Oxyacetic Acid Research Articles

Iodine-125-labeled 8-phenylxanthine derivatives: antagonist radioligands for adenosine A1 receptors

A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 adenosine receptors of bovine and rat brain and A2 receptors of human platelets was examined. The addition of arylamine or photosensitive aryl azide groups to the 3-position of xanthine had little effect on A1 binding affinity with or without iodination, whereas substitutions at the 1-position caused greatly reduced A1 binding affinity. The addition of an aminobenzyl group to the 3-position of the xanthine had little effect on A2 binding affinity, but 3-aminophenethyl substitution decreased A2 binding affinity. Two acidic 3-(arylamino)-8-phenylxanthine derivatives were labeled with 125I and evaluated as A1 receptor radioligands. The new radioligands bound to A1 receptors with KD values of 1-1.25 nM. Specific binding represented over 80% of total binding. High concentrations of NaCl or other salts increased the binding affinity of acidic but not neutral antagonists, suggesting that interactions between ionized xanthines and receptors may be affected significantly by changes in ionic strength. On the basis of binding studies with these antagonists and isotope dilution with the agonist [125I]N6-(4-amino-3-iodobenzyl)adenosine, multiple agonist affinity states of A1 receptors have been identified.

ChemInform Abstract: Synthesis via Sigmatropic Rearrangements. Part 13. An Unusual Cyclization of a Homoallyl Oxyacetic Acid Dianion.

AbstractStarting with (‐)‐carvone (I), the homoallylic oxyacetic acid (VI) is synthesized as shown in the reaction scheme.

Univalent Metal Complexes of (Perfluorophenoxy)acetic Acid. The Crystal Structures of (2,3,4,5,6-Pentafluorophenoxy)acetic Acid, Bis-μ-[(2,3,4,5,6-pentafluorophenoxy)acetato-O,O']-bissilver(I) and catena-Bis-μ-[(2,3,4,5,6-Pentafluorophenoxy)acetato-O]-bismercury(I)

The crystal structures of perfluorophenoxyacetic acid [(2,3,4,5,6- pentafluorophenoxy )acetic acid] and its anhydrous complexes with silver(I) and mercury(I) have been determined by X-ray diffraction and refined to residuals R = 0.046, 0.042 and 0.104 for 1235, 1789 and 2750 observed reflections respectively. The acid forms the usual hydrogen- bonded cyclic dimers [O---O, 2.705(3)Ǻ] with the oxyacetic acid side- chain synclinally oriented. Crystals age triclinic, space group Pī with Z 2 in a cell of dimensions a 7.479(1), b 7.592(2), c 8.463(2)Ǻ,α 80.15(2),β 85.34(2),γ 61.31(1)Ǻ. The silver complex, [Ag2L2],(1), has crystals with a 5.992(3), b 30.22(2), c 5.277(2)Ǻ, β 106.42(5)°, space group P21/a and Z 2. The bis-carboxylato (O,O′) dimers have Ag-Ag 2.943(1)Ǻ with Ag-O, 2.203, 2.230(3)Ǻ and O-Ag-O 161.6(2)°. The complex with mercury(I), [Hg2L2]n, (2), is centrosymmetric with the usual linear O-Hg-Hg-O-bonds [Hg-Hg, 2.514(1)Ǻ; Hg-O, 2.13(1)Ǻ; O-Hg-Hg, 173.9(2)°]. Longer peripheral bonds to Hg [Hg-O, 2.63(1)Ǻ] produce a polymeric structure. Crystals of (2) are triclinic, space group Pī with Z 1 in a cell of dimensions a 5.038(1), b 5.970(1), c 15.774(6)Ǻ, α 80.77(2),β 86.42(2),γ 84.38(2)°.

Synthesis via sigmatropic rearrangement. 13. An unusual cyclization of a homoallyl oxyacetic acid dianion

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis via sigmatropic rearrangement. 13. An unusual cyclization of a homoallyl oxyacetic acid dianionStanley Raucher, Linda M. Gustavson, and Ronald E. StenkampCite this: J. Org. Chem. 1987, 52, 13, 2760–2762Publication Date (Print):June 1, 1987Publication History Published online1 May 2002Published inissue 1 June 1987https://doi.org/10.1021/jo00389a022RIGHTS & PERMISSIONSArticle Views197Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (414 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Physiological activity spectra of existing graminicides and the new herbicide 2‐(2‐benzothiazolyl‐oxy)‐N‐methyl‐N‐phenylacetamide (mefenacet)

