Propyl Moiety Research Articles

Pharmacokinetics of intravenous and oral prethcamide in horses

The respiratory stimulant prethcamide is a mixture of equal parts of crotethamide and cropropamide. A specific and sensitive gas chromatographic method for the determination of crotethamide and cropropamide in horse plasma and urine is described. Both components of prethcamide were extracted from plasma and urine into dichloromethane. The extracts were analyzed by capillary gas chromatography with thermionic detection in the nitrogen-specific detection mode. The lower limits of quantitation were 4.0 ng ml −1 of plasma and 10.0 ng ml −1 of urine. Calibration curves were linear from 2.0–100 ng ml −1 of plasma for both components. Pharmacokinetic parameters for crotethamide and cropropamide after intravenous and oral dosing were estimated by analysis of plasma concentration versus time data. The total plasma clearance of cropropamide was greater than that of crotethamide and both values were greater than 5 ml min −1 kg −1. Renal clearance values of the two drugs were comparable and were much less than estimates of filtration clearance values in horses, indicating extensive re-absorption of both components from the renal tubules. Both compounds were metabolized by N-demethylation of the [(dimethylamino)-carbonyl]-propyl moiety and these metabolites were excreted in urine. The method was demonstrated to be suitable for detecting illicit administration of prethcamide to competition horses.

Synthesis and structures of intramolecularly hexacoordinated organotin chlorides containing the (3-(2-methoxy)ethoxy) propyl moiety

Two water-soluble organotin compounds, (3-(2-methoxy)ethoxy)propyltin trichloride, 1, and bis (3-(2-methoxy)ethoxy)propyltin dichloride, 2, were synthesized and characterized by 1H, 13C and 119Sn NMR spectroscopy and by X-ray diffraction. In both cases, the geometry at the tin atom is that of a distorted cis-octahedron, which is preserved for both compounds in CDCl 3 solution. A detailed solution structure is proposed for 1 from ID 1H- 119Sn HMQC NMR experiments.

Characterization by Pyrolysis/Gas Chromatography/Mass Spectrometry of the Alkalilignin Obtained from Wheat Straw Soda-cooking Effluents After Treatment withStreptomycesStrains

Alkalilignin samples obtained from untreated paper-mill effluent and effluent decolorized by Streptomyces UAH 30 and Streptomyces UAH 51 were analyzed by pyrolysis/gas chromatography/mass spectrometry. The molecular composition of the samples and the chemical modifications occurring in the lignin units were studied in order to know the mechanism of decolorization carried out by these microorganisms. The pyrolysis data showed a notable reduction in the lignin pyrolysis products of alkalilignins in effluent decolorized by Streptomyces strains. Moreover, chemical modifications, such as oxidation and shortening of the side chain of the phenyl–propyl moieties of lignin were also detected.

Alkylation of phenol with 1-propanol and 2-propanol over catalysts derived from hydrotalcite-like anionic clays

Vapour phase alkylation of phenol with 1-propanol and 2-propanol was carried out in a fixed-bed flow reactor over calcined magnesium aluminium hydrotalcites (MgAl-CHT) with Mg/Al atomic ratios 2, 3 and 4. MgAl 3.0-CHT showed higher phenol conversion (∼80% at 350‡C, in the alkylation of phenol with 1-propanol. Both O- and C-alkylations were found to be taking place without any skeletal isomerization of the propyl moiety, suggesting an SN2 type mechanism. Isomorphous substitution of Mg2+ by Cu2+ or Ni2+ in the hydrotalcite framework resulted in the predominant C-alkylation to give 2-n-propylphenol (60–70%) with nearly 40–50% phenol conversion at 350‡C. When 2-propanol was used as an alkylating agent, the phenol conversion decreased over all these catalysts and the alkylation was noticed exclusively at C-centers. Comparison of the product selectivity at constant phenol conversion revealed that CuAl 3.0-CHT is more selective for 2-n-propylphenol and 2-isopropylphenol in the reaction of phenol with 1-propanol and 2-propanol respectively. The participation of a pair of acid-base sites in the calcined hydrotalcites for the alkylation reaction has been proposed. The acid-base properties of these catalysts have been examined by the decomposition of cyclohexanol as a test reaction. Analysis of the spent catalysts revealed that Cu2+ in CuO gets reduced into Cu1+ and metallic copper during the reaction in the case of CuAl-CHT, while MgO and NiO phases of MgAl-CHT and NiAl-CHT are retained.

