- Synthesis, cytotoxicity and structure-activity relationship of indolizinoquinolinedione derivatives as DNA topoisomerase IB catalytic inhibitors
-
Our previous studies reveal that indolizinoquinolinedione scaffold is a base to develop novel DNA topoisomerase IB (TOP1) catalytic inhibitors. In this work, twenty-three novel indolizinoquinolinedione derivatives were synthesized. TOP1-mediated relaxation, nicking and unwinding assays revealed that three fluorinated derivatives 26, 28 and 29, and one N,N-trans derivative 46 act as TOP1 catalytic inhibitors with higher TOP1 inhibition (++++) than camptothecin (+++) and without TOP1-mediated unwinding effect. MTT assay against five human cancer cell lines indicated that the highest cytotoxicity is 20 for CCRF-CEM cells, 25 for A549 and DU-145 cells, 26 for HCT116 cells, and 33 for Huh7 cells with GI50 values at nanomolar range. The drug-resistant cell assay indicated that compound 26 may mainly act to TOP1 in cells and are less of Pgp substrates. Flow cytometric analysis showed that compounds 26, 28 and 29 can obviously induce apoptosis of HCT116 cells. Moreover, the structure-activity relationship (SAR) of indolizinoquinolinedione derivatives was analyzed.
- Yu, Qian,Yang, Hui,Zhu, Teng-Wei,Yu, Le-Mao,Chen, Jian-Wen,Gu, Lian-Quan,Huang, Zhi-Shu,An, Lin-Kun
-
-
Read Online
- Method of preparing Quinoline-5,8-dione derivatives for TGase 2 inhibitor
-
I Is -5,8- of the quinoline, dione derivative compound. of Formula I, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein the compound of Formula, TGase 2 has, inhibitory effects TGase 2, and thus the pharmaceutical composition may be useful for preventing or treating disorders or diseases mediated by TGase 2 or inhibiting. (by machine translation)
- -
-
Paragraph 0549-0552
(2020/04/28)
-
- Tricycloisoxazole compound and preparation and application methods thereof
-
The invention discloses a tricycloisoxazole compound and a medically acceptable salt thereof. The structure of the tricycloisoxazole compound is shown as the formula I, wherein A is thienyl, furyl, phenyl and pyridyl; R1 is hydrogen, halogen, amido, substituted amido, nitro, acylamino, substituted acylamino, cyan, low alkyl and alkoxy; R2 is alkyl, alkoxy, alkoxy alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl; R3 is carbon or hydroxyl; X is carbon atom or oxygen atom, and when being carbon atom, is connected with the substituted group R3, which is carbonyl or carboxyl. The invention also provides preparation and application methods of the tricycloisoxazole compound, namely, the tricycloisoxazole compound can serve as an antifungal small-molecule inhibitor. In vitro antifungal activity experiment results show that most of the tricycloisoxazole compound shown as the formula I achieves good antifungal activity, especially significantly higher antifungal activity on Cryptococcus neoformans compared with a positive fungicide of fluconazole, thereby being applicable to preparing antifungal drugs.
- -
-
Paragraph 0207-0208
(2019/03/31)
-
- Quinoline-5,8-dione derivatives for TGase 2 inhibitor, and the pharmaceutical composition comprising the same
-
The present invention relates to a quinolin-5,8-dione derivative compound represented by chemical formula I, an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound represented by chemical formula I of the present invention has a TGase 2 inhibitory effect, and the pharmaceutical composition comprising the same can be usefully used for preventing or treating disorders or diseases mediated by TGase 2 or response to TGase 2 inhibition.COPYRIGHT KIPO 2020
- -
-
Paragraph 0455-0458
(2019/10/29)
-
- Study on Relationship Between Fluorescence Properties and Structure of Substituted 8-Hydroxyquinoline Zinc Complexes
-
Organic light-emitting diodes (OLEDs) produced from 8-hydroxyquinoline metal complexes play a vital role in modern electroluminescent devices. In this manuscript, a series of 8-hydroxyquinoline derivatives were synthesized by different methods and their corresponding zinc metal complexes were prepared. The UV and fluorescence properties of the complexes were measured aiming to understand the effect of substituents at the quinoline ring on the fluorescence properties of the complexes. When the C-5 of 8-hydroxyquinoline was replaced by halogen group, the fluorescence emission wavelengths had been red-shifted, at the same time, blue-shifted of fluorescence emission wavelength was observed when the C-5 position of 8-hydroxyquinoline was substituted by electron-withdrawing group. When the C-4 position of 8-hydroxyquinolie was substituted by methyl or the C-5 position was substituted by sulfonic acid group, the corresponding zinc complexes had higher fluorescence intensity than 8-hydroxyquinolie zinc.
