1552-91-6Relevant academic research and scientific papers
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
, (2018)
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.
HETEROCYCLIC COMPOUNDS AS INHIBITORS OF HPK1
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, (2021/01/29)
This disclosure relates to heterocyclics as inhibitors of HPK1, in particular relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising said compound that useful for treatment of HPK1 mediated diseases and conditions such as cancer. (I)
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
, 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).
Transition-metal-free C-P bond formation via decarboxylative phosphorylation of cinnamic acids with P(O)H compounds
Liu, Lixin,Zhou, Dan,Dong, Jianyu,Zhou, Yongbo,Yin, Shuang-Feng,Han, Li-Biao
, p. 4190 - 4196 (2018/04/14)
A novel, transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds has been developed via radical-promoted decarboxylation under mild conditions. This method provides simple, efficient, and versatile access to valuable (E)-alkenylphosphine oxides in satisfactory yields with a wide variety of substrates.
USE OF SUBSTITUTE OXO TETRAHYDROQUINOLINE SULFONAMIDES OR SALTS THEREOF FOR RAISING STRESS TOLERANCE OF PLANTS
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, (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.
Pd-Catalyzed α-Selective C-H Functionalization of Olefins: En Route to 4-Imino-β-Lactams
Kong, Wei-Jun,Liu, Yue-Jin,Xu, Hui,Chen, Yan-Qiao,Dai, Hui-Xiong,Yu, Jin-Quan
, p. 2146 - 2149 (2016/03/05)
Pd-catalyzed α-olefinic C-H activation of simple α,β-unsaturated olefins has been developed. 4-imino-β-lactam derivatives were readily synthesized via activation of α-olefinic C-H bonds with excellent cis stereoselectivity. A wide range of heterocycles at the β-position are compatible with this reaction. The product of 4-imino-β-lactam derivatives can be readily converted to 2-aminoquinoline which exists extensively in pharmaceutical drugs and natural products.
SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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, (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.
Cobalt- and Nickel-Catalyzed Carboxylation of Alkenyl and Sterically Hindered Aryl Triflates Utilizing CO2
Nogi, Keisuke,Fujihara, Tetsuaki,Terao, Jun,Tsuji, Yasushi
, p. 11618 - 11623 (2015/12/01)
A highly efficient cobalt-catalyzed reductive carboxylation reaction of alkenyl trifluoromethanesulfonates (triflates) has been developed. By employing Mn powder as a reducing reagent under 1 atm pressure of CO2 at room temperature, diverse alkenyl triflates can be converted to the corresponding α,β-unsaturated carboxylic acids. Moreover, the carboxylation of sterically hindered aryl triflates proceeds smoothly in the presence of a nickel or cobalt catalyst.
HETEROCYCLIC DERIVATIVE HAVING INHIBITORY ACTIVITY ON TYPE-I 11 -HYDROXYSTEROID DEHYDROGENASE
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Page/Page column 173, (2010/08/07)
Disclosed is a compound which is useful as an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula: its pharmaceutically acceptable salt, or a solvate thereof, wherein X is O or S, a broken line and a wavy line represent the presence or the absence of a bond, (i) when a broken line represents the presence of a bond, a wavy line represents the absence of a bond, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, (ii) when a broken line represents the absence of a bond, a wavy line represents the presence of a bond, R1 and R4 are each independently hydrogen, halogen or the like, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, and R5 and R6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like.
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.
