PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Azabicyclo Compounds”

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 721 records · Page 40Linked to original sources
PubMed1992

5-hydroxytryptamine4 receptor agonists facilitate cholinergic transmission in the circular muscle of guinea pig ileum: antagonism by tropisetron and DAU 6285.

The effect of 5-hydroxytryptamine (5-HT), BIMU 8 (endo-N-(8-methyl-8-azabicyclo [3.2.1.] oct-3-yl)-2,3-dihydro-3-(1-methyl)ethyl-2-oxo-1H-benzimidazole-1- carboxamide hydrochloride) and cisapride was studied on the electrically-induced neurogenic cholinergic twitch contractions in the guinea pig ileum circular muscle. These compounds caused a concentration-dependent increase in the amplitude of submaximal twitch contractions with the following rank order of potency: 5-HT greater than BIMU 8 = cisapride. The effect of 5-HT was competitively antagonized by tropisetron (ICS 205-930) (apparent pA2 value: 6.4), suggesting an interaction at 5-hydroxytryptamine4 (5-HT4) receptors. The novel benzimidazolone derivative DAU 6285 (endo-6-methoxy-8-methyl-8-azabicyclo [3.2.1.] oct-3-yl-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate hydrochloride), antagonized the effect of 5-HT, BIMU 8 and cisapride with apparent pA2 values in the range 7.1-7.3. Our findings demonstrate that cholinergic neurones innervating the circular coat are endowed with excitatory 5-HT4 receptors. DAU 6285 is approximately 5-9-fold more potent than tropisetron as antagonist at these receptors.

Animals↗
PubMed1987

Quantitation of ceftetrame in human plasma and urine by high-performance liquid chromatography.

A method is described for quantifying ceftetrame, the acid metabolite of methylene (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- [(5-methyl-2H-tetrazol-2-yl)-methyl]-8-oxo-5-thia-1-azabicyclo[4.2 .0]oct-2-ene-2-carboxylate pivalate, an orally active cephalosporin. Sodium benzylpenicillin is added to the plasma as the reference standard. The compounds are extracted from plasma or urine using a Bond Elut phenyl column. An aliquot of the methanol eluate is analyzed by high-performance liquid chromatography using a Waters Nova-Pak phenyl column and a UV detector set to 225 nm. The ratios of the peak heights for ceftetrame and sodium benzylpenicillin are calculated and converted to concentrations of analyte with calibration curves that are generated from the analysis of analyte-free plasma or urine fortified with various amounts of ceftetrame and a fixed amount of sodium benzylpenicillin. For plasma, the limit of quantitation for the assay is 0.48 microgram/ml and the inter-assay precision (relative standard deviation) is 9.3%. For urine, the limit of quantitation for the assay is 19.1 micrograms/ml, and the inter-assay precision is 4.9%.

Adult↗
PubMed1988

High-performance liquid chromatographic determination of a new beta-lactamase inhibitor and its metabolite in combination therapy with piperacillin in biological materials.

[2S-(2 alpha,3 beta,5 alpha)]-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-yl- methyl)-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylic acid 4,4-dioxide (YTR-830H) is a new beta-lactamase inhibitor and the combination therapy of this compound with piperacillin is now under study. For the determination of the beta-lactamase inhibitor and piperacillin in biological materials, plasma and visceral tissue homogenates were deproteinized, whereas diluted urine and filtered faeces homogenates were treated with a Sep-Pak C18 cartridge. In order to assay the inactive metabolite of beta-lactamase inhibitor, each sample was treated with a Sep-Pak C18 cartridge. Aliquots of each preparation were chromatographed using ion-pair and reversed-phase chromatographic techniques on a high-performance liquid chromatograph equipped with a UV detector, set at 220 nm. The detection limits of beta-lactamase inhibitor and piperacillin were 0.2 microgram/ml in plasma, 2.5-5.0 micrograms/ml in urine and 0.2-0.5 microgram/g in visceral tissue and faeces. Those of the metabolite were 1.0 microgram/ml in plasma, 2.5-5.0 micrograms/ml in urine and 1.0 microgram/g in visceral tissue and faeces. A precise and sensitive assay for the determination of the beta-lactamase inhibitor, its metabolite and piperacillin is described, and their stabilities in several media are reported.

Animals↗
PubMed2006

N-substituted 4beta-methyl-5-(3-hydroxyphenyl)-7alpha-amidomorphans are potent, selective kappa opioid receptor antagonists.