Summaryinhibitory activities of existing graminicides on root regeneration from monocotyledonous (oat) and dicotyledonous (soybean) plant cuttings in the light, in the dark and on algal growth were compared with the respective inhibitory activities of the new herbicide 2‐(2‐benzothiazo‐lyl‐oxy)‐N‐methyl‐N‐phenylacetamide (mefenacet). The mefenacet activity spectrum resembled that of the α‐chloroacetamide herbicides. Herbicide groups of other structure‐activity can be distinguished by their distinct activity spectrum. The mono‐oxygenase inhibitors piperonyl but‐oxide (PBO) and 1‐aminobenzotriazole (ABT) were found to antagonize the inhibitory activities of herbicides from the thiolcarbamate, α‐chloroacetamide, and oxyacetic acid amide structure groups in the oat rooting and leaf growth tests. The critical evaluation of the presently available information on graminicide and safener mode of action suggests the concept that lipid biosynthesis on the physiological level and mono‐oxygenase type enzymes on the biochemical level may hold the target sites for many of the graminicides and safeners discussed.

Suitability of hardwoods treated with phenoxy and pyridine herbicides for use as firewood.

Potential exposure to pesticide residues resulting from burning wood treated with phenoxy and pyridine herbicides was assessed. Wood samples from trees treated with 2,4-D [2,4-dichlorophenoxy acetic acid], dicamba [3,6-dichloro-o-anisic acid], dichlorprop [2-(2,4-dichlorphenoxy) propionic acid], picloram [4-amino-3,5,6-trichloropicolinic acid], and triclopyr (3,5,6-trichloro-2-pyri dinyl)oxy acetic acid contained variable amounts of parent compound residues at 4, 8, and 12 months after application. At the time of the latter sampling, residues of 2,4-D, dicamba, and picloram were <2.1 mg/kg on a fresh weight basis. Mean residue concentrations of triclopyr and dichlorprop were somewhat higher at 3.5 and 13.0 mg/kg, respectively. In a laboratory experiment, samples with known amounts of herbicide residue were subjected to either slow or rapidly burning conditions in a tube furnace. During slow combustion, relatively stable compounds such as 2,4-D, dicamba, and dichlorprop were released in significant amounts. Rapid combustion greatly enhanced decomposition of 2,4-D, dicamba, dichlorprop, picloram, and triclopyr. A well-developed fire in a wood stove or fireplace, with active flaming combustion, where temperatures commonly reach 800–l,000°C, should result in greater than 95% thermal decomposition of the herbicides examined in this study. Burning of herbicide-treated wood under smoldering conditions could result in very low levels of herbicide residue in ambient indoor air. However, the exposure levels are less than 0.3% of the threshold limit value for 2,4-D and triclopyr. The exposure is also more than 3 orders of magnitude lower than the established acceptable daily intakes for these products.

Lack of Neuropathologic Consequences of Repeated Dermal Exposure to 2,4-Dichlorophenoxyacetic Acid in Rats

Lack of Neuropathologic Consequences of Repeated Dermal Exposure to 2,4-Dichlorophen- oxyacetic Acid in Rats. MATTSSON, J. L., JOHNSON, K. A., AND ALBEE, R. R. (1986). Fundam. Appl. Toxicol. 6, 175–181. A 24% aqueous solution of the dimethylamine salt of 2,4-dichioro-phenoxyacetic acid (2,4-D amine) was applied to the legs of male Fischer 344 rats 2 hr/day, 5 days/week, for 2 weeks. Because this concentration caused severe skin lesions, a second group of rats was treated similarly with a 12% solution of 2,4-D amine for 3 weeks. The 12% solution caused only mild skin changes. The plasma 2,4-D content, at the end of exposure, was nearly five times greater in the rats exposed to the 24% solution than to the 12% solution (323 vs 66.5 μg/ml). The severe skin changes probably facilitated absorption in the rats treated with the 24% solution. Rats treated with either concentration weighed less than controls. Although histologically normal, kidneys of treated rats weighed more than controls. The increased kidney weights were attributed to physiological adaptation due to active excretion of absorbed 2,4-D. Light microscopic examination of tissues, other than skin, revealed no differences between treated and control animals. There were no nervous system pathologic changes although the rats were exposed to sufficient amounts of 2,4-D amine to cause severe skin lesions, decreased body weights, and increased kidney weights.

Prolactin and milk ejection during the first 20 minutes of suckling in the rat: blockade by Nembutal and by amino oxyacetic acid.

Prolactin and milk ejection during the first 20 minutes of suckling in the rat: blockade by Nembutal and by amino oxyacetic acid.

Uptake, accumulation, and elimination of HCB and 2,4-D by the terrestrial slug, Deroceras reticulatum (Müller).

