- Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline-Based Lead Structure
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New oxotetrahydroquinolinyl- and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in-depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo-tetrahydro-quinolines and amino oxo-indolines as essential intermediates gave access to the envisaged oxo-tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo-tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro-cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro-oxindolinyl and oxo-tetrahydroquinolinyl sulfonamides carrying optimized N-substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in-vivo (canola and wheat as broad-acre crops).
- Baltz, Rachel,Bojack, Guido,Dittgen, Jan,Fischer, Christian,Frackenpohl, Jens,Freigang, J?rg,Getachew, Rahel,Grill, Erwin,Helmke, Hendrik,Hohmann, Sabine,Lange, Gudrun,Lehr, Stefan,Porée, Fabien,Schmidt, Jana,Schmutzler, Dirk,Yang, Zhenyu
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- Aminoluciferins extend firefly luciferase bioluminescence into the near-infrared and can be preferred substrates over d-luciferin
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Firefly luciferase adenylates and oxidizes D-luciferin to chemically generate visible light and is widely used for biological assays and imaging. Here we show that both luciferase and luciferin can be reengineered to extend the scope of this light-emitting reaction. D-Luciferin can be replaced by synthetic luciferin analogues that increase near-infrared photon flux >10-fold over that of D-luciferin in live luciferase-expressing cells. Firefly luciferase can be mutated to accept and utilize rigid aminoluciferins with high activity in both live and lysed cells yet exhibit 10 000-fold selectivity over the natural luciferase substrate. These new luciferin analogues thus pave the way to an extended family of bioluminescent reporters.
- Mofford, David M.,Reddy, Gadarla Randheer,Miller, Stephen C.
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, lI-P, or III. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH).
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- USE OF SUBSTITUTE OXO TETRAHYDROQUINOLINE SULFONAMIDES OR SALTS THEREOF FOR RAISING STRESS TOLERANCE OF PLANTS
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The invention relates to the use of substituted oxotetrahydroquinolinylsulfonamides or salts thereof where the radicals in the general formula (I) correspond to the definitions given in the description, for enhancing stress tolerance in plants to abiotic stress, and/or for increasing plant yield.
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- COMPOUNDS ACTIVE TOWARDS BROMODOMAINS
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Disclosed are compounds towards bromodomains, pharmaceutical compositions containing the compounds and use of the compounds in therapy.
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