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991.
Van den Eynde I Laus G Schiller PW Kosson P Chung NN Lipkowski AW Tourwé D 《Journal of medicinal chemistry》2005,48(10):3644-3648
On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent mu-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the mu-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2',6'-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine. 相似文献
992.
The antibacterial activity of morin, sodium salt of morin-5"-sulfonic acid (NaMSA) and new complexes of La (II), Gd (III) and Lu (III) with morin were tested against three bacterial strains: Escherichia coli G (-), Klebsiella pneumoniae G (-), Staphylococcus aureus G (+) and compared with the activity of penicillin. All of the complexes possess inhibitory action against the tested strains. The activity of the studies compounds depends on their concentration. The complexes at a concentration of 10 microg/cylinder demonstrated higher activity than morin alone, but at a concentration of 100 microg/cylinder morin was the most effective inhibitor against the strains used in this investigation. 相似文献
993.
Characterization of antinociceptive activity of novel endomorphin-2 and morphiceptin analogs modified in the third position 总被引:4,自引:0,他引:4
In the present study we investigated and compared the in vivo analgesia of centrally administered endomorphin-2 and morphiceptin, and their analogs modified in position 3. Two series of analogs were synthesized by introducing unnatural aromatic amino acids in the D configuration: 3-(1-naphthyl)-D-alanine (D-1-Nal), 3-(2-naphthyl)-D-alanine (D-2-Nal), 3-(4-chlorophenyl)-D-alanine (D-ClPhe), 3-(3,4-dichlorophenyl)-D-alanine (D-Cl2Phe). Antinociceptive activity of endomorphin-2, morphiceptin, and their analogs was compared in the mouse hot-plate test, performed after i.c.v. administration of the peptides at a dose of 10 microg/animal. The best results were obtained for two morphiceptin analogs, [D-Phe3]morphiceptin and [D-1-Nal3]morphiceptin, which showed greatly improved analgesic activity, as compared to morphiceptin. In the endomorphin-2 series none of the modifications produced analogs more potent than the parent compound, but [D-1-Nal3]endomorphin-2 was the best analog. Antinociception induced by endomorphin-2 was reversed by concomitant i.c.v. administration of [D-Phe3]endomorphin-2, [D-2-Nal3]endomorphin-2, and [D-2-Nal3]morphiceptin, indicating that these analogs were weak mu-opioid antagonists. 相似文献
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Five patients with amiodarone-induced QT prolongation and torsade de pointes are described. Hypokalemia was present in three patients, marked bradycardia - in two, and T-wave alternans - also in two patients. Patients with negative T waves in precordial leads were at higher risk of ventricular fibrillation than the patients with positive T waves. Beta-blocker, lidocaine and, in two patients, tosylate bretylate were effective. All patients survived to hospital discharge, however, one patient died four months later. 相似文献
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Homma S Thompson JL Pullicino PM Levin B Freudenberger RS Teerlink JR Ammon SE Graham S Sacco RL Mann DL Mohr JP Massie BM Labovitz AJ Anker SD Lok DJ Ponikowski P Estol CJ Lip GY Di Tullio MR Sanford AR Mejia V Gabriel AP del Valle ML Buchsbaum R;WARCEF Investigators 《The New England journal of medicine》2012,366(20):1859-1869