The earthworms, snails, slugs and other soil invertebrates are considered to be important components in food chain as they form a significant proportion ol the diet of other animals. Therefore, monitoring of these organisms for the source oi pesticide residues to other animals *eeding on them, and as well as for establishing the contamination levels of agricultural soils is an approach well documented (WHEATLEY & HARDMAN, 1968; DAVIS, 1968; DAVIS & FRENCH, 1969; GISH, 1970; EDWARDS & THOMPSON, 1973; KUHR et al., 1974; BEYER & GISH, 1980; YADAV et al., 1981). Amongst these organisms, terrestrial slugs and snails appear to be relatively resistant to pesticides but have the capacity to accumulate organochlorine (STRINGER & PICKARD, 1965; GISH, 1970; DINDAL & WURZINGER, 1971; KUHR et al., 1974) and organophosphorus insecticide residues (EDWARDS, 1976) in their body tissues. Since slugs in their natural habitates are in direct contact with the soil and the vegetation, they are therefore exposed to the pesticides applied in the field and to other xenobiotics in the environment. It is not yet clear as to which route(s) pesticides get entry into the slugs body, and whether there are any diiferences in the quantities oi the residues taken up from different sources and in the retention of these residues if there are more than one route of intake. To understand more about the behaviour of slugs we studied the uptake of two test pesticides, namely [14C]-hexachloro benzene (HCB) and [14C]2,4-dichlorophen oxyacetic acid (2,#-D); (i) by ieeding the slugs via carrot discs daily for a period of five to ten days, and (ii) exposing the Mugs continuously to the contaminated soil. HCB was chosen for its persistent and lipophilic property, and 2,#-D for its polarity and hydrophilic property. With this preliminary approach it was possible to determine the excretion rates and retention of HCB and 2,4-D residues and their metabolites in slug tissues upon ingestion and exposure.

A novel bioassay for herbicides used in wild oat control and for the assessment of their interactions with other xenobiotics

SUMMARYA bioassay is described which uses young oat seedlings to determine the activity of wild oat herbicides alone and in mixtures with other xenobiotics.Test solution (10 μl) was pipetted into the first leaf sheath of the oat seedlings, and 24 to 48 h later, basal shoot sections were removed and cultured for 24 h on agar. The inhibition of leaf growth from these sections, compared with control sections, was an assessment of herbicidal activity. Marked inhibition occurred when as little as 0–5 to 1 ‐0 μg of either diclofop‐methyl or diclofop had been applied to each plant. Wheat and barley seedlings were unaffected by 12 μg of these herbicides, reflecting their known selectivity in cereal crops.The assay was used to evaluate the antagonisms of diclofop‐methyl and diclofop activity by 2,4‐D, MCPA, 2,3,6‐TBA and also related ‘non‐auxins’ (3,5‐dichloro‐phenoxyacetic acid and 2,3,5‐TIBA). Diclofop‐methyl was compatible with the 1‐methylheptyl ester of (4‐amino‐3,5‐dichloro‐6‐fluoro‐2‐pyridyl)oxyacetic acid (Dowco 433).The test allows the simultaneous examination of herbicidal responses and related metabolic changes in the oat tissue. As the procedure uses small amounts of chemical, it is suitable for 14C tracer studies and other investigations for v/hich research chemicals are not freely available. The use of the test with other species and other herbicides is discussed, and possible applications for screening for crop safeners and investigations on crop tolerance are suggested.

Amino acid cycling in ribbed mussel tissues subjected to hyperosmotic shock

AbstractVariations in the high concentrations of intracellular amino acids in the tissues of osmoconforming, euryhaline animals such as the ribbed mussel (Modiolus demissus) appear to have a major role in adjusting intracellular osmotic pressure in response to extracellular osmotic change. The experiments discussed here on the metabolic origins and fates of these amino acids are part of a continuing study on the physiological mechanisms regulating the concentrations of these amino acids. Tissues isolated from ribbed mussels adapted at 12 o/oo were incubated for 8 hrs. in artificial seawater media at 12 o/oo or 32 o/oo. The total marked increase in total intracellular amino acid levels at 32 o/oo vs. 12 o/oo was not blocked by addition of 1 mM amino oxyacetic acid (AOA). However, with AOA the usual increase in alanine and proline concentrations was offset by increases in a variety of amino acids including ornithine. AOA inhibited transaminases associated with ornithine, alanine, and glutamate metabolism (I50s:10−8 to 10−5 M) but did not inhibit the L‐amino acid oxidase. 14C‐tracer experiments with isolated gill tissue indicated no synthesis of proline from glutamate and enhanced synthesis of proline, alanine, and glutamate from ornithine and arginine at 32 o/oo vs. 12 o/oo. L‐amino acid oxidase, proline oxidase, glutamate dehydrogenase, and enzymes in the metabolic pathway between arginine and proline were found in cell‐free extracts of gill tissue. During hyperosmotic stress, proline was apparently derived from the phosphoarginine‐arginine pool, whereas alanine and the other accumlating amino acids have multiple metabolic origins including the amino acids released during protein turnover, the metabolites of the phosphoarginine pool, and possibly endogenous carbohydrate.

