Antiarrhythmic activity of 3-amino-3-methyloxindoles.

A series of 3-amino-3-methyloxindoles was synthesized from indoles by modification of previously described procedures. All compounds showed activity against chloroform-induced arrhythmias in mice. One member of the series, 3-methyl-3-piperidinooxindole, displayed activity equal to that of lidocaine while showing only one-third the acute toxicity.     

3-amino-3-demethoxyfortimicin A and the C-2 epimeric-2-amino-3-O-demethyl-2-deoxyfortimicins A

Selective reactions of 3-O-demethyl-3-O-methanesulfonyl-4-N, 5-O-methylenefortimicin derivatives have been used as the key steps in the syntheses of 3-amino-3-demethoxyfortimicin A and the C-2 epimeric 2-amino-3-O-demethyl-2-deoxyfortimicins A. In vitro antibacterial activities of the new fortimicin derivatives are reported.     

7-氨基-3-乙烯基头孢烷酸的合成

目的研究7-氨基-3-乙烯基头孢烷酸的合成方法。方法以7-苯乙酰氨基-3-氯甲基头孢烷酸对甲氧苄酯为起始原料，采用化学法和酶解法制得目标化合物，总收率分别达到55．6％和58．5％。结果与结论该工艺原料易得，反应条件温和，收率有所提高，具有工业生产价值。     

Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one

Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.5 microM) through reduced inducible NO synthase protein expression. PGE(2) production by LPS/IFN-gamma-stimulated macrophages was inhibited by APO at much lower concentrations (IC(50)=0.27 microM) than those required for the inhibition of NO production. Mechanistic analysis showed that APO inhibited both cyclooxygenase (COX)-1 and COX-2 enzyme activities with almost equal selectivity. Secretion of NO and the pro-inflammatory cytokine IL-6 by IFN-gamma-activated RAW264.7 cells, a murine macrophage-like cell line, was also dose-dependently reduced by APO. Furthermore, APO increased the secretion of the anti-inflammatory cytokine IL-4 by antigen-stimulated T cells and promoted the polarization of CD4(+) Th cells toward the anti-inflammatory Th2 phenotype at equimolar concentrations that inhibited NO production. Our results suggested that APO induced polarization toward the Th2 subset, at least in part through the down-regulation of IL-12 production. Thus, APO appears to have potent anti-inflammatory and immunoregulatory properties that may provide a promising therapeutic strategy for the treatment of T cell-mediated inflammatory autoimmune diseases as well as for bacteria-induced chronic-inflammatory diseases.     

Stimulatory effect of polyprenoic acid E5166 on 2-deoxy-D-glucose uptake by Swiss 3T3 cells

3,7,11,15-Tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E5166), a synthetic analog of retinoic acid, increased 2-deoxy-D-glucose (2DG) uptake in a dose and time-dependent manner in mouse fibroblasts, Swiss 3T3 cells. Kinetic analysis of 2DG uptake showed that the Vmax for 2DG uptake by E5166-treated cells was greater than that of the control, while the Km values were essentially the same. Most of the E5166-stimulated 2DG uptake was suppressed by cycloheximide, although part of the stimulation always remained despite of the cycloheximide treatment. These results suggest that E5166-induced stimulation of 2DG uptake is due to the increase in the synthesis and recycle of hexose transporters (carriers) in Swiss 3T3 cells.     

Suicide inactivation of lactoperoxidase by 3-amino-1,2,4-triazole

Amitrole (3-amino-1,2,4-triazole) meets the criteria for a suicide (mechanism-based) inhibitor of lactoperoxidase. Amitrole causes rapid inactivation of lactoperoxidase only in the presence of hydrogen peroxide, and the kinetics are consistent with a suicide mechanism. Approximately 7 mol of radiolabeled amitrole binds covalently per equivalent of lactoperoxidase activity lost. The visible spectrum of lactoperoxidase inactivated by amitrole is unchanged, suggesting that covalent modification of the heme prosthetic group does not occur. The 13C NMR spectrum of lactoperoxidase inactivated by [13C]amitrole shows unique resonances which support the hypothesis that covalent binding occurs on the protein moiety. The similarities between lactoperoxidase and thyroid peroxidase suggest a similar mechanism for inhibition of thyroid hormone synthesis by amitrole.     

Molecular structure of some 3-amino-2-oxazolidinone derivatives

It is generally accepted that the specific, energetically preferred conformation of a compound decides on the nature of interactions with pharmacological receptor. Therefore it is of basic importance to get an insight into such molecular parameters as charge distribution, most preferred conformations or the distances between specified points within a molecule. The structure of some 3-amino-2-oxazolidinone derivatives with the aid of NMR spectroscopy (13C and 15N) and X-ray analysis was investigated. Analysis of AS-8 structure revealed that the crystals of hydrochloride salt are built up of cation-anion pairs and crystallized with molecule of water. The results allowed to identify the primary place of the molecule interaction with an acid residue within putative receptor site.     

帕米膦酸二钠的合成

目的：合成二钠３－氨基－１－羟基－亚丙基－二膦酸盐（帕米膦酸二钠）。方法：有,无溶剂的两种合成路线,并对工艺进行改进,所得产物经元素分析,红外光谱,质谱等分析确证结构。结果;两种路线均可合成目标化合物。路线Ａ收率高于路线Ｂ。结论：溶剂的加入使本反应体系均一,有利于产物生成。