Showing papers on "Morpholine published in 1995"

Reaction of [60]fullerene with morpholine and piperidine: preferred 1,4-additions and fullerene dimer formation

Abstract: Reactions of an excess of secondary amines with benzene solutions of [60]fullerene in the presence of oxygen lead to dehydrogenated bisadducts and tetraadduct epoxides with a defined 1,4-addition pattern of the amino groups as well as to the first example of an aminated fullerene dimer.

Synthesis and Antitumor Activity of 4- and 5-Substituted Derivatives of Isoquinoline-1-carboxaldehyde Thiosemicarbazone

Abstract: Various substituted isoquinoline-1-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia. Condensation of 4-bromo-1-methylisoquinoline (4) with ammonium hydroxide, methylamine, ethylamine, and N-acetylethylenediamine gave the corresponding 4-amino, 4-methylamino, 4-ethylamino, and 4-N-(acetylethyl)amino derivatives, which were then converted to amides and subsequently oxidized to aldehydes followed by condensation with thiosemicarbazide to yield thiosemicarbazones 8a-c, 9a-c, and 16. Nitration of 4, followed by oxidation with selenium dioxide, produced aldehyde 18, which was then converted to the cyclic ethylene acetal 19. Condensation of 19 with morpholine followed by catalytic reduction of the nitro group and treatment with thiosemicarbazide afforded 5-amino-4-morpholinoisoquinoline-1-carboxaldehyde thiosemicarbazone (22). N-Oxidation of 1,5-dimethylisoquinoline, followed by rearrangement with acetic anhydride, gave, after acid hydrolysis, 1,5-dimethyl-4-hydroxyisoquinoline, which was converted to its acetate and then oxidized to yield 4-acetoxy-5-methylisoquinoline-1-carboxaldehyde (32). Sulfonation of 1,4-dimethylisoquinoline, followed by reaction with potassium hydroxide, acetylation, and oxidation, gave 5-acetoxy-4-methylisoquinoline-1-carboxaldehyde (40). Condensation of compounds 32 and 39 with thiosemicarbazide afforded the respective 4- and 5-acetoxy(5- and 4-methyl)thiosemicarbazones 33 and 40, which were then converted to their respective 4- and 5-hydroxy derivatives 34 and 41 by acid hydrolysis. The most active compounds synthesized were 4-aminoisoquinoline-1-carboxaldehyde thiosemicarbazone (9a) and 4-(methylamino)isoquinoline-1-carboxaldehyde thiosemicarbazone (9b), which both produced optimum % T/C values of 177 against the L1210 leukemia in mice when used at a daily dosage of 40 mg/kg for 6 consecutive days. Furthermore, when 9a was given twice daily at a dosage of 40 mg/kg for 6 consecutive days, a T/C value of 165 was obtained and 60% of the mice were 60-day long-term survivors.

Morpholine derivatives and their use as antagonists of tachikinins

Abstract: The present invention relates to compounds of formula (I): wherein X is N or CH; and pharmaceutically acceptable salts and prodrugs thereof. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.

Synthesis and Biological Evaluation of 5-Fluoro-2'-deoxyuridine Phosphoramidate Analogs

Abstract: A series of alkylating phosphoramidate analogs of 5-fluoro-2'-deoxyuridine has been prepared and their growth inhibitory activity evaluated against murine L1210 leukemia and B16 melanoma cells in vitro. These compounds were designed to undergo intracellular release of the phosphoramidate anions, which it was hoped would function as irreversible inhibitors of thymidylate synthase. The expectation was that binding of the nucleoside moiety would be followed by alkylation of the enzyme via the phosphoramidate. The chloride, bromide, iodide, and tosylate analogs were highly potent inhibitors of L1210 cell proliferation, with increased inhibition observed at both higher drug concentrations and longer exposure times. Addition of thymidine completely reversed the inhibition for all compounds, suggesting that these compounds are acting via inhibition of thymidylate synthase. Although the nonalkylating morpholine analog 1f was ca. 50-fold less potent than the methyl(chloroethyl)amino compound, the piperidine analog 1g was only 2-fold less potent, confirming that nitrogen basicity may be as important as the presence of an alkylating group. Addition of thymidine reversed the growth inhibition of the morpholine and piperidine analogs, suggesting that these compounds may also undergo intracellular conversion to 5-fluoro-2'-deoxyuridine 5'monophosphate. The thymidine and deoxyuridine derivatives 2 and 3 showed minimal growth inhibition in the L1210 assay. The alkylating analogs showed modest cytotoxicity against B16 melanoma cells, and the potency of the analogs was more dependent upon the alkylating moiety than on the 5-substituent.

Method of rinsing showers

Abstract: A method of removing deposits from surfaces of showers and the like without scrubbing or wiping by using a composition that includes a non-ionic surfactant having an HLB of 13 or less, a chelating agent, and optionally, alcohol and/or ammonium hydroxide and/or morpholine

Recording sheets containing oxazole, isooxazole, oxazolidinone, oxazoline salts, morpholine, thiazole, thiazolidine, thiadiazole, and phenothiazine compounds.