Iminyls. Part 8. Intramolecular addition to nitrile groups

Evidence for the radical polymerisation of nitrile groups in polyacrylonitrile has been sought using model compounds. No evidence for the cycloaddition of iminyls to nitrile groups has been obtained but nucleophilic addition occurred easily. Thus, 1,8-dicyanonaphthalene reacted with hydroxylamine to give naphthalimide dioxime and with butyl-lithium to give azaphenalene derivatives but adamantyl radicals did not attack the nitrile functions.3-Benzoyl-1,5-dimethylpimelonitrile and hydroxylamine yielded a piperidine and two decahydro-1,8-naphthyridine derivatives instead of the expected oxime. Reaction of the piperidine with bromoacetic acid gave an oxyacetic acid which was converted by persulphate oxidation into a cis-trans mixture of azopyridines. The structure of one of the decanaphthyridines has been established by X-ray crystallographic analysis.

The metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-cyanopyridine in rats, dogs, and humans.

Studies of the metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-[14C]cyanopyridine (I) have been performed in humans, dogs, and spontaneously hypertensive rats. After an iv injection of I (5 mg/kg), a substantial fraction of the radioactivity was excreted in the feces of rats (32%) and dogs (31%). After oral administration of I (5 mg/kg) the urinary recoveries of radioactivity for rat and dog were 19% and 53%, respectively, and represented a minimum value for absorption because of biliary excretion of radioactivity. In man, bililary excretion of I appeared to be of minor significance because four male subjects, after receiving 6 mg of I p.o., excreted 76% and 9% of the dose of radioactivity in the urine and feces, respectively. Unchanged I represented 58% of the radioactivity excreted in human urine. The half-life for renal elimination of I was determined to be 4.0 +/- 0.9 /hr. In contrast, unchanged I represented 7% and 1% of excreted radioactivity in rat and dog urine, respectively. A metabolite of I common to man, dog, and rat was identified as 5-hydroxy-I, which represented approximately 5% of the excreted radioactivity in all species. Minor metabolites of I in which the pyridine nucleus had undergone additional hydroxylation were present in dog urine along with an oxyacetic acid metabolite, also bearing a hydroxylated pyridine nucleus.

Effect of GABA agonists and modulators on prolactin release

Administration of GABA agonists has been found both to stimulate and inhibit prolactin secretion in vivo. These independent actions represent a stimulatory effect after intracerebroventricular injection mediated by an action within the CNS and an inhibitory response resulting from a direct action of GABA on the pituitary cell membrane to reduce prolactin release. Thus the response to exogenously administered GABA or its agonists depends on the route of injection. In this study amino oxyacetic acid and isonicotinic acid hydrazide were given to increase or decrease respectively the concentration of endogenous GABA. Benzodiazepine was used to enhance the affinity of the receptor for endogenous GABA. Unlike the agonists used previously these drugs enter the CNS after systemic administration and can thus produce two opposing effects. The results indicated that increased blood and brain GABA content or receptor affinity was associated with reduced prolactin release. These effects however were more significant when basal prolactin secretion was stimulated by estrogen or haloperidol.

SPECIES DIFFERENCES IN THE BINDING OF COMPOUNDS DESIGNED TO FIT A SITE OF KNOWN STRUCTURE IN ADULT HUMAN HAEMOGLOBIN

1. Oxygen dissociation curves are reported for human haemoglobins A1, FII, FI, A1c and Raleigh (beta1 valine leads to acetylalanine) and for horse haemoglobin in the absence and presence of 2,3-diphosphoglycerate (DPG), or 4,4'-diformyl-2-bibenzyl oxyacetic acid, or the bisulphite addition compound of the latter. 2. These haemoglobins were selected because their amino acid sequences are different at the DPG receptor site of human adult deoxyhaemoglobin. 3. The size of the shifts of the dissociation curves are in the sequence expected from the postulated numbers of interactions made by each compound with each haemoglobin type, based on the assumption of a common receptor site for the three compounds. 4. Multiple linear regression analysis shows that the free energies of interaction of the compounds with the haemoglobins may be predicted, to a first approximation, by summing the number of ionic and covalent bonds predicted for each effector-receptor combination, a reversible covalent bond contributing about twice as much energy (-6.78 kJmol-1) as an ionic interaction (-3.14 kJmol-1).