In a previous study, we identified (-)-N-[(1R,4S,5S,7R)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl]-3-(1-piperidinyl)propanamide (5a, KAA-1) as the first potent and selective kappa opioid receptor antagonist from the 5-(3-hydroxyphenyl)morphan class of opioids. In this study we report an improved synthesis of this class of compounds. The new synthetic method was used to prepare analogues 5b-r where the morphan N-substituent and 7alpha-amido group were varied. Most of the analogues showed sub-nanomolar potency for the kappa opioid receptor and were highly selective relative to the mu and delta opioid receptors. (-)-3-(3,4-Dihydroisoquinolin-2(1H)-yl)-N-{(1R,4S,5S,7R)-5-(3-hydroxyphenyl)-4-methyl-2-[2-(2-methylphenyl)ethyl]-2-azabicyclo[3.3.1]non-7-yl}propanamide (5n, MTHQ) is at least as potent and selective as nor-BNI as a kappa opioid receptor antagonist in the [35S]GTP-gamma-S in vitro functional test.

Animals↗
PubMed1992

Structural analysis of non-volatile compounds by liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry: thermal isomerization of benzylpenicillin in a Plasmaspray interface.

Isomerization and degradation of benzylpenicillin ((2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid) were studied using a combination of Plasmaspray (PSP) liquid chromatography/tandem mass spectrometry (LC/MS/MS) and liquid secondary ion tandem mass spectrometry (LSI MS/MS). Benzylpenicillin was isomerized to benzylpenicillenic acid (3-mercapto-N-[[5-oxo-2-(phenylmethyl)-4(5H)- oxazolylidene]methyl]valine) in the PSP interface/ion source. The isomerization was inferred from the probe temperature dependence of PSP LC tandem mass spectra and discrepancies in the daughter ions between PSP LC and LSI tandem mass spectra. High temperature at the PSP interface was responsible for the isomerization, since the difference between PSP LC and LSI tandem mass spectra became smaller as the probe temperature was lowered. It was also found that benzylpenicillin was decomposed to benzylpenilloic acid (5,5-dimethyl-2-[(phenylacetamido)methyl]thiazolidine-4-carboxylic acid), N-(phenylacetyl)glycine, N-(phenylacetyl)glycinal and 3-mercaptovaline in the PSP interface/ion source. The degradation products formed in the interface/ion source were identical to those formed in acidic solution. The results show that degradation of penicillins can be investigated by PSP LC/MS and PSP LC/MS/MS.

Chromatography, Liquid↗
PubMed2004

Synthesis and antibacterial activity of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position.

A series of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position were synthesized to obtain potent drugs for the treatment of Gram-positive infections. Some compounds exhibited excellent antibacterial activity, and potent inhibitory activity against bacterial DNA topoisomerase IV. In addition, some of the potent compounds showed reduced inhibitory activity against human DNA topoisomerase II compared with the corresponding noncyclopropane-fused compounds.

Anti-Infective Agents↗
PubMed2005

Electronic structure effects of amide group: Vince lactam.

HeI photoelectron spectrum of 2-azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam) has been measured. The assignment of the spectrum was made by comparison with photoelectron spectra of related compounds and by taking into account the lactam's molecular structure. The analysis of the electronic structure of amide group, in terms of inductive and conjugative effects, is presented on the basis of photoelectron spectroscopic data.

Amides↗
PubMed2006

Bicyclic glutamic acid derivatives.

For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

Amino Acids, Cyclic↗
PubMed2006

From macrocycle dipeptide lactams to azabicyclo[X.Y.0]alkanone amino acids: a transannular cyclization route for peptide mimic synthesis.

[reaction: see text] Macrocyclic and fused bicyclic dipeptides are complementary motifs for mimicry of different types of beta-turn geometry. Macrocyclic dipeptide mimics have served as precursors for the synthesis of their bicyclic counterparts using electrophilic transannular cyclizations of 9- and 10-membered ring lactams 9-12 to form azabicyclo[4.3.0]- and -[5.3.0]alkanone amino esters 13-16.

Amino Acids↗
PubMed1992

Characterization of the binding of a potent, selective, radioiodinated antagonist to the human neurokinin-1 receptor.

We have synthesized a potent, selective, radioiodinated antagonist of the human neurokinin-1 (NK1) receptor and have characterized its binding to the cloned receptor expressed in Chinese hamster ovary cells. (cis)-2-(Diphenylmethyl)-N-[(2-iodophenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (L-703606) inhibits binding of 125I-Tyr8-substance P to the human NK1 receptor with an IC50 of 2 nM. This compound is a competitive antagonist of substance P-induced inositol phosphate generation, with a Kb of 29 nM. [125I]L-703606 binds to a single class of high affinity binding sites in human NK1/Chinese hamster ovary cell membranes (Kd = 0.3 nM). Substance P inhibits the binding of [125I]L-703606 to 65% of the NK1 receptor sites with a Kd of 0.04 +/- 0.03 nM and to the remaining 35% of the sites with a Kd of 1.5 +/- 0.7 nM. Addition of the nonhydrolyzable GTP analog guanylyl-5'-(beta, gamma-imido)diphosphate [Gpp(NH)p] shifts greater than 90% of the binding sites to the lower affinity state. In addition, Gpp(NH)p markedly alters the dissociation of substance P from the NK1 receptor by increasing the number of sites in the low affinity, rapidly dissociating state. However, Gpp(NH)p does not affect the rate of dissociation of [125I]L-703606. These data suggest that the pharmacological properties of [125I]L-703606 binding to the human NK1 receptor are similar to those of antagonists of nonpeptide guanine nucleotide-binding protein-coupled receptors and that this ligand will be useful for the biochemical and pharmacological characterization of the human NK1 receptor.

