1903-27-1Relevant articles and documents
Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline-Based Lead Structure
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
supporting information, p. 3442 - 3457 (2021/06/25)
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).
Synthesis of novel shikonin derivatives and pharmacological effects of cyclopropylacetylshikonin on melanoma cells
Durchschein, Christin,Bauer, Rudolf,Kretschmer, Nadine,Hufner, Antje,Rinner, Beate,Stallinger, Alexander,Deutsch, Alexander,Lohberger, Birgit
supporting information, (2018/11/23)
Despite much research in the last centuries, treatment of malignant melanoma is still challenging because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Therefore, the discovery of novel drug leads is an important goal. In a previous study, we have isolated several shikonin derivatives from the roots of Onosma paniculata Bureau & Franchet (Boraginaceae) which evolved as promising anticancer candidates. β,β-Dimethylacrylshikonin (1) was the most cytotoxic derivative and exhibited strong tumor growth inhibitory activity, in particular, towards melanoma cells. In this study, we synthesized eighteen novel shikonin derivatives in order to obtain compounds which exhibit a higher cytotoxicity than 1. We investigated their cytotoxic potential against various melanoma cell lines and juvenile skin fibroblasts. The most active compound was (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclopropylacetate (cyclopropylacetylshikonin) (6). It revealed significant stronger tumor growth inhibitory activity towards two melanoma cell lines derived from metastatic lesions (WM164 and MUG-Mel2). Further investigations have shown that 6 induced apoptosis caspase-dependently, increased the protein levels of cleaved PARP, and led to double-stranded DNA breaks as shown by phosphorylation of H2AX. Cell membrane damage and cell cycle arrest were not observed.
USE OF SUBSTITUTE OXO TETRAHYDROQUINOLINE SULFONAMIDES OR SALTS THEREOF FOR RAISING STRESS TOLERANCE OF PLANTS
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Paragraph 0199, (2017/02/28)
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.
Ni-Catalyzed Carboxylation of Unactivated Alkyl Chlorides with CO2
B?rjesson, Marino,Moragas, Toni,Martin, Ruben
supporting information, p. 7504 - 7507 (2016/07/06)
A catalytic carboxylation of unactivated primary, secondary, and tertiary alkyl chlorides with CO2 at atmospheric pressure is described. This protocol represents the first intermolecular cross-electrophile coupling of unactivated alkyl chlorides, thus leading to new knowledge in the cross-coupling arena.
SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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Paragraph 000148, (2015/03/13)
The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.
Ni-Catalyzed Divergent Cyclization/Carboxylation of Unactivated Primary and Secondary Alkyl Halides with CO2
Wang, Xueqiang,Liu, Yu,Martin, Ruben
supporting information, p. 6476 - 6479 (2015/06/08)
A user-friendly Ni-catalyzed reductive cyclization/carboxylation of unactivated alkyl halides with CO2 is described. The protocol operates under mild conditions with an excellent chemoselectivity profile and a divergent syn/anti selectivity pat
Fluoro-olefins as peptidomimetic inhibitors of dipeptidyl peptidases
Van Der Veken, Pieter,Senten, Kristel,Kertèsz, István,De Meester, Ingrid,Lambeir, Anne-Marie,Maes, Marie-Berthe,Scharpé, Simon,Haemers, Achiel,Augustyns, Koen
, p. 1768 - 1780 (2007/10/03)
The feasibility of the fluoro-olefin function as a peptidomimetic group in inhibitors for dipeptidyl peptidase IV and II (DPP IV and DPP II) is investigated by evaluation of N-substituted Gly-Ψ[CF=C]pyrrolidines, Gly-Ψ[CF=C]piperidines, and Gly-Ψ[CF=C](2-cyano)pyrrolidines. Of this later class, the (Z)- and (E)-fluoro-olefin analogues were prepared and chemical stability in comparison with the parent amide was checked. Most of these compounds exhibited a strong binding preference toward DPP II with IC 50 values in the low micromolar range, while only low DPP IV inhibitory potential is seen.
Reaction of N-acetylimidazole with enamines
Cook, Gilbert,Waddle, Julie L.
, p. 6923 - 6925 (2007/10/03)
N-Acetylimidazole is a commonly used acylating reagent. When it is allowed to react with several typical enamines, amides are produced rather than the expected acylated enamines.
Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction
Friese, Anke,Hell-Momeni, Katja,Zündorf, Ilse,Winckler, Thomas,Dingermann, Theodor,Dannhardt, Gerd
, p. 1535 - 1542 (2007/10/03)
The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.
Structure-activity relationships of unsaturated analogues of valproic acid
Palaty,Abbott
, p. 3398 - 3406 (2007/10/02)
The principal metabolite of valproic acid (VPA), 2-ene VPA, appears to share most of VPA's pharmacological and therapeutic properties while lacking its hepatotoxicity and teratogenicity, thus making it a useful lead compound for the development of safer antiepileptic drugs. Analogues of 2-ene VPA were evaluated for anticonvulsant activity in mice using the subcutaneous pentylenetetrazole test. Cyclooctylideneacetic acid exhibited a potency markedly exceeding that of VPA itself with only modest levels of sedation. Potency, as either ED50 or brain concentration, was highly correlated (r > 0.85) with volume and lipophilicity rather than with one of the shape parameters calculated by molecular modeling techniques, arguing against the existence of a specific receptor site. Instead, a role for the plasma membrane in mediating the anticonvulsant effect is suggested.