Stress induction of the spermidine/spermine N1-acetyltransferase by a post-transcriptional mechanism in mammalian cells

Heat shock and diethyldithiocarbamate stimulate polyamine catabolism in animal cells by a mechanism involving the induction of spermidine/spermine N1-acetyltransferase (N1-SSAT) activity. Steady-state levels of RNA encoding this enzyme remain essentially unchanged during periods after these stresses when N1-SSAT activity is increased by 3.5-10-fold or more in three different cell lines of hamster and human origin. Depletion of intracellular spermidine pools by alpha-difluoromethylornithine (DFMO) inhibits stress induction of N1-SSAT activity. Exogenous spermidine can restore stress inducibility of N1-SSAT to DFMO-treated cells, and induce this enzyme activity in non-heat-shocked but polyamine-depleted cells. Acetylation at N1 suppresses the ability of spermidine to induce N1-SSAT activity, relative to this same modification at N8. Fluorinated spermidine analogues, which decrease the pKa values of the amine groups at positions 4 and 8, neither induce nor inhibit N1-SSAT activity in DFMO-treated cells. These data demonstrate that certain stresses induce N1-SSAT by a spermidine-dependent post-transcriptional mechanism. The mode of induction is affected by both the propyl and butyl moieties of spermidine.

ChemInform Abstract: Studies on Hypotensive Agents. Synthesis of 1‐Substituted 3‐(2‐Chlorophenyl)‐6‐ethoxycarbonyl‐5,7‐dimethyl‐2,4 (1H,3H)‐quinazolinediones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies on Hypotensive Agents. Synthesis of 1-Substituted 3-(2-Chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H,3H)-quinazolinediones.

3-(2-Chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H,3H)-quinazoline dione was newly prepared. 1-Hydrogen atoms of the compound were variously substituted in order to test for their hypotensive activities on relaxing effects of the blood vessels. The compounds with 2-(1-pyrrolidinyl) ethyl, 2-(1-piperidinyl)ethyl, 3-(dimethylamino)propyl, and 3-(N-benzyl-N-methylamino)propyl moieties showed significant activity. The 2-(1-piperidinyl)ethyl compound possessed activity approximately 23 times more potent than papaverine, however, it was less potent than cinnarizine.

Conformation and intermolecular interation of the antidepressant drugs nitroxazepine and imipramine in aqueous solutions and model membranes

AbstractComplete assignments of the proton magnetic resonance spectra of nitroxazepine and imipramine have been made using 1D and 2D techniques. The drugs are found to aggregate through stacking intereactions between the tricyclic moieties at higher concentrations in aqueous solutions. The changes in the chemical shifts with increasing concentration of the two antidepressant drugs show qualitative agreement with the stacking patterns and conformations observed in crystal structures. The conformations of the propyl moiety of the two drugs in aqueous solution and in lipid bilayers are very different. In D2O, the drugs exist in an extended chain conformation which is similar to the crystal structure. In lipid bilayers they acquire a folded structure. The folded structures probably facilitate the binding of the hydrophobic regions of the drugs to the interior of lipid bilayers.

Characterization of two metabolites of prethcamide by gas chromatography and mass spectrometry.

Crotethamide and cropropamide, both components of the respiratory stimulant prethcamide, are metabolized in humans by demethylation of the [(dimethylamino)-carbonyl]-propyl moiety. The resulting metabolites are characterized by gas chromatography-mass spectrometry of urinary extracts. The use of HCl to prevent losses by volatilization during the evaporation step, combined with methanol as solvent, complicates gas liquid chromatographic analysis of prethcamide. The resulting artifacts are identified.

Metabolism in vitro of tris(2,3-dibromopropyl)- phosphate: Oxidative debromination and bis(2,3- dibromopropyl)phosphate formation as correlates of mutagenicity and covalent protein binding

