Amidinobenzisothiazole derivatives with antidegenerative activity on cartilage

N-(Benzo[d]isothiazol-3-yl)amidines were synthesised and evaluated for their antiinflammatory activity. Encouraging results led us to evaluate these derivatives on the prevention of cartilage destruction in articular disease. Antidegenerative activity was assayed on culture of porcine nasal cartilage and diarthroidal joint human cartilage in the presence of interleukin-1beta (IL-1beta). The amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) in the culture medium were determined. The obtained results showed that all the compounds, in the presence of IL-beta, blocked the cartilage breakdown, with different behaviour. The antidegenerative activity is more evident in human cartilage.     

Synthesis and Biological Investigations of Pyrimidine Derivatives

The study concerns new syntheses of 5-hydroxy ether and 5-aminohydroxy ether derivatives of pyrimidine. When tested for antibacterial activity, some of the compounds exhibited promising effects.     

Investigations on the pharmacokinetics of apalcillin in man

Plasma levels and urinary excretion was studied after i.v. bolus of 1000 mg (2S,5R,6R)-6-[(R)-2-(4-hydroxy-1, 5-naphthyridine-3-carboxamido)-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (apalcillin, PC-904) and after long-term infusion of 3000 mg apalcillin in volunteers of both sexes. For measuring the concentrations a cylinder agar diffusion test was used. The plasma levels decreased from 150 microgram/ml 2 min after injection to 100 microgram/ml 15 min p.a. and to 37 microgram/ml after 90 min. For the terminal half-life of elimination from plasma a value of 1.0 was calculated. After termination of the long-term infusion concentrations of 70-80 microgram/ml were found in plasma. In this case a terminal half-life of 1.5 h was calculated. Due to the fast half-life of elimination no cumulation will occur in the case of repetitive dosing. This suggestion is supported by the finding, that the mean transit time of 1.4 h is very short. On the other hand the substance is distributed so rapidly that therapeutic levels are reached 30 min after infusion. Using data from literature, a proportionality between dose and area under the plasma curve could be demonstrated in the range 1000-3000 mg apalcillin. Our results show that about 20% of the dose administered is found in urine. 10 h after application the urinary excretion is finished. No side effects were observed during the acute assays.     

Investigations in the Thiazolidine Series

Several spirothiazolidines and N-acyl derivatives of ethyl thiazolidine-4-carboxylate have been synthetised. IR and NMR spectra have been studied. Pharmacological studies show GABA agonist activity for one of the spirothiazolidines and weak antimicrobial activity for two of them. No activity was apparent in a leukemia screen test.     

Investigations on harpagophytum.

Comparing the analytical results of the constituants of naturally growing roots and callus of HARPAGOPHYTUM PROCUMBENS, it could be demonstrated that both, the products of the primary and the secondary metabolism, showed important differences. Harpagosid which is present in significant amounts in the roots and tubers of the fresh plants, was shown to be completely absent in the callus. Stachyose the main reserve carbohydrate again was only produced in minor amounts. Fructose was the predominant sugar in the callus cells.     

水飞蓟宾衍生物的研究进展

介绍近年来通过对水飞蓟宾进行结构修饰以改进其溶解性和生物活性的研究进展。水飞蓟宾具有抗脂质过氧化、清除自由基、保护肝细胞、抗肝纤维化和免疫调节等作用,但因溶解性差、生物利用度低,其临床应用受到一定限制。故以水飞蓟宾为先导化合物合成相关衍生物,并从中筛选专一性强和活性高的化合物,已成为广受关注的研究热点。     

Synthesis and Antituberculous Activity in vitro of Amidine and Hydrazidine Analogs of Pyrazinamide and Isoniazid

Pharmaceutical Chemistry Journal -     

抗慢性心功能不全药研究进展

由于心血管系统疾病发病率的增高及人口的老龄化,慢性心功能不全的发病率也在逐年上升,其较高的致残率和病死率已成为严重的公共卫生问题.随着分子生物学的发展,人们对心衰发生发展机制有了更深入的认识,从而带动了心衰药物治疗的研究和发展.     

Investigations on the micellisation behaviour of fenoprofen sodium

The aim of the present study was to investigate the micellisation behaviour of the non-steroidal anti-inflammatory drug fenoprofen sodium in aqueous solutions. The methods used were foam stability measurements, ¹H-NMR, solