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QUINOLONE DERIVATIVE OR SALT THEREOF

A platelet aggregation inhibitor comprising a quinolone derivative or a pharmaceutically acceptable salt thereof as an active ingredient, and a novel quinolone derivative or a pharmaceutically acceptable salt thereof useful as a platelet aggregation inhibitor.

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New pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines: Synthesis, 2D-QSAR, anti-inflammatory, analgesic and ulcerogenicity studies

New pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines were synthesized. A series of ylidene carbohydrazides 14a-i, and hydrazonate 15, were obtained from the prepared 3-carbohydrazide derivative 13. Pyrazole derivatives 12, 16a,b, 18, 19, 20, were also prepared through different reactions. The anti-inflammatory and analgesic activities of all new compounds were evaluated and most of them exerted comparable activity to indomethacin and celecoxib. Ulcer indexes for the most active compounds were calculated and most of them showed less ulcerogenic effect than the reference drugs. The most potent anti-inflammatory compound 12 showed an IC50 of 6.00 mumol/kg and low ulcer index. COX-1/COX-2 activity ratio of compounds 12 and 16b showed almost equal inhibitory effect on both isoenzymes. 2D-QSAR studies revealed good predictive and statistically significant QSAR models.

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AMIDE DERIVATIVE INHIBITOR AND PREPARATION METHOD AND APPLICATION THEREOF

An amide derivative inhibitor and a preparation method and an application thereof. Specifically relating to the compound shown in general formula (I), a preparation method for same, a pharmaceutical composition comprising said compound, and an application of same as an ASK inhibitor for the treatment of neurodegenerative disease, cardiovascular disease, inflammation, autoimmune and metabolic disease, each of the substituents in the general formula (I) being as defined in the description.

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ENANTIOSELECTVE REACTIONS CATALYZED BY CHIRAL TRIAZOLIUM SALTS

This invention provides a convenient method for converting imines and other electrophiles into heterocyclic ring systems. The process does not require the use of metallic reagents, and is catalyzed by an organic heterocyclic carbene catalyst. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. Chiral heterocyclic carbene catalysts of the invention and methods of using these catalysts produce chiral heterocycles in high enantiomeric and diastereomeric excess.

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Pyrroline – Wikipedia,
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ASK1 INHIBITOR COMPOUNDS AND USES THEREOF

Described herein are compounds, including pharmaceutically acceptable salts, solvates, metabolites, prodrugs thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat non-alcoholic steatohepatitis and other diseases characterized by dysfunctional tissue healing and fibrosis.

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Diastereoselective synthesis of cyclic 1,3-aminoalcohols bearing CF3(CCl3)-groups

An aldol-type reaction of cyclic imines and cyclic lactims with carbonyl compounds activated by electron withdrawing trifluoromethyl or trichloromethyl groups proceeded without any catalyst under mild condition. beta-Hydroxymethyl substituted cyclic imines or imidates are formed as a result of the reaction. The reduction of the prepared imines leads stereoselectively to the cyclic 1,3-aminoalcohols. Application of methyl trifluoropyruvate in this transformation opens an opportunity for the synthesis of gamma-aminoacids derivatives which contain pyrrolidine moiety.

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The Chemistry of Lactim Ethers. II. Reaction of Lactim Ethers with 2-Carbethoxymethyl Piperidines

Annulation reactions of methyl valerolactim (2) and methyl caprolactim (3) with cyclic beta-aminoesters, such as 2-carbethoxymethyl piperidine derivatives (4 or 5), often gave two kinds of products apparently arising from the imine and enamine forms of 2 and 3.These chemical properties were consistent with NMR observations of lactim ethers in CD3OD solution.Keywords- lactim ethers; 2-carbethoxymethyl piperidines; imine-enamine tautomeric equilibrium; annulation; imine type product; enamine type product

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Pyrroline – Wikipedia,
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Organic syntheses via transition metal complexes. 96. 1-azacycloalkene and 2-azabicycloalkene derivatives of 4-amino-1-metalla-1,3-dienes by reaction of saturated lactims with (1-alkynyl)carbene complexes of chromium and tungsten

Reaction of five- and six-membered O-alkyl lactims ?(CH2)n-N=C(OR)? 5 (n = 3) and 7 (n = 4) with (1-alkynyl)carbene complexes (CO)5M=C(OEt)C?CPh 1 (a, M = Cr; b, W) gives binuclear 1-alkoxy-2-azabicyclo[n.2.0]alkene derivatives (E)-6 and (E)-8, respectively, in 90-94% yields. Reaction of seven- and eight-membered O-alkyl lactims ?(CH2)n-N=C(OR)? 9 (n = 5) and 11 (n = 6) with compounds 1 affords mononuclear 4-(1-aza-cyclo-2-alken-1-yl) 1-metalla-1,3-butadienes (E)-10 and (E)-11, respectively, but no binuclear derivatives. Both mono- and binuclear metal compounds undergo fast transformations on contact with silica gel. Chromatography of the binuclear tungsten compound (E)-6b on silica gel results in fragmentation of the (cyclobutenyl)carbene unit to give 1,11-bis(tungsta)-5-azaundeca-1,3,6,8,10-pentaene (13) as well as in hydrolysis of the 2-alkoxy pyrrolidine unit with formation of a bis(carbene) derivative 15 of an amino acid. Compound 13, on extended contact with silica gel, undergoes cyclization and subsequent hydrolysis to 2-azabicyclo[3.3.0]octenone 14. Thermal fragmentation of the mononuclear dihydroazepine compound (E)-10c affords dihydro- and tetrahydropyrrolo[1,2-alpha]azepines 17 and 18, respectively. X-ray crystal structural data are reported for the binuclear compound (E)-6b as well as for mononuclear compounds (E)-10c and 14.

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Pyrrolidino enaminones structural related to gyrase inhibitors: Synthesis, cyclization and pharmacological activity

The synthesis and stereochemical characteristics of pyrrolidino enaminones with structural analogy to quinolone antibacterial agents are reported. Retro-aldol reaction of the esters 7 is observed under all conditions of hydrolysis, the enzyme catalyzed reaction also does not yield the corresponding acids. In contrast to clinically used quinolones exemplary tests with monocyclic esters of type 7 and the tricyclic derivative 10 indicate low or no antibacterial activity. Additionally to the lack of the carboxylic acid function the enaminones 7 differ from quinolones in stereochemical demands and the electronic situation of the phenyl substituents of 10, respectively possibly preventing the formation of a co-operative tetrametric system between compounds and DNA bases.

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Synthesis of cytotoxic pyrroloquinazolinoquinoline alkaloid luotonin A

A convenient synthesis of cytotoxic pyrroloquinazolinoquinoline alkaloid, luotonin A (1), was achieved in 3 steps; (i) reaction of anthranilic acid with O-methylbutyrolactim to deoxyvasicinone, (ii) oxidation of deoxyvasicinone, and (iii) formation of luotonin A by the reaction of vasicinone with anthranyl aidehyde.

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