Tris(2,3-dibromopropyl)phosphate (Tris-BP) was found to be metabolized by liver microsomes obtained from untreated and phenobarbital-pretreated rats. Metabolites of Tris-BP, whose formation was dependent on NADPH and oxygen, included bromide ion and bis(2,3-dibromopropyl)-phosphate (Bis-BP). The rates of formation of these metabolites were markedly increased in liver microsomes isolated from phenobarbital-pretreated rats compared to microsomes from untreated rats. In the presence of either SKF 525-A or metyrapone, the formation rates of bromide ion and Bis-BP were decreased, whereas α-naphthoflavone had no effect. The effects of the various treatments on bromide release and Bis-BP formation paralleled those that have been previously observed with respect to the activation of Tris-BP to mutagenic and covalently protein bound metabolites. Furthermore, rates of oxidative debromination of several Tris-BP analogs directly correlated with their respective mutagenicities. Addition of glutathione (GSH) to microsomal incubations of Tris-BP increased bromide release substantially over control, values but had no effect on Bis-BP formation. On the other hand, the addition of GSH to microsomes decreased covalent binding and mutagenicity of Tris-BP with increased formation of water soluble metabolites. GC/MS analysis of ethyl acetate extracts from incubations of rat liver microsomes with Tris-BP identified 2-bromoacrolein (2-BA) as a metabolite. Introducing deuterium at the carbon atom number 1 of the propyl moiety of Tris-BP had no effect on either bromide release or mutagenicity, whereas the analog labelled at carbon atom 3 showed significant isotope effects on both activities. In contrast, deuterium substitution at carbon atom 2 gave a significant isotope effect on bromide release, but not on mutagenicity. The data indicate that Tris-BP can be metabolized by rat liver microsomes to Bis-BP and 2-bromoacrolein catalyzed by cytochrome P-450 in a process liberating bromide ions. Further, the results are consistent with oxidation at the terminal carbon atom of Tris-BP thereby forming 2-bromoacrolein, which is postulated to be the metabolite mainly responsible for Tris-BP mutagenicity.

Synthesis, characterization, and diels–alder extension of cyclopentadiene telechelic polyisobutylene. IV. α,ω-Di(3-cyclopentadienylpropyldimethylsilyl)polyisobutylene

The synthesis and chain extension of polyisobutylene having nonfluxional terminal cyclopentadiene groups is described. The fluxional behavior of silylcyclopentadiene end groups was previously found to prevent Diels–Alder dimerization of the end groups. The incorporation of a propyl moiety between the silicon atom and the cyclopentadiene ring was found to prevent this fluxional isomerization. Polyisobutylene was synthesized having 3-cyclopentadienylpropyldimethylsilyl end groups with a functionality near 2.0. While thermal extension at 80°C resulted in threefold molecular weight increase, coupling with bisdienophiles yielded greater than tenfold molecular weight increases. The retro-Diels–Alder reaction of coupled end groups prevents the attainment of high-molecular-weight polymers at equilibrium.

ω-Haloalkyl esters of 5′-adenosine monophosphate as potential active-site-directed reagents for dehydrogenases

A series of esters of adenosine 5′-monophosphate with ethyl, propyl, or hexyl moieties substituted at the ω-position with chlorine or bromine were prepared. The compounds were competitive inhibitors of horse liver alcohol dehydrogenase with respect to coenzyme, NAD +, and had inhibition (dissociation) constants in the range of 40 to 260 μ m at pH 8.0, 25 °C. The bromoalkyl esters were designed to be active-site-directed inactivators and were chemically reactive as tested with the model compound 4-( p-nitrobenzyl)pyridine. Yeast alcohol dehydrogenase was inactivated by the bromohexyl analog by an active-site-directed mechanism, with a K i = 1.5 mM and a pseudo-bimolecular rate constant of 0.03 m −1 s −1, which is 150 times larger than the bimolecular rate constant for inactivation by 2-bromoethanol. However, the rates of inactivation of other dehydrogenases treated with 10 m m concentrations of these compounds were generally slower than with the simpler reagent, 2-bromoethanol. Thus, the reactive functional group attached to the AMP moiety may not be properly oriented for affinity labeling of these dehydrogenases. The bromoalkyl esters may be useful for inactivating other enzymes.

PULMONARY PROBLEMS ENCOUNTERED BY THE INFANT OF THE DRUG-DEPENDENT MOTHER

As analogs of cis-[Pt(piam)2(NH3)2]·2H2O (1, piam = pivalamidate), two kinds of platinum mononuclear complexes, cis-[Pt(piam)2(NH2C3H7)2]·H2O (2) and cis-[Pt(piam)2(NH2C4H9)2] (3), have been synthesized and characterized by single-crystal X-ray analyses. The square-planar complexes 2 and 3 contain propyl and butyl moieties, respectively, enhancing the hydrophobicity. Both compounds have non-coordinated oxygen atoms in the piam ligands that can bind to a second metal, such as the Cu2+ ion, to afford trinuclear Pt–Cu–Pt complexes. UV–Vis and electron paramagnetic resonance spectra of the reaction of 2 and 3 with the Cu2+ ion show that both compounds form dinuclear Pt–Cu complexes as intermediates.