- Jianbo, He,Tingting, Zhou,Yongjing, Cao,Yuanyuan, Zhang,Weiqing, Yang,Menglin, Ma
-
p. 1121 - 1126
(2018/08/17)
-
- Quinooxacycloquinone derivative and preparation method thereof, and application of same to antitumor drugs
-
The invention discloses a quinooxacycloquinone derivative and a preparation method thereof, and application of the same to antitumor drugs. The chemical structural formula of quino[1,2-b]oxacyclo-5,6-dione is as described in the specification. In the structural formula, R1, R2, R3 and R4 are independently selected from a group consisting of hydrogen and C1-4 alkyl groups, and n is independently selected from numbers consisting of 0 and 1. The derivative is prepared through a bromination reaction, an oxidation reaction, a substitution reaction, a reduction reaction, a hydrolysis reaction and aring closure reaction. The derivative as shown in the formula has a high reduction metabolism rate under the mediation of the NQO1 enzyme, shows strong antitumor activity, and can be used as an antitumor drug targeting to NQO1.
- -
-
Paragraph 0027; 0028; 0029
(2019/01/08)
-
- A general method for the metal-free, regioselective, remote C-H halogenation of 8-substituted quinolines
-
An operationally simple and metal-free protocol for geometrically inaccessible C5-H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv.), at room temperature. Exceptionally high generality with respect to quinoline is observed, and in most instances, the reaction proceeded with complete regioselectivity. Quinoline with a variety of substituents at the 8-position gave, exclusively, the C5-halogenated product in good to excellent yields. Phosphoramidates, tertiary amides, N-alkyl/N,N-dialkyl, and urea derivatives of quinolin-8-amine as well as alkoxy quinolines were halogenated at the C5-position via remote functionalization for the first time. This methodology provides a highly economical route to halogenated quinolines with excellent functional group tolerance, thus providing a good complement to existing remote functionalization methods of quinolin-8-amide derivatives and broadening the field of remote functionalization. The utility of the method is further showcased through the synthesis of several compounds of biological and pharmaceutical interest.
- Motati, Damoder Reddy,Uredi, Dilipkumar,Watkins, E. Blake
-
p. 1782 - 1788
(2018/02/23)
-
- A SAR study: Evaluation of bromo derivatives of 8-substituted quinolines as novel anticancer agents
-
Background: Brominated 8-hydroxy, 8-methoxy, 8-amino quinolines 5, 6, 8, 9 and novel cyano 8-hydroxyquinolines 11, 12 were evaluated in vitro for their anticancer effects on various cell lines. 5, 7-Dibromo- 5, 7-bromo- 6, 7-cyano- 11 and 5, 7-dicyano-12 8-hydroxyquinolines were shown to have strong antiproliferative activity against various tumor cell lines, including C6 (rat brain tumor), HeLa (human cervix carcinoma), and HT29 (human colon carcinoma) with IC50 values ranged from 6.7 to 25.6 μg/mL. Methods: A structure activity relationship (SAR) was conducted that quinoline core containing hydroxly group at C-8 positon led to more anti cancer potentials. Results: The results of Lactate Dehydrogenase (LDH) cytotoxic, DNA laddering and inhibition assays indicated that 5, 6, 11 and 12 have high cytotoxic effects and appototic potentials. Conclusion: Furthermore, 5 and 12 have inhibitory effects on relaxation of supercoiled plazmid DNA by supressed the Topoisomerase I enzyme. As a result, 5, 6, 11 and 12 may have promising anticancer drug potential and 5 and 12 may be novel topoisomerase inhibitors.