Abstract: Disclosed is a recording sheet which comprises a substrate and a material selected from the group consisting of oxazole compounds, isooxazole compounds, oxazolidinone compounds, oxazoline salt compounds, morpholine compounds, thiazole compounds, thiazolidine compounds, thiadiazole compounds, phenothiazine compounds, and mixtures thereof. Also disclosed is a recording sheet which consists essentially of a substrate, at least one material selected from the group consisting of oxazole compounds, isooxazole compounds, oxazolidinone compounds, oxazoline salt compounds, morpholine compounds, thiazole compounds, thiazolidine compounds, thiadiazole compounds, phenothiazine compounds, and mixtures thereof, an optional binder, an optional antistatic agent, an optional biocide, and an optional filler.

Development of potent serotonin-3 (5-HT3) receptor antagonists. I. Structure-activity relationships of 2-alkoxy-4-amino-5-chlorobenzamide derivatives.

Abstract: A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives bearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT 3 ) receptor antagonistic activity by assaying the ability to antagonize the von Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4-thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT 3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)-2-ethoxybenzamide (96) and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT 3 receptor antagonistic activity without 5-HT 4 receptor binding affinity.

Mittel und verfahren zur dauerhaften verformung von keratinfasern

Abstract: The action of an agent for implementing the reducing stage of a process for permanently shaping keratin fibres is enhanced if the agent contains at least one compound selected from heterocyclic compounds (A) from the group formed by imidazol, pyrolidine, piperidine, dioxolane, dioxane morpholine, piperazine and derivatives thereof, and amino acids and their derivatives (B).

Kinetics and products of the photocatalytic degradation of morpholine (tetrahydro-2H-1,4-oxazine) in TiO2 aqueous suspensions

Abstract: Morpholine has been chosen for the study of the TiO2 photocatalytic degradation of saturated heterocyclic compounds in water because it is found in a number of industrial effluents. Its disappearance rate was observed to be much greater with, than without, TiO2 in the UV spectral range. Furthermore, comparison with a variety of aromatic pollutants has shown the high photocatalytic degradability of morpholine, despite its low coverage of the TiO2 surface. Combined GC–MS and HPLC–photodiode-array analyses of the degradation intermediates have shown the formation of hydroxy and oxo derivatives of morpholine and oxidised five-membered ring compounds have shown the formation of hydroxy and oxo derivatives of morpholine and oxidised five-membered ring compounds have been tentatively identified. Intermediates have also been produced by coupling reactions, at least for high initial morpholine concentrations. Two nitrogen-containing aliphatic intermediates (HONHCHCH—O—C2H5 and CH3—NH—CHO) have been found. Finally, low amounts of ethanoate ions and higher amounts of methanoate ions were produced. All the organic intermediates that were formed in amounts sufficient to be monitored were eventually found to be destroyed. Organic nitrogen was initially transformed into ammonium ions.

Intermediates and processes for preparing benzothiophene compounds

Abstract: The present invention provides a novel process for preparing a compound of formula I wherein R¹ and R² combine to form C₄-C₆ polymethylene, -CH₂CH(CH₃)CH₂CH₂-, -CH₂C(CH₃)₂CH₂CH₂-, or -CH₂CH₂OCH₂CH₂-; or a pharmaceutically acceptable salt or solvate thereof, comprising a) reacting a compound of formula II with a compound of formula III wherein R¹ and R² are as defined above, in the presence of triphenylphosphine and diethyl azodicarboxylate; or b) reacting a compound of formula II with a compound of formula Z-CH₃-CH₂-Z in which Z is the same or different leaving group, and reacting the resulting compound of formula IV wherein Z is a leaving group, with pyrrolidine, piperidine, hexamethyleneimine, methylpyrrolidine, dimethylpyrrolidine, or morpholine; c) deprotecting the 6- and 4'-position hydroxy group of the reaction product of step a) or step b); and d) optionally salifying or forming a solvate of the reaction product of step c). Also provided are novel intermediates of formulae II and IV wherein Z is a leaving group.

Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides.

Abstract: Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

Water soluble cyclic amine-dicarboxylic acid-alkanol amine salt corrosion inhibitor

Abstract: Compositions and a method of using the compositions to inhibit corrosion. The compositions are water soluble n-alkyl morpholine, saturated dicarboxylic acid, optionally alkanol amine and optionally surfactant compositions which inhibit ferrous metal corrosion when added to aqueous oxygen-free solutions.

Anthraquinone-photocatalysed addition of amines to α,β-unsaturated esters: a novel route to indolizidone, pyrrolizidone and related ring systems

Abstract: The indolizidone 9, the pyrrolizidone 14, a mixture of heliotridone 15a and pseudoheliotridone 15b and the lactam 19 have been synthesized in a one-step anthraquinone-photocatalysed reaction of the corresponding amines, piperidine 1, pyrrolidine 10 and morpholine 16, with α,β-unsaturated esters.