Amino Acid Sequence↗
PubMed1984

Determination of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) and its hydrolysis product in serum and urine.

A highly sensitive and specific enzymatic assay for the quantitative determination of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) and its hydrolysis product Hoe 498-diacid in serum and a GLC method for the simultaneous determination of both compounds in urine are described. Both methods involve extraction from the respective biological fluid using disposable C 18 columns. In serum, the enzyme-inhibiting properties of Hoe 498-diacid (Hoe 498 can readily be converted to its hydrolysis product) are utilized for the determination of both compounds concurrently. The serum extract is dissolved in buffer solution and incubated with human serum as angiotensin converting enzyme (peptidyl-dipeptide-hydrolase, EC 3.4.15.1) source and hip-his-leu substrate. The hippuric acid liberated is quantitated by HPLC. The urine extract is treated with diazomethane followed by trifluoroacetic anhydride to convert Hoe 498 and Hoe 498-diacid to their methylester, trifluoroacetyl derivatives, which are then determined simultaneously by GLC using a nitrogen specific detector.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Comparative stability of carbapenem and penem antibiotics to renal dehydropeptidase-I.

Comparison has been made on the stability of 4 carbapenems and 3 penems against porcine renal dehydropeptidase-I (DHP-I). Evaluated were the carbapenems (5R,6S)-3-[[2-(formimidoylamino)ethyl]thio]-6-[(R)-1-hydroxyethyl] - 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate, CAS 74431-23-5, in the following called FAC, (5R,6S)-3-[(S)-1-(acetimidoylpyrrolidin-3-yl)thio]-6-[(R)-1- hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid, CAS 87726-17-8, in the following called AHC, (4R,5S,6S)-3-[[(3S,5S)-5-dimethylcarbamoylpyrrolidin-3-yl]thio]-6- [(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2- carboxylic acid trihydrate, CAS 96036-03-2, in the following called DHC. (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a] [1,2,4]triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-ca rbapen - 2-em-3-carboxylate, in the following called DHM, and the penems (5R,6S)-6-[(R)-1-hydroxyethyl]-7-oxo-3-[(R)-2-tetrahydrofuryl]-4-thia-1 - azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid sodium salt, in the following called HTC, (5R,6S)-2-carbamoyloxymethyl-6-[(1R)-hydroxyethyl]-2-penem-3-carboxylic acid, in the following called CHC, (5R,6S)-6-[(R)-1-hydroxyethyl]-3-[(3S)-(cis-1-oxotetrahydrothiophen++ +-3-yl) thio]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, in the following called HHC. According to the comparison of the Vmax/Km ratios, the order of stability of the compounds to hydrolysis by renal DHP-I was as follows: DHM >> DHC > HHC > AHC > HTC > CHC > FAC. From this result it is particularly noteworthy that DHM has extremely high stability against renal DHP-I.

Animals↗
PubMed2001

Trishomocubanes: novel sigma-receptor ligands modulate amphetamine-stimulated [3H]dopamine release.

Several trishomocubane analogues of the type 4-azahexacyclo [5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane exhibited moderate to high affinity at sigma-receptor subtypes and low or negligible affinity at dopamine and serotonin transporters (SERT). Selected compounds were examined for their effects on amphetamine-stimulated [3H]dopamine release from striatal slices in vitro. Compounds 1, 2, 3 and 4 significantly enhanced amphetamine-stimulated release in a concentration-dependent manner. Compound 4, with the highest affinity and selectivity for the sigma(2)-receptor subtype, displayed the greatest potency. The enhancement produced by 1 and 2 was fully reversed by the selective sigma(2) antagonists 1'-[4-[1-(4-fluorophenyl)-1-H-indol-3-yl]-1-butyl]spiro[iso-benzofuran-1(3H), 4'piperidine] (Lu28-179), endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)ethyl-2-oxo-1-H-benzimidazole-1-carboxyamidehydrochloride (BIMU-8) and the non-subtype selective antagonist N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-pyrrolidinyl)ethylamine (BD1008). These data suggested a potential role for compounds 1 through 4 as sigma(2)-receptor agonists in functional studies. In addition, a D(3)-trishomocubane compound 5 displayed low affinity at sigma receptors (K(i)=3 microM) and moderate affinity at dopamine transporters (K(i)=623 nM). Compound 5 significantly inhibited the potentiation mediated by compound 2, presumably through sigma(2)-receptor antagonism, or a direct action on dopamine transporters.

Amphetamine↗