Absorption, distribution and metabolism of propyl anthranilate

Analysis of the gut contents of rats killed at intervals after dosage with propyl anthranilate or anthranilic acid suggested that both acid and ester were absorbed rapidly; the chief site of absorption was the stomach. Not more than a trace of the ester was hydrolysed in the stomach but of the dosed ester detected in the small intestine (less than 7%) a considerable proportion, increasing with time after dosing was present as anthranilic acid. Measurement of the leveof of radioactivity in the blood after administratioon of 14C-labelled propan-1-ol, propyl anthranilate or anthranilic acid showed that the alcohol was abosorbed more rapidly than either the ester or acid. Unchanged propyl anthranilate was readily detected in the blood of rats dosed with the ester and some unhydrolysed ester was excreted in the urine. The level of radioactivity of the organs of rats 2 h and 4 h after administration of the 14C-labelled compounds was measured. Velocity constants for the excretion of 14CO 2 by rats dosed with 14C-labelled propyl anthranilate were significantly lower than those found for rats dosed with [ 14C]propan-1-ol indicating a limiting step in the metabolism of the propyl moiety of the ester which did not occur in the metabolism of propan-1-ol. The urinary metabolites of anthranilic acid excreted by rabbits and rats dosed with the acid were qualitatively the same as those excreted by these species after dosing with propyl anthranilate; some quantitative differences were however, observed.

GC Analysis of Fatty Acid Composition of the Oil Containing Short Chain Fatty Acids

GC analysis of the fatty acid composition of the oils containing short chain fatty acids has not been performed satisfactorily because of the loss of short chain methyl esters during the ester preparation procedure. The loss was supposed to be due to volatility and water solubility of these esters. The authors have worked on the simple and quantitative procedure for the preparation of esters from the oils containing short chain acids. It was confirmed that the loss of short chain esters could be avoided by preparing propyl esters with BF3-1-propanol reagent and washing the ester solution with 10.5% aqueous sodium chloride. Then the propyl esters prepared from the standard mixture containing from butyric to octadecanoic acids were analyzed by GC. The propyl esters were prepared by following procedure. Five tenths grams of the oil containing short chain fatty acids and 6 ml of 0.5 N sodium hydroxide in 1-propanol were introduced into an 100 ml flask. Then the mixture was refluxed about 10 min. Seven ml of 14% BF3 1-propanol reagent was added through the condenser and refluxed for 10 min. Then 5 ml of heptane was added and boiled for 1 min. After cooling to room temperature 100 ml of 10.5% aqueous sodium chloride was added to the flask, and the flask was shaken for 1 min. The heptane layer was transfered into a test tube and the aqueous solution was reextracted by 5 ml of heptane. The heptane solutions were combined and used as the sample for GC. It was found that the response of propyl ester in FID increased as the carbon number of fatty acid increased, although the rate of increase was not so large as that of methyl ester. So GC analytical value (area percent) must be corrected using the correction factor obtained through the analysis of standard mixture. Moreover, the corrected analytical value should be converted to the fatty acid composition, since the ratio of propyl moiety in the propyl ester does not respresent the fatty acid composition. The propyl and methyl esters of fatty acids were prepared from milk fat and fatty acid compositions were analyzed by GC.

Activity of 0-Ethyl S-Propyl Organophosphoros Compounds Against Tobacco Budworms and Boll Weevils1234

In the laboratory, sprays of organophosphorus compounds with the O -ethyl S -propyl moieties were 5–100X more active against a susceptible strain of the tobacco budworm, Heliothis virescens (F.), and all except ER-9700, 9362, 9306, and NTN-9306 were 2–3X more active against the boll weevil, Anthanomus grandis Boheman, than certain alkyl or aryl O, O -dialkyl organophosphorus compounds. LD50’S for topical applications of Bay NTN-9306, ( O -ethyl 0 -[4-(methylthio)phenyl] S -propyl phosphorodithioate) to a susceptible and a field-collected strain of the tobacco budworm differed ca. 8X (0.024 and 0.19 mg/g after 48 h, respectively); this might indicate a potential for resistance to this new class of organophosphorus compounds. In the field, NTN-9306, Rohm & Haas RH-218 ( O -ethyl S -propyl O -(2,4,6-trichlorophenyl) phosphorothioate), and Ciba-Geigy CGA-15324 ( O -(4-bromo-2-chlorophenyl) O -ethyl S -propyl phosphorothioate), each applied at a rate of 1 lb/acre, reduced damage to bolls by Heliothis spp. (predominately the tobacco budworms) 81–85% compared with bolls in untreated plots.

Method for synthesis of quaternary ammonium salts

Quaternary ammonium salts that contain the allyl moiety are easily hydrogenated on palladium catalysts to the corresponding quaternary salts, which contain the propyl moiety.