Biomedical subjects
Publications and source records attributed to A F Casy.
The mass spectrometric behaviour of nineteen diuretic agents in clinical use under conditions of 70 eV electron impact is analysed from reported and novel mass spectra. The molecular compositions of fragment ions are supported by high resolution data in selected cases, and a scheme presented for the rapid identification by MS of diuretics within the group.
The preparation and stereochemical characterization of (+/-)-1,trans 2,6-trimethyl-4-phenyl-4-propionoxypiperidine hydrochloride and its (+)- and (-)-antipodes are described. The absolute configurations of the antipodes were established by X-ray analysis of the corresponding (-)-4-piperidinol hydrobromide. In antinociceptive tests on mice and rats, the (+)-2S,6S ester proved the more potent antipode by factors of at least 10 (rats) and 20 (mice), a result consistent with earlier proposals made about the probable uptake conformation of pethidine reversed esters at opioid receptors.
The mass spectral features of four diastereoisomeric pairs of peptides related to the enkephalins recorded under fast-atom bombardment conditions are presented and shown to provide evidence of molecular weight and amino acid content and sequence.
The preparation and resolution of 1,3,3-trimethyl-4-phenyl-4-(propionyloxy)piperidine (5,3-methylprodine) are described, and the results of the antinociceptive activities of the products by hot-plate (mice) and tail-withdrawal (rats) tests are shown to support proposals made from a recent analysis of the stereochemical structure-activity relationships of C-methyl derivatives of the reversed ester of meperidine. Data of absolute configuration were obtained by X-ray crystallography of a hydrobromide salt.
NMR evidence of the temperature dependence of NH resonances and magnitudes of alpha-CH-NH couplings is advanced in support of preferred beta-bend conformations for five enkephalin-like pentapeptides as solutes in DMSO-d6. The relevance of these and related conformational studies to the interactions of peptides of the enkephalin class with opioid receptors is questioned.
The preparation and stereochemical characterization of phenolic analogues of the reversed ester of pethidine, alpha- and beta-prodine and a 1-phenethyl congener are described. All the compounds were weakly active or inactive as agonists in rodent antinociceptive tests and failed to antagonize fentanyl in rats. The results substantiate the view that the morphine and 4-phenylpiperidine groups of analgesics differ in their modes of interaction with opiate receptors, except possibly when the piperidine derivative carries a C-4 carbon substituent.
The spectral assignations of all the main resonances in the 13C nuclear magnetic resonance spectra in DMSO-d6 or D2O are presented and reviewed for ten of the principal tetracyclines in therapeutic use: tetracycline, chlortetracycline, 6-demethylchlortetracycline, minocycline, oxytetracycline, methacycline, meclocycline, doxycycline, rolitetracycline and lymecycline. NMR techniques employed include: proton noise-decoupled spectra, off-resonance decoupled spectra, nuclear Overhauser enhancement and the INEPT technique (insensitive nuclei enhanced by polarization transfer). 13C NMR is also examined as a means of detecting and identifying the principal degradation and isomerization products of tetracycline antibiotics. The analytical potential of 13C NMR is discussed with respect to quantitative analysis of impurities, studies on sites of protonation and metal-binding studies.
The binding and pharmacological profiles of some 4-anilinopiperidine and 4-phenylpiperidine analogues were determined. The potency of the compounds to displace the binding of selective tritiated ligands was measured in homogenates of guinea-pig brain at 25 degrees C. All the compounds tested had high affinity for the mu-binding site, low affinity for the delta-site and were almost inactive at the kappa-site. The compounds were also tested for agonist activity in the guinea-pig ileum and the vasa deferentia of the mouse and rat. The pharmacological and binding profiles were compared.
The 1H NMR spectra of seven tetracycline antibiotics of clinical importance are reported and assigned as solutes in DMSO-d6 and other solvents. The data are analysed in terms of analytical utility and the provision of evidence of solute stereochemistry.
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Two procedures for applying 13C n.m.r. spectroscopy to the quantitative analysis of the C1, C1a, and C2 components of gentamicin sulphate samples are described. One is based on the use of calibration plots of peak height ratios of analyte to standard (dioxan) resonance intensities recorded under conditions of full relaxation, the other upon a steady-state experiment and the use of weighting factors. Spectrometer operating conditions are discussed, and the need for measurement of longitudinal relaxation time (T1) data described. Results for seven commercial samples are given and comparisons made between the two n.m.r. methods and an h.p.l.c. procedure in terms of accuracy, specificity and convenience.
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Explore the source record for details and available documents.
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A number of N-substituted 2,3-dimethyl-3-arylpiperidines having an m- or p-arylhydroxyl were prepared and evaluated for analgesic agonist and antagonist properties. The diastereomeric N-allyl and N-cyclopropylmethyl derivatives behaved as pure potent antagoinists. Substitution of the arylhydroxyl from the meta to the para position resulted in a net fall of the antagoinist activity.
The preparation of three isomeric 1-tetralone hydrozones 4 and three isomeric 1-indanone hydrozones 5 possessing a single quaternary ammonium center is described. Several of the compounds possessed significant neuromuscular blocking activity, and two approached suxamethonium in potency. 1H NMR evidence obtained from a study of the N,N-dimethylhydrozones indicated that the hydrazones adopted an E configuration in solution.
The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me, c-6-Me, r-4-OCOMe isomer was an effective analgesic in mice (2.3 X pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl alpha- to nitrogen and the lowering action of equatorial alpha-methyl substituents in reversed esters of pethidine.