, Ph), gave imidazothiazoles, thus providing useful routes to the 5-acetyl and 5-ethoxycarbonyl derivatives.Unexpectedly, the solvent (acetone) was involved in the reaction of the fourth reagent, CHBr(CO2Et)2, with 2-aminothiazole which led to 5,5-di(ethoxycarbonyl)-6,6-dimethyl-5,6-dihydroimidazothiazole (yield 81percent).With the last three reagents (AcCHBrNO2, BzCHBrCN and ICH2CO2C6H4NO2-p) the outcome was simpler, viz., the formation of 2-amidothiazoles.It is proposed that electrophilic attack by the endo-N of the 2-aminothiazole is the first step in all cases.This occurs at the C-Hal centre of the first four reagents and is followed by cyclisation to the exo-N.In the last three electrophiles the presence of the groups well suited to leaving as stabilised anions favours addition to the C=O group; the intermediates so formed subsequently isomerise to the more stable exo-N substituted products.
- Compton, Victoria J.,Meakins, G. Denis,Raybould, Amanda J.
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p. 2029 - 2032
(2007/10/02)
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