- ?kten, Salih,?akmak, Osman,Tekin, ?aban,K?prülü, Tu?ba Kul
-
p. 1415 - 1424
(2017/12/28)
-
- New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis
-
A set of new aryloxy-quinones were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi and their unspecific cytotoxicity was tested on murine macrophages J-774 cells. Most of these novel compounds were found to be much more potent and selective than the standard drug nifurtimox. Interestingly, 2-phenoxy-naphthoquinone 3b displayed a remarkable nanomolar inhibitory activity, IC50 = 20 nM, and a high selectivity index, SI = 625. The Epc1 was determined for the most interesting compounds and no correlation with the trypanosomicidal effect was found. Therefore, an in silico study was carried out to obtain a pharmacophoric model and quantitative structure-trypanosomicidal activity relationship. The designed pharmacophore recognized the more potent and selective molecules, exhibiting five pharmacophoric features. A correlation coefficient R2 of 0.99 of pIC50 plotted against the predicted values indicated that the 3D-QSAR equation could be applied to further predictions of newly designed trypanosomicidal compounds.
- Vzquez, Karina,Espinosa-Bustos, Christian,Soto-Delgado, Jorge,Tapia, Ricardo A.,Varela, Javier,Birriel, Estefana,Segura, Rodrigo,Pizarro, Jaime,Cerecetto, Hugo,Gonzlez, Mercedes,Paulino, Margot,Salas, Cristian O.
-
p. 65153 - 65166
(2015/08/18)
-
- Synthesis and cytotoxicity studies of some new amino isoquinolin-5,8-dione and quinolin-5,8-dione derivatives
-
During the search for new cytotoxic drugs, a new series of 7-amino-isoquinoline-5,8-dione and 6-amino-quinoline-5,8-dione derivatives have been synthesised starting from isoquinoline, and 8-hydroxy-quinoline, respectively, through multistep reactions. The title compounds 7-amino-isoquinoline-5,8-diones have been prepared by treatment of 6-bromoisoquinoline-5,8-dione with some alkyl/heterocyclic/aromatic amines via nucleophilic tetrahedral mechanism. On the other hand, the corresponding 6-amino-quinoline-5,8-diones have been prepared by treating 7-bromo-quinoline-5, 8-dione with some alkyl/heterocyclic/aromatic amines. Rate of reactions depend on the electron availability on the served aminocompounds (i.e. alkyl/heterocyclic/aromatic amines) during their reactions with the corresponding isoquinoline and quinoline quinones. All synthesised compounds have been purified using a series of chromatographic techniques, and their structures have been characterized by NMR spectroscopy and high resolution EI mass spectrometry. The newly synthesised compounds have been evaluated for cytotoxicity using brine shrimps, demonstrating potent cytotoxic activity (95-100%).
- Abdelwahab, Ahmed B.,Shaaban, Mohamed,Ismail, Mohamed A.H.,Abouzid, Khaled A.M.,Hanna, Atef G.
-
p. 1098 - 1109
(2014/10/15)
-
- Synthesis, characterization and electronic effects investigations of new 5,7-disubstituted tris(8-quinolinolate)Al(III) complexes
-
Eight 5,7-diaryl-8-hydroxyquinoline ligands were synthesized and characterized by 1H, 13C NMR spectroscopy and mass spectrometry. The electron-donating and electron-withdrawing aryl groups were attached to the 5- and 7-positions of the quinolinolate ring via Suzuki coupling reaction. The aluminum complexes of these ligands exhibited successful tuning in the emission color, covering a large segment of the visible spectrum.
- Al-Busafi, Saleh N.,Suliman, Fakhreldin O.,Al-Alawi, Zaid R.
-
p. 138 - 144
(2014/01/17)
-
- New quinoline-5,8-dione and hydroxynaphthoquinone derivatives inhibit a chloroquine resistant Plasmodium falciparum strain
-
We report on the design, synthesis, and in vitro evaluation of new quinoline-5,8-dione and hydroxynaphthoquinone derivatives. The synthesized compounds were evaluated for in vitro antimalarial activity against Plasmodium falciparum. Of the 15 compounds, 7a-c, 8a, 9b, 11, and 15 were effective in growth inhibition with IC50 values of below 5 μM.
