SEARCH · PubMed Health

Results for “MORPHOLINES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed2006

Judicious application of allyl protecting groups for the synthesis of 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl triflate, a key precursor of DNA-dependent protein kinase inhibitors.

[Structure: see text] 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl 2,2,2-trifluoromethanesulfonate is a key intermediate for the synthesis of the DNA-dependent protein kinase (DNA-PK) inhibitor 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441). Two improved methods for the synthesis of this triflate have been developed: (A) in 35% overall yield, through modification of the published route, and (B) in 15% overall yield, by a new route employing a Baker-Venkataraman rearrangement to enable generation of the chromenone scaffold. Both syntheses depend on the judicious use of allyl protecting groups.

Benzopyrans↗

PubMed1997

Derivatization and template-guided ligation of oligodeoxyribonucleotides using cyanogen bromide and N-substituted morpholines.

Cyanogen bromide has been found to induce the template-guided condensation of oligonucleotides only in the presence of N-substituted morpholines. Based on 31P, 1H and 13C NMR spectroscopy data, the mechanism of the phosphomonoester group activation by cyanogen bromide in N-substituted morpholine buffers is suggested. It has also been shown that BrCN can be used for the synthesis of oligonucleotide derivatives in aqueous solution.

Buffers↗

PubMed2003

Local anaesthetic effects and toxicity of seven new diethanolamine and morpholine derivatives of fomocaine. Testing in rats compared with procaine and tetracaine.

Fomocaine (CAS 56583-43-8) is a local anaesthetic (LA) with long lasting surface effect and low toxicity. Nevertheless, it is not optimal yet. Therefore, 7 newly synthesised derivatives, 4 diethanolamines (OE 6000, OE 7000, OE 8000, OE 9000) and 3 morpholines (OE 500, OE 1000, OE 5000) were compared with procaine-HCl (CAS 51-05-8) and tetracaine-HCl (CAS 136-47-0) in rats. Based on standard methods for the testing of LA effects and using two methods for characterising side effects and toxicity of LA (paresis of the N. ischiadicus, LD50) it can be concluded that: a) The very good surface anaesthesia caused by especially fomocaine and tetracaine could be stated but concerning conduction anaesthesia procaine is better qualified. b) Concerning conduction anaesthesia, diethanolamine derivatives are more potent compared to morpholine derivatives. c) Surface anaesthesia shows a different picture: the effect of fomocaine is in between. d) The paresis of the N. ischiadicus as a first sign of toxic side effects indicated that low effect is combined with short paresis. e) Compared to the LD50 of fomocaine, the toxicity of OE 500 and OE 5000 is only one half. On the basis of the experiments with fomocaine derivatives, distinct structure-activity relationships could be demonstrated for fomocaine derivatives concerning a) LA effects and b) toxicity. Altogether OE 9000 could be a promising candidate for systemic use.

Administration, Topical↗

PubMed1975

Aerial application of N-trityl morpholine to irrigation canals in Sudan.

Using a crop-spraying aircraft modified to give a coarse spray, the feasibility of aerial application of the molluscicide N-trityl morpholine to minor canals on the Gezira has been proved. In January 1973, seven canals were sprayed at dosages of 0-1 p.p.m., 0-2 p.p.m., 0-5 p.p.m. and 1-0 p.p.m. Chemical analysis indicated that about 70% of the chemical was present in the water 5-15 hours after the spray, and snail exposure to the sprayed canals indicated that all dosages applied were lethal to Biomphalaria snails. Bulinus snails, which are less susceptible to the molluscicide, were killed only by the 0-5 p.p.m. and 1-0 p.p.m. dosages. Sampling of the natural snail populations of the canals confirmed these results. In March 1973, an area of 464 sq km was treated by drip-feed of 0-1 p.p.m. N-trityl morpholine to kill snails in the main and major canals, and then by aerial spraying 56 of the 58 minor canals in the area. Despite the high winds which disrupted the spray timetable, the canals were successfully treated in 9-5 hours flying-time within seven days. A very high initial snail kill was indicated by both caged snail exposure and natural snail population sampling. However, in excellent snail breeding conditions the area was reinfested with snails within two months. The cost of the application was only 5% of the chemical cost, and aerial spraying in March and May will almost certainly be incorporated in an annual snail control programme.

Aircraft↗

PubMed1998

N-borane-N-(trimethylsilyl)morpholine.

The title compound, C7H20BNOSi, features an N,N-disubstituted six-membered morpholine ring in a chair conformation, with the trimethylsilyl group in the equatorial position and the borane group in the axial position. The least-squares plane formed by the four C atoms of the morpholine ring has a mean deviation of 0.013 (2) A. The O and N atoms are 0.672 (2) and 0.650 (2) A above and below the plane, respectively.

