21638-90-4Relevant academic research and scientific papers
Transition-State Effects in the Divalent Metal Ion Catalysis of Acetal Hydrolysis
Przystas, Theodore J.,Fife, Thomas H.
, p. 4391 - 4396 (1980)
The rates of hydrolysis of a series of substituted benzaldehyde methyl 8-quinolyl acetals have been determined in 50percent dioxane-H2O (v/v) at 30 deg C.The reactions involve hydronium ion catalyzed hydrolysis of the neutral and protonated species.Hammett ρ values are -3.1 and -2.6, respectively.These acetals are also subject to general acid catalysis.Divalent metal ions (Cu2+, Co2+, Ni2+, Mn2+, and Zn2+) exert a large catalytic effect even though binding to the reactant is very weak.For example, a 0.02 M concentration of Ni2+ (1000-fold excess) at pH 7.2 produces a 2x105 enhancement in kobsd for hydrolysis of 3,4-dichlorobenzaldehyde methyl 8-quinolyl acetal, but there is no indication of saturation effects.The rate constants for metal ion catalysis of the hydrolysis of the substituted benzaldehyde methyl 8-quinolyl acetals vary with changing substituents in the same manner as those for the hydronium ion catalysed reactions.At constant metal ion concentration kobsd is pH independent at pH values above the pKa of the quinolone nitrogen.Metal ion catalysis must be due to a transition-state effect in which the leaving group is stabilized.Incorporation of a second functional group which can chelate the metal ion, as in 3,4-dichlorobenzaldehyde 8-(2-carboxyquinolyl) methyl acetal, leads to strong binding to the reactant; i.e., saturation effects are observed at low ion concentrations (10-2-10-3 M), but catalytic effects at >0.01 M metal ion concentration are slightly less than with the 8-quinolyl acetals where reactant binding is weak.This emphasizes the importance of transition-state binding in these reactions.
Electronic spectroscopic characterization of the formation of iron(III) metal complexes: The 8-HydroxyQuinoline as ligand case study
Huyen Vu, Thi,Serradji, Nawal,Seydou, Mahamadou,Brémond, éric,Ha-Duong, Nguyen-Thanh
, (2020)
Synthetic siderophores derivated from 8-HydroxyQuinoline (HQ) present various biological and pharmacological activities, such as anti-neurodegenerative or anti-oxydative. However, their affinity towards iron(III) seems to depend on the position (i.e., 7 or 2) of the HQ substitution by an electron withdrawing group. Two ester-derivatives of HQ at 2- and 7-position are synthesized and their respective iron-complexation is characterized by a joined experimental and theoretical work. By investigating the stability of all the possible accessible spin states of the iron(III) complexes at density-functional theory (DFT) level, we demonstrate that the high-spin (HS) state is the most stable one, and leads to a UV/vis absorption spectrum in perfect match with experiments. From this DFT protocol, and in agreement with the experimental results, we show that the ester functionalization of HQ in 2-position weakens the formation of the iron(III) complex while its substitution in 7-position allows a salicylate coordination of the metal very close to the ideal octahedral environment.
Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: Inhibitors of the neutrophil respiratory burst in a model of gouty arthritis
Pearce, A. Norrie,Chia, Elizabeth W.,Berridge, Michael V.,Clark, George R.,Harper, Jacquie L.,Larsen, Lesley,Maas, Elizabeth W.,Page, Michael J.,Perry, Nigel B.,Webb, Victoria L.,Copp, Brent R.
, p. 936 - 940 (2007)
Ascidiathiazones A (3) and B (4), two new tricyclic thiazine-containing quinolinequinone alkaloids, were isolated from the New Zealand ascidian Aplidium species. Both compounds inhibited the in vitro production of superoxide by PMA-stimulated human neutrophils in a dose-dependent manner with IC50 1.55 ± 0.32 and 0.44 ± 0.09 μM, respectively. In vivo inhibition of superoxide production by peritoneal neutrophils in a murine model of gout was observed for both compounds with oral doses of 25.6 μmol/kg. Ascidiathiazone A (3) was synthesized in four steps from 8-hydroxyquinoline-2- carboxylic acid.
