Series Of Quinoline Research Articles

A novel series of quinoline containing asymmetrically substituted polydiacetylenes for third-order nonlinear optical material

A series of novel unsymmetrical diacetylenes have been prepared which have quinolyl moiety as one of the directly linked sidegroups to the acetylenic backbone. One of the diacetylenes exists in two crystal forms, one of which is solid state reactive. The polydiacetylenes obtained from the monomers have generally long effective conjugation length as indicated by their absorption spectra. The third-order nonlinear optical susceptibility (χ(3)) of one of the polydiacetylenes has been evaluated and found to be in the order of 10−11 esu.

Synthesis and antitumor properties of N-[2-(dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines: a new class of putative topoisomerase inhibitors.

A series of tetracyclic quinoline- and quinoxalinecarboxamides were prepared, and their cytotoxicities were evaluated in a series of murine human tumor cell lines. Most of the quinoline derivatives were prepared by an adaptation of the Pfitzinger synthesis, followed by thermal decarboxylation and coupling with N,N-dimethylethylenediamine via a mixed anhydride method using isobutyl chloroformate. The quinoline analogues showed cytotoxicities broadly similar to those of the known tricyclic acridine-4-carboxamide mixed topoI/II inhibitor DACA, with thieno and indeno analogues being the most active. They showed little decrease in potencies against the Jurkat human leukemia topo II-resistant lines JLA and JLC, suggesting their cytotoxicity does not result primarily from inhibition of topo II. The quinoxaline analogues had more varied IC50 values, being on average less cytotoxic than the quinoline derivatives, but appeared to have a similar mode of action. Overall, this new class of compounds appear to be mixed topo I/II inhibitors, up to 3-fold more cytotoxic than DACA in the human leukemia cell lines studied, with in vivo activity in colon 38 comparable to that of DACA and doxorubicin.

Synthesis of novel heterocycles related to the dynemicin a ring skeleton

AbstractStudies directed towards the construction of the CDE ring framework of dynemycin A (1) are reported. A series of quinoline based dienophiles containing an activating group (e.g. 5, Scheme 1), reacted with acyclic dienes (e.g. 4, Scheme 1) in a Diels‐Alder fashion under increased pressure to afford a variety of heterocyclic systems related to the CDE skeleton of dynemycin A. Reaction of dienophile 15 with cyclic diene 29 led to the novel hetereocycle 34 whereas attempted decarbonylation of 41 led to a novel rhodium‐promoted intramolecular carbonylation of the terminal acetylene furnishing compound 43.

Oxiranes with quinoline substitution : Stereoselective synthesis and antiviral activity

A series of new quinoline substituted oxiranes were synthesised by the reaction of 2-N-(chloroacetyl)-1-(4′-methyl -2′- quinolinyl) hydrazide and aromatic aldehydes. These compounds were tested against encephalomyocarditis virus (EMCV) and only two compounds exhibited protection against the virus.

Studies on disease-modifying antirheumatic drugs: synthesis of novel quinoline and quinazoline derivatives and their anti-inflammatory effect.

In the course of our study aimed at developing new types of DMARDs (disease-modifying antirheumatic drugs), we found that quinoline derivative 1a had a potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting from the potent bone resorption inhibitors justicidins as the lead compounds. Further modification of 1a was performed, and various quinoline and quinazoline derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position of the skeleton were prepared. These compounds were evaluated for anti-inflammatory effects using the AA rat model. Most of these compounds, especially those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2, 4-triazol-1-yl-methyl)quinoline-3-carboxylate (12d), having an ED50 value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po), was selected as a candidate for further investigation. In vitro, 12d inhibited mitogen-induced proliferation at 10(-7)-10(-5) M but not prostaglandin E2 production at 10(-5) M. Moreover, 12d preferentially inhibited the IFN-gamma production by Th1-type clones over the IL-4 production by Th2-type clones. This preferential suppression of Th1 cytokine production is considered the essential immunomodulating action of 12d for the present. Synthesis and structure-activity relationships for this novel series of quinoline and quinazoline derivatives are detailed.

Synthesis and biological activity of carboxyphenylquinolines and related compounds as new potent retinoids. Retinobenzoic acids. VII.

A series of new quinoline, quinolone, and quinazolinedione derivatives was synthesized and tested for retinoid activity in the human promyelocytic cell line HL-60 differentiation assay. All the quinoline compounds exhibited significant activity, depending on the substituent on the heterocycle. However, the quinolone and quinazolinedione derivatives were poor inducers of the differentiation of the HL-60 cells, the activity depending strongly on the polarity of the molecule.

Syntheses and antibacterial activity of novel 6-fluoro-7-(gem-disubstituted piperazin-1-yl)-quinolines

A series of quinoline and naphthyridine antibacterial agents possessing an acyclic or cyclic gem-disubstituted piperazine substituent at the C-7 position have been prepared and evaluated in vitro and in vivo for antibacterial activity against a variety of Gram-positive and Gram-negative organisms. They are, however, not as active as quinolones or naphthyridines with a monosubstituted piperazine substituent at C-7. The chemical synthesis of these derivatives is also described.

Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP +

The in vivo dopaminergic neurotoxicity of a series of quinoline and isoquinoline derivatives was assessed in rats using an intrastriatal microdialysis technique that measures the release of dopamine. The N-methyl quaternary salts of these two heterocyclic aromatic systems displayed about 10% of the potency of MPP + in this assay. Furthermore, tetrahydroisoquinoline, which has been reported to be present in human brain, and N-methyltetrahydroisoquinoline were found to be MAO-B substrates, being oxidized at about 3% the rate of MPTP. Thus, although tetrahydroisoquinoline and N-methyltetrahydroisoquinoline are not neurotoxic, it is conceivable that the chronic endogenous formation of quaternary species could cause neuronal lesions that contribute to the etiology of idiopathic Parkinson's disease.

Some aromatic basic constituents of coal soot

Coal soot has been found to contain a complex mixture of aromatic bases which with one exception fit the three homologous series of pyridine, quinoline and indoline bases.