Boron Compounds↗

PubMed1988

Studies of the reactivity of morpholine, 2-mercaptobenzothiazole and 2 of their derivatives with selected amino acids.

Previous studies in guinea pigs showed that DTDM, MMBT and MBT were sensitizing agents. The purpose of this study was to investigate the biochemical basis of this sensitization reaction. The reactions of representative amino acids, Cys, Lys & Gly, with morpholine, DTDM, MMBT & MBT were examined. New compounds were found between MMBT and all 3 amino acids. Additional new compounds were seen for Cys/MBT, Cys/DTDM, Lys/MBT & Gly/DTDM. No reaction was observed with morpholine. The new compounds were examined spectroscopically. Results suggest that the sensitizing nature of DTDM is probably a reaction of its disulfide bond with the -SH & -NH2 groups of amino acid moieties. The conjugation of Cys/MMBT may be via the same reaction mechanism. The -SH group of MBT may react either via oxidation and/or thioester formation with the carboxylate group of amino acids. These results also suggest that in vitro tests may predict the sensitizing potential of certain compounds.

Amino Acids↗

PubMed2005

Kinetic and binding studies with purified recombinant proteins ferredoxin reductase, ferredoxin and cytochrome P450 comprising the morpholine mono-oxygenase from Mycobacterium sp. strain HE5.

The P450mor system from Mycobacterium sp. strain HE5, supposed to catalyse the hydroxylation of different N-heterocycles, is composed of three components: ferredoxin reductase (FdRmor), Fe3S4 ferredoxin (Fdmor) and cytochrome P450 (P450mor). In this study, we purified Fdmor and P450mor as recombinant proteins as well as FdRmor, which has been isolated previously. Kinetic investigations of the redox couple FdRmor/Fdmor revealed a 30-fold preference for the NADH-dependent reduction of nitroblue tetrazolium (NBT) and an absolute requirement for Fdmor in this reaction, compared with the NADH-dependent reduction of cytochrome c. The quite low Km (5.3 +/- 0.3 nm) of FdRmor for Fdmor, measured with NBT as the electron acceptor, indicated high specificity. The addition of sequences providing His-tags to the N- or C-terminus of Fdmor did not significantly alter kinetic parameters, but led to competitive background activities of these fusion proteins. Production of P450mor as an N-terminal His-tag fusion protein enabled the purification of this protein in its spectral active form, which has previously not been possible for wild-type P450mor. The proposed substrates morpholine, piperidine or pyrrolidine failed to produce substrate-binding spectra of P450mor under any conditions. Pyridine, metyrapone and different azole compounds generated type II binding spectra and the Kd values determined for these substances suggested that P450mor might have a preference for more bulky and/or hydrophobic molecules. The purified recombinant proteins FdRmor, Fdmor and P450mor were used to reconstitute the homologous P450-containing mono-oxygenase, which was shown to convert morpholine.

Catalysis↗

PubMed2000

Common degradative pathways of morpholine, thiomorpholine, and piperidine by Mycobacterium aurum MO1: evidence from (1)H-nuclear magnetic resonance and ionspray mass spectrometry performed directly on the incubation medium.

In order to see if the biodegradative pathways for morpholine and thiomorpholine during degradation by Mycobacterium aurum MO1 could be generalized to other heterocyclic compounds, the degradation of piperidine by this strain was investigated by performing (1)H-nuclear magnetic resonance directly with the incubation medium. Ionspray mass spectrometry, performed without purification of the samples, was also used to confirm the structure of some metabolites during morpholine and thiomorpholine degradation. The results obtained with these two techniques suggested a general pathway for degradation of nitrogen heterocyclic compounds by M. aurum MO1. The first step of the degradative pathway is cleavage of the C---N bond; this leads formation of an intermediary amino acid, which is followed by deamination and oxidation of this amino acid into a diacid. Except in the case of thiodiglycolate obtained from thiomorpholine degradation, the dicarboxylates are completely mineralized by the bacterial cells. A comparison with previously published data showed that this pathway could be a general pathway for degradation by other strains of members of the genus Mycobacterium.

Biodegradation, Environmental↗

PubMed1990

Spectroscopic analysis of charge transfer complexes between morpholine and iodine.

It has been demonstrated spectroscopically that many nitrogen-containing heterocyclic compounds can form charge transfer complexes with iodine. The complexes of morpholine with iodine were shown to be of the n-sigma type with a 1:1 stoichiometry. A strong donor-acceptor interaction was found (Kc = 1261 +/- 12 mol-1 at 20 degrees C in CCl4), considerably higher than those of complexes of aromatic compounds with iodine. The high value of the formation constant for this complex indicated that morpholine could serve as a starting point for the synthesis of novel anti-thyroid drugs.