Structure-activity relationship studies of CNS agents, Part 23: N-(3-phenylpropyl)- and N-[(E)-cinnamyl]-1,2,3,4-tetrahydroisoquinoline mimic 1-phenylpiperazine at 5-HT1A receptors.

Abstract: The 5-HT 1A receptor affinities and ionization constants of a set of 1-arylpiperazine (4) 1,2,3,4-tetrahydroisoquinoline (6), and -quinoline (7) containing N-(ω-arylalkyl) or N-(E)-cinnamyl substituents as well as two morpholine derivatives (8a, 8b) were determined. It was shown that some tetrahydroisoquinoline (6c, 6d) and morpholine (8a) derivatives were 5-HT 1A ligands equipotentto 1-phenylpiperazine (4a) and 1,2,3,4,4a,5-hexahydropyrazino[1,2-a]indole (5). On the basis of molecular modelling studies it was also demonstrated that 6c, 6d and 8a mimicked very well the reference structures of 4a and its rigid analog 5. Another, more complex 1,2,3,4-tetrahydroisoquinoline derivative 3, which served as a model compound to confirm the previously reported 5-HT 1A binding mode of derivatives 1a-d and 2, had the highest 5-HT 1A affinity (K i = 6.7 ± 0.5 nM) of all the investigated compounds

2,3-Dihydrospiro(1H-4- and 5-azabenzimidazole-2,1′-cyclohexane) (= Spiro(cyclohexane-1,2′(3′H)-1′H-imidazo(4,5-b)pyridine) and Spiro( cyclohexane-1,2′(3′H)-1′H-imidazo(4,5-c)pyridine)): Reactions with Nucleophiles.

Abstract: The readily available title compounds 4a and 24 react with N-, O-, S-, and C-nucleophiles in presence of MnO2 to give the corresponding mono- or disubstituted 2H-azabenzimidazoles ( = azaisobenzimidazoles), e.g., 11–18 and 26a–h, respectively, or 2,3-dihydro-1H-azabenzimidazoles ( = dihydro-azabenzimidazoles) such as 9 and 10 and 27 and 28, respectively, by a 1, 4- or 1,6-Michael addition (Schemes 2 and 4). The bromo-dihydro-1H-azabenzimidazole 4b lost the Br-atom when treated with piperidine or morpholine yielding the corresponding disubstituted 2H-azabenzimidazole 21 (Scheme 3). Reductive ring opening of the substituted spiro compounds leads to mono- and disubstituted diaminopyridines which are intermediates for fused pyridine ring systems with substituents often not available by conventional routes and of potential pharmaceutical interest (see 32–37). E.g., starting from 4a, a three-step synthesis of the analgesic flupirtine maleate (= ethyl {2-amino-6-[(4-fluorobenzyl)amino]pyridin-3-yl}carbamate maleate = Katadolon®; 39) and of its non-fluorinated derivative D-7195 is described. Its analogue 40 was similarly made from the spiro compound 24.

Equilibres liquide-vapeur isothermes de melanges binaires formes de composes heterocycliques tels que: Morpholine, tetrahydropyranne, piperidine et 1,4-dioxane

Abstract: The authors have measured the vapour pressure of four binary systems, morpholine+piperidine, morpholine+1,4-dioxane, morpholine+tetrahydropyrane and 1,4-dioxane+tetrahydropyrane. The measurements were carried out using an isoteniscope built by J. Jose [1]. The vapour pressure, excess Gibbs free energies at 298.15, 303.15, 313.15, 323.15, 333.15 and 343.15 K are reported for these mixtures. The excess Gibbs free energies have been fitted to the Redlich-Kister equation.

Synthesis and Biological Activity of Some 5-Substituted-6-azauracil-N-1-Nucleosides of 2-Acetamido-2-Deoxy-D-glucose

Abstract: Glycosylation of the silylated 5-bromo- and 5-benzylmercapto-6-azauracil 1 and 2, respectively, with the acylated sugar 3 afforded 1-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-s-D-glucopyranosyl)-5-bromo-6-azauracil 4 and its 5-benzylmercapto analogue 6. Deblocking of 4 and 6 gave the free nucleosides 5 and 7, respectively. Alternatively, 6 was obtained from reaction of benzylmercaptan with 4 in pyridine. Reaction of 4 with morpholine, 2,4-dichlorobenzylamine and N-methylethanolamine gave the 5-alkylamino derivatives 8, 10 and 11, respectively. Deblocking of 8 gave the nucleoside 9. All the newly synthesized compounds were characterized by their 1HNMR, U.V. and mass specta. Compounds 5, 7, 9, 10 and 11 were tested for their activity against HIV type 1 and 2, but they did not show significant biological activity and not toxic at 100 mcg/mL. The antimutagenic activity of 5 and 7 is under investigation.