Effect of mercaptopicolinic acid and of transaminase inhibitors on glycogen synthesis by rat hepatocytes

To explore the mechanism of the stimulation of glycogen synthesis by amino acids (1) we have studied the effects of transaminase inhibitors and of mercaptopicolinic acid, (MPA) an inhibitor of phosphoenol pyruvate carboxykinase. Mercaptopicolinic acid enhanced glycogen synthesis from fructose, dihydroxyacetone and xylitol. Stimulation of glycogen synthesis with hepatocytes from fasted rats by 0.5 mM mercaptopicolinic acid was 50–70% as effective as 10 mM glutamine. With hepatocytes from fed rats, the stimulation of glycogen synthesis by mercaptopicolinic acid was more pronounced, and stimulation by mercaptopicolinic acid and amino acids was additive. Glycogen synthesis as high as 1% in wet weight per hour was attained in hepatocytes with a high initial glycogen content. Over 80% of glycogen synthase was in the active (a) form. Amino oxyacetic acid greatly depressed or abolished the stimulatory effect of glutamine and asparagine and of mercatopicolinic acid, and induced extensive glycogen breakdown in hepatocytes of fed rats.

A 1,3-hydride shift in the rearrangement of (1-phenylallyl)oxyacetic acid to 2-ethyl-2-phenyl-1,3-dioxolan-4-one

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA 1,3-hydride shift in the rearrangement of (1-phenylallyl)oxyacetic acid to 2-ethyl-2-phenyl-1,3-dioxolan-4-oneMarcel K. Eberle and Gerard G. KahleCite this: J. Am. Chem. Soc. 1977, 99, 18, 6038–6042Publication Date (Print):August 1, 1977Publication History Published online1 May 2002Published inissue 1 August 1977https://doi.org/10.1021/ja00460a032RIGHTS & PERMISSIONSArticle Views596Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (674 KB) Get e-Alerts Get e-Alerts

γ-Aminobutyric Acid: Possible Role as a Neuro-Ophthalmic Modulator

We report for the first time that depletion of endogenous sources of retinal GABA by the hydrazine compound semicarbazide results in the stimulation of the rate and intensity of impulse transmission along the visual pathway. This effect was 50% more pronounced when ophthalmic drops were used in place of direct cortical administration. Depletion of retinal GABA resulted in the potentiation of the intensity of the photo-induced excitatory postsynaptic potentials arriving at the optic cortex. These effects of semicarbazide were antagonized by pretreatment with the GABA-T inhibitor amino oxyacetic acid and by GABA. We have hypothesized that GABA is probably a compensatory modulator of visual functions. The efficacy of a new route for the study of GABA in vivo and the possible clinical application of this modality have been demonstrated.

Regulation of methionine transport activity in Escherichia coli.

Methionine transport activity in cells of Escherichia coli K-12 is regulated by the level of the internal methionine pool. Transport activity is depressed either in cells grown in the presence of methionine or in cells exposed to methionine immediately prior to harvest. Alpha-Keto-gamma-methiol-butyrate, D-methionine, or methionine sulfoxide have little effect on the initial rate of uptake of L-methionine when they are added simultaneously with the substrate. However, methionine transport is markedly reduced in cells exposed to these sources of L-methionine before the addition of substrate. This reduction is prevented if the cells are treated with amino oxyacetic acid. The initial rate of uptake into L-methionine-loaded cells was lower than that into unloaded cells. This inhibition affected both methionine transport systems and the inhibition by the internal pool appeared to be non-competitive with the external methionine concentration. Two classes of mutants with increased methionine pools have decreased rates of uptake. Conversely, starvation for methionine in a methionine auxotroph with high rates of methionine degradation resulted in a substantial increase in the rate of methionine transport. Thus, these transport systems are subject to regulation by the internal pool size and possibly by repression.

Synthesis of 4-pyridoxyacetic acid via a pyridine N-oxide derivative.

4-Pyridoxyacetic acid, a substance to be used in a study on plant growth substances, cannot be obtained by reacting 4-hydroxypyridine with chloroacetic acid or ethyl diazoacetate, only the N-(4-pyridonyl) acetate or its ester being formed. The desired compound was synthesized from 4-hydroxypyridine 1-oxide by converting the N-oxide with chloroacetic acid into N-(4-pyridonyl) oxyacetic acid and by heating this acid with a solution of ethyl diazoacetate in petroleum ether. Discussion is made on the mechanism of this process by other routes used for its preparation.