Antithyroid Agents↗

PubMed1983

Liver and forestomach tumors and other forestomach lesions in rats treated with morpholine and sodium nitrite, with and without sodium ascorbate.

Administration to rats of ascorbate with morpholine and nitrite was previously shown to inhibit the liver tumor production and to enhance the induction of forestomach tumors, as compared to treatment with morpholine and nitrite. In a repetition of this experiment, 10 g morpholine/kg in the diet and 2 g sodium nitrite/liter in the drinking water were administered for life to male MRC-Wistar rats without (group 1) or with (group 2) 22.7 g sodium ascorbate/kg in the diet. Group 3 was untreated. Group 2 showed a lower liver tumor incidence with a longer latency than group 1, indicating a 78% inhibition by ascorbate of in vivo N-nitrosomorpholine (NMOR) formation. The incidence of forestomach papillomas was 3% in group 1, 38% in group 2, and 8% in group 3. The difference between groups 1 and 2 was not significant due to the shorter life-span of group 1. Group 1 and especially group 2 had more forestomach hyperplasia and hyperkeratosis than group 3. Ascorbate might have enhanced induction of these lesions because of an action synergistic with that of NMOR. However, it is most likely that the lowered NMOR dose and concomitantly increased survival produced by the ascorbate were solely responsible for the increased incidence of forestomach papillomas and other lesions in group 2.

Animals↗

PubMed1980

In vivo nitrosation of morpholine in mice by inhaled NO2.

Groups of 3-5 mice were gavaged with aqueous solutions of 2 mg morpholine and immediately exposed to 2-50 ppm levels of NO2 in inhalation chambers for periods of up to 3 hours. After exposure, mice were frozen and pulverized in liquid nitrogen, and aliquots of frozen powder (congruent to 8 g) were extracted with cold 35% aqueous methanol and methylene chloride. Concentrated methylene chloride solutions were analyzed for N-nitrosomorpholine (NMOR), using gas chromatography with a Thermal Energy analyzer detector. NMOR levels in controls (exposed to NO2 alone, or dosed with morpholine without subsequent NO2 exposure) were less than 5 ng/mouse. NMOR yields in test mice were time-dependent with respect to duration of NO2 exposure and dose-dependent with respect to NO2 levels. These preliminary studies demonstrate the in vivo nitrosating potential of nitrogen oxides.

Animals↗

PubMedDate not supplied

The orally active renin inhibitor A-74273. In vivo and in vitro morpholine ring metabolism in rats, dogs, and humans.

The metabolism and disposition of [14C]A-74273--a potent, orally active renin inhibitor--were investigated in beagle dogs and Sprague-Dawley rats. Two male and two female dogs received a single 10 mg/kg oral or 1 mg/kg intravenous dose in a cross-over experiment and urine and feces were collected for 5 days. After both intravenous and oral dosing, > 92% of the dose was recovered in the feces and < 3% was recovered in the urine. The predominance of hepatobiliary elimination in the clearance of A-74273 was verified in a bile-exteriorized dog, where 79.8% of a 1 mg/kg intravenous dose was excreted in the bile within 6 hr after administration. Similarly, administration of a 1 mg/kg intravenous dose to a bile-exteriorized rat resulted in biliary excretion of 60.5% of the dose within 6 hr. Radio-HPLC analysis of bile and feces from both species indicated extensive metabolism of A-74273 to three major morpholine ring-opened metabolites; the ethanolamine A-78242, the amine A-78030, and the carboxylic acid A-81307. These three metabolites each contributed 12.0-20.2% of the biliary radioactivity after intravenous dosing, while unchanged A-74273 contributed 5-17%. Incubation of [14C]A-74273 with rat, dog, and human liver microsomes afforded nearly equal amounts of the three in vivo metabolites for all three species, suggesting that the in vitro system was representative of A-74273 in vivo metabolism and that humans should also convert A-74273 to the morpholine ring-opened metabolites in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed2005

Synthesis and antimicrobial activity of some 5-[2-(morpholin-4-yl)acetamido] and/or 5-[2-(4-substituted piperazin-1-yl)acetamido]-2-(p-substituted phenyl)benzoxazoles.

In this study, a series of twelve novel 5-[2-(morpholin-4-yl)acetamido] and/or 5-[2-(4-substituted pip-erazine-1-yl)acetamido]-2-(p-substituted phenyl]benzoxazole derivatives have been synthesized and their structures were confirmed by IR, (1)H NMR, and mass spectral data. These compounds were prepared by reacting 5-(2-chloroacetamido)-2-(4-p-substituted-phenyl)benzoxazoles, which were obtained by using 5-amino-2-[p-substituted-phenyl]benzoxazoles with chloroacetyl chloride, in the presence of morpholine or 1-substituted piperazines. All synthesized compounds 3-14 were tested by using the method of twofold serial dilution technique for in vitro activities against certain strains of Gram-positive, Gram-negative bacteria as well as the yeasts Candida albicans, Candida krusei, and Candida glabrata in comparison with standard drugs. Microbiological results showed that the newly synthesized compounds possessed a broad spectrum of activity, showing MIC values of 3.12-50 mug/mL against the Candida species.

