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Ring Chain Transformations. XIV. 3-(omega-Aminoalkyl)-1,2,4-triazoles by Reaction of Isothiosemicarbazides with Lactam Acetals or Lactim Ethers

Isothiosemicarbazide hydrohalides 1 react with lactam acetals 2 or lactim ethers 3 by the formation of lactamisothiosemicarbazones 4 or ring transformed 3-(omega-aminoalkyl)-1,2,4-triazoles 6.The latter can independently by synthesized by alkylation of lactamthiosemicarbazones 9.Condensation of primary 3-(omega-aminoalkyl)-1,2,4-triazoles 6 with lactim ethers 7 can lead to 3-lactamiminoalkyl-1,2,4-triazoles 8.

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Cyclic amidine analogues of taurine and homotaurine: Synthesis and effects on rat skeletal muscle

A series of amidinosulfonic acids IIIa-f, analogs of taurine and homotaurine, was synthesized by reacting 2-aminoethane or 3-aminopropane sulfonic acid with lactim ethers Ia-c and then cyclized to sultams IVa-c and Vd-f. The effects of some selected amidinosulfonic acids III on membrane ionic conductances of rat skeletal muscle are described.

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A Novel Class of “GABAergic” Agents: 1-Aryl-3-(aminoalkylidene)oxindoles

Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles.Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dimethylamino)ethylidene and N-methyl-2-pyrrolidinylidene side chains.The precise mechanism of action of these agents is unclear at this time; however, they are not GABA mimics and they do not affect GABA levels.Like other GABAergic agents, these compounds are potent enhancers of benzodiazepine binding and they antagonize cyclic GMP elevations induced by isoniazid.Compounds from this series may therefore have potential therapeutic utility as anticonvulsants or anxiolytics.

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1-Aza-2-azoniaallene salts: Reactions with azomethines and other N-nucleophiles

Azomethines undergo nucleophilic addition to 1-aza-2-azoniaallene salts 7 to furnish N-(azoalkyl)iminium salts (e.g. 10, 12, 13). With cyclic hydrazones such as pyrazole or indazole, heterocumulenes 7 afford bicyclic 1,2,4,5-tetrazinium salts (e.g. 14, 16), or simple N-adducts such as 15, 17. On the other hand, with open-chain hydrazones azinium salts 19 are formed. Benzotriazole and the aziridine 21 react with 1-aza-2-azoniaallene salts 7 to afford (azoalkyl)ammonium salts 20, 22. The heterocumulenes 7 undergo cycloaddition across the C=N double bond of the azirine 23 to furnish azirenotriazolium salts 25, while with the 1-aza-2-azoniaallene salt 3a the triazolium salt 28 was formed. The constitutions of compounds 22, 25a and 28 were confirmed by X-ray structural analyses.

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Heterocyclic beta-Enamino Esters, 42. Reaction of Heterocyclic beta-Enamino Nitriles with O-Methyllactim Ethers. Dimroth Rearrangement to Novel Heterocondensed Pyrimidophanes

Depending on the ring size of the O-methyllactim ethers employed (4a – f) the heterocyclic beta-enamino nitriles 1 – 3 afford either the linear heterocondensed pyrimidines 5a – d, 6a – f or via Dimroth rearrangement the pyrimidophanes 8 – 13.

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Synthesis and Reactivity of Polyamines: Part 3 – 2,5-Bis-omega-aminoalkylpyrazines and Piperazines

The nitroenamines (1) and (3) on catalytic reduction under acid conditions give rise to the pyrazines (2) and (4) respectively.The pyrazines (2) can be further hydrogenated to the piperazines (10) which show structural similarity to the naturally occuring polyamine, spermine (11).

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Structure-activity relationship studies and biological characterization of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors

The structure-activity relationship (SAR) study of two chemotypes identified as inhibitors of the human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD, 15-PGDH) was conducted. Top compounds from both series displayed potent inhibition (IC50 <50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE 2 production in A549 lung cancer and LNCaP prostate cancer cells. I hope this article can help some friends in scientific research. I am very proud of our efforts over the past few months and hope to 5264-35-7, help many people in the next few years.Application In Synthesis of 5-Methoxy-3,4-dihydro-2H-pyrrole

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COMPOUNDS FOR THE PREVENTION AND TREATMENT OF MEDICAL DISORDERS AND USES THEREOF

Aspects of the invention relate to compounds, pharmaceutical compositions, methods for the manufacturing of compounds and methods for treatment of various disorders mediated at least in part by one or more galectins.

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Synthesis of [1,2-A]-fused tricyclic dihydroquinolines by palladiumcatalyzed intramolecular C-N cross-coupling of polarized heterocyclic enamines

A simple methodology for [1,2-A]-fused tricyclic dihydroquinolines is established. The key ste of the methodology is an intramolecular Buchwald-Hartwig amination reaction of suitabl halogenated (both bromo and chloro) cyclic enaminoketones, enaminoesters and enaminonitrile with various ring size (from five-to seven-membered). Optimal reaction conditions (palladiu source, base, ligand) depend on the ring size of the starting enamine, giving 65-98% yield of th tricyclic product. A treatment of the products with perchloric acid gives respective quinoliniu perchlorates.

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Nonaromatic amidine derivatives as acylation catalysts

(Chemical Equation Presented) Catalytic activity of nonaromatic bicyclic amidines and bicyclic isothioureas in acylation reactions was found to be remarkably dependent on the sizes of both rings. DBN and especially its thia-analogue (THTP) have been identified as highly active acylation catalysts.

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