Fluorescent schiff base probes for sequential detection of Al3+ and F? and cell imaging applications
Fu, Jiaxin,Li, Bai,Mei, Huihui,Chang, Yongxin,Xu, Kuoxi
, (2019/11/11)
Two novel Schiff-base fluorescent probers SQ and NQ based on 8-hydroxyquinoline moiety were designed and synthesized. The both probes were capable of binding with Al3+ by naked eye detection to produce a significant fluorescence enhancement response with a detection limit of 1.48 × 10?8 and 4.23 × 10?8 M, respectively. At the same time, the formed complexes SQ-Al3+ and NQ-Al3+ could sequentially detect F?, and the detection limits of F? were determined to be 1.64 × 10?7 and 3.58 × 10?8 M, respectively. The “off-on-off” fluorescence response process demonstrated that the binding were reversible. The probes were further successfully utilized to detect Al3+ and F? in vitro PC12 cells.
Heteroleptic complexes: Via solubility control: Examples of Cu(ii), Co(ii), Ni(ii) and Mn(ii) complexes based on the derivatives of terpyridine and hydroxyquinoline
Baskin, Maria,Fridman, Natalia,Kosa, Monica,Maayan, Galia
, p. 15330 - 15339 (2017/11/22)
We describe the construction of synthetically challenging heteroleptic complexes by capitalizing on the solubility properties of their corresponding favored homoleptic complexes. We demonstrate that the formation of a heteroleptic Cu2+ complex based on 2,2′:6′,2′′-terpyridine (Terpy) and 8-hydroxyquinoline (HQ) is not possible due to the insolubility of (HQ)2Cu2+. Replacing HQ with 8-hydroxy-2-quinolinecarbonitrile (HQCN) enabled the solubility of (HQCN)2Cu2+ in acetonitrile, leading to the formation of the heteroleptic complex Terpy(HQCN)Cu2+, TQCu. Applying these conditions to the synthesis of the corresponding heteroleptic Co2+ complex resulted in TerpyCo2+(acetate)2, which is insoluble in acetonitrile. Upon changing the solvent to methanol, the carbonitrile group of HQCN was converted to carboxyimidate HQOMe yielding a heteroleptic complex Terpy(HQOMe)Co2+, TQ′Co. Using this method, we also generated the heteroleptic complex TQ′Ni and the polynuclear heteroleptic complex Q′4Q′′2Mn4 (Q′′ = HQO2Me). Detailed analysis of the complexes included characterization by X-ray diffraction, EPR, UV-Vis, high resolution ESI MS, DFT calculations and electrochemistry. X-ray analysis of TQCu revealed distorted square pyramidal geometry, while TQ′Co and TQ′Ni exhibit distorted octahedral geometry, which includes metal coordination via the carboxyimidate nitrogen site. Interestingly, Q′4Q′′2Mn4 was found to contain a [MnII4(μ3-O)2(μ2-O)4N10]2+ core, which adopts a distorted octahedral geometry, and two types of HQ chelators. Thus, Q′4Q′′2Mn4 is also heteroleptic even though it does not contain a Terpy ligand. Solution studies revealed that while TQCu is stable in solution, TQ′Co and TQ′Ni go through ligand exchange and are partially converted to their corresponding homoleptic complexes. Based on these data we could propose a mechanism for the formation of TQ′Co and TQ′Ni and show that TQ′Co can be prepared directly from Terpy and HQOMe.
NEW COMPOUNDS
-
Page/Page column 100, (2013/03/26)
There is provided compounds of formula I,wherein R1 R2, X, R3, X1, X2, Xa, Xb, Xc, Xd, Xf, X9 and R4 have meanings given in the description (and which compounds are optionally substituted as indicated in the description), and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease. There is also provided combinations comprising the compounds of formula I.
Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
Boulahjar, Rajaa,Ouach, Aziz,Matteo, Chiurato,Bourg, Stephane,Ravache, Myriam,Guével, Rémy Le,Marionneau, Séverine,Oullier, Thibauld,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
, p. 9589 - 9606 (2013/01/16)
The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.
QUINOLINES AS INHIBITORS OF FARNESYL PYROPHOSPHATE SYNTHASE
-
Page/Page column 54-55, (2009/10/21)
The invention relates to a compound of formula (I) wherein the substituents are as described in the specification, which are useful as farnesyl pyrophosphate synthase modulators, e.g. in the treatment of proliferative diseases, to methods of manufacturing such compounds and to intermediates thereof.