Anti-Bacterial Agents↗

PubMed2003

Structure-activity relationships of the p38alpha MAP kinase inhibitor 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naph- thalen-1-yl]urea (BIRB 796).

We report on the structure-activity relationships (SAR) of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]urea (BIRB 796), an inhibitor of p38alpha MAP kinase which has advanced into human clinical trials for the treatment of autoimmune diseases. Thermal denaturation was used to establish molecular binding affinities for this class of p38alpha inhibitors. The tert-butyl group remains a critical binding element by occupying a lipophilic domain in the kinase which is exposed upon rearrangement of the activation loop. An aromatic ring attached to N-2 of the pyrazole nucleus provides important pi-CH(2) interactions with the kinase. The role of groups attached through an ethoxy group to the 4-position of the naphthalene and directed into the ATP-binding domain is elucidated. Pharmacophores with good hydrogen bonding potential, such as morpholine, pyridine, and imidazole, shift the melting temperature of p38alpha by 16-17 degrees C translating into K(d) values of 50-100 pM. Finally, we describe several compounds that potently inhibit TNF-alpha production when dosed orally in mice.

Animals↗

PubMed2000

Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity.

In this investigation, we study the synthesis and the evaluation of antioxidant and hypocholesterolemic activity of a number of 2-biphenylyl morpholine derivatives, which are structurally similar to some substituted morpholines possessing antioxidant activity, as well as to hypocholesterolemic 3-biaryl-quinuclidines. The novel derivatives are found to inhibit the ferrous/ascorbate induced lipid peroxidation of microsomal membrane lipids, the most potent derivative, 2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol (compound 7), having an IC(50) value of 250 microM. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound (7) decreases total cholesterol, low density lipoprotein, and triglycerides in plasma of Triton WR-1339 induced hyperlipidemic rats by 54%, 51%, and 49%, respectively, at 28 micromol/kg (ip). The above results indicate that the new molecules may be proven useful as leads for the design of novel compounds as potentially antiatherogenic factors.

Animals↗

PubMed2004

Efficient synthesis of acylsilanes using morpholine amides.

[reaction: see text] A general synthesis of acylsilanes from the corresponding morpholine amides and silyllithium species is described. The use of morpholine amides is economical and prevents over-addition by the silyl nucleophile. The procedure cleanly affords acylsilanes in good yields and circumvents the use of stoichiometric copper(I) cyanide typically employed to synthesize these compounds from acid chlorides.

Journal Article↗

PubMed2005

Cytotoxicity and detection of damage to DNA by 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c] quinazoline on human cancer cell line HeLa.

Quinazolines - 1,3-benzodiazines are biological active compounds, which are used in the phamaceutical industry, in agriculture and in the medicine. As documented in the literature, many derivatives demonstrated anticancer activity and they act as multitarget agents. 3-(5-Nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c] quinazoline (NTCHMTQ) - a new synthetically prepared quinazoline derivative was the most effective derivative in our primary cytotoxic screening. In this study, we evaluated cytotoxic/antiproliferative activity of NTCHMTQ using human tumor cell line HeLa. Possible interaction of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c] quinazoline with calf thymus DNA was tested by the DNA - modified screen - printed electrode. Quinazoline derivative acted cytotoxically on tumor cell line HeLa. The IC(100) value was 10 microg/ml. The IC(50) values was found to be less than 4 microg/ml, a limit put forward by the National Cancer Institute (NCI) for classification of he compound as a potential anticancer drug. Quinazoline at micromolar concentrations induced morphological changes and necrosis of HeLa cells. Using the DNA based electrochemical biosensor, we have not found damage to DNA under in vitro conditions at an incubation of the biosensor in mixture with quinazoline.

Animals↗

PubMed1990

Lipophilicity of some substituted morpholine derivatives synthesized as potential antinociceptive agents.

Some substituted 2-alkoxy-morpholines have been synthesized as potential antinociceptive agents. These compounds share some structural characteristics of the piperidine analgesics. Their lipophilicity, expressed as log P (octanol-water) and as RM values (from reversed phase thin layer chromatography) was determined. Correlation of these two lipophilicity parameters indicated the classification of the tested compounds into two subgroups. Acute toxicity and, for some selected structures, analgesic activity are reported.

Analgesics↗