- Hussain, Hidayat,Specht, Sabine,Sarite, Salem R.,Hoerauf, Achim,Krohn, Karsten
-
experimental part
p. 936 - 942
(2012/10/08)
-
- An instant and facile bromination of industrially-important aromatic compounds in water using recyclable CaBr2-Br2 system
-
Various industrially-important brominated intermediates have been instantly synthesized using aq. CaBr2-Br2 system as an efficient and recyclable brominating reagent under aqueous conditions at room temperature without the need for metal catalysts or acidic additives. Structurally-diverse phenol and aniline derivatives with strong electron-withdrawing groups such as carboxylic, nitro and formyl show remarkable reactivity to the brominating reagent and brominated in 92-98% yield with high purity (>99%) in a very short reaction time. Organic solvent-free conditions, a feature of the green chemistry, were successively used not only for the reactions but also for the isolation of products at the end of the reaction. The recycling of HBr by its neutralization, thereby generating additional amounts of industrially-important CaBr2 has been designed and developed. The brominating reagent has been recycled and regenerated, and the process was repeated up to 4 cycles after the fresh batch using the regenerated brominating reagent having almost identical selectivity and isolated yields, which seems to be the most promising methodology from the viewpoint of the green approach to organic synthesis.
- Kumar, Lalit,Mahajan, Tanu,Agarwal
-
experimental part
p. 2187 - 2196
(2011/09/16)
-
- A new method of bromination of aromatic rings by an iso-amyl nitrite/HBr system
-
A mixture of iso-amyl nitrite/HBr is shown to be a mild and efficient reagent for electrophilic aromatic bromination. The reaction succeeds with slightly activated arenes and heterocyclic compounds. By using HCl instead of HBr, chlorination can also be performed in few cases. The i-amONO2/HBr mixture can also be utilized for bromination in the α-position of electron withdrawing groups. A possible mechanism is briefly discussed.
- Gavara, Laurent,Boisse, Thomas,Rigo, Beno?t,Hénichart, Jean-Pierre
-
p. 4999 - 5004
(2008/09/21)
-
- QUINOLINE DERIVATIVES
-
The invention relates to new quinoline derivatives which are active CLK-1 inhibitors. More specifically, the CLK-1 inhibitors of the invention are compounds of formula (A). The invention also relates to pharmaceutical compositions comprising such compounds and to methods for the prophylaxis and/or treatment of disorders or their associated symptoms for which the inhibition of CLK-1 is beneficial.
- -
-
Page/Page column 62
(2008/06/13)
-
- Sulfur Nitride in Organic Chemistry. Part 19. Selective Formation of Benzo- and Benzobisthiadiazole Skeleton in the Reaction of Tetrasulfur Tetranitride with Naphthalenols and Related Compounds
-
Tetrasulfur tetranitride (N4S4) reacted with 2-naphthols to afford naphthothiadiazoles (13) in high yields, while 1-naphthols gave naphtholbisthiadiazoles as a major product, together with a small amount of 13.In the reactions with naphthalenediols such as 1,5-, 2,6-, 2,7-, 1,6-, and 1,7-diol, naphtho- or naphthobisthiadiazoles were obtained in varying yields.In some cases, naphthotristhiadiazole was formed as a by-product.In reaction with 5-isoquinolinol, 8-quinolinoles,9H-carbazol-2-ol, and dibenzofuran-2-ol, one and/or two 1,2,5-thiadiazole-ringfused heteroaromatic compounds were obtained.
- Mataka, Shuntaro,Takahashi, Kazufumi,Ikezaki, Youji,Hatta, Taizo,Tori-i, Akiyoshi,Tashiro, Masashi
-
-
- Enzymatic Halogenation of Pyrazoles and Pyridine Derivatives
-
Pyrazole, 1-methylpyrazole and 3-methylpyrazole are chlorinated by the enzyme chloroperoxidase from Caldariomyces fumago, in the presence of potassium chloride and hydrogen peroxide at pH 2.7, yielding the corresponding 4-chloro derivatives in good yields.A 4H-pyrazole is proposed as an intermediate in this reaction. 2-Aminopyridine was converted regiospecifically by the same enzyme into 2-amino-3-chloropyridine, and 8-hydroxyquinoline gave its 5,7-dibromo-derivatives in very good yield when bromide ion was used as halide substrate.
- Franssen, M. C. R.,van Boven, H. G.,van der Plas, H. C.
-
p. 1313 - 1316
(2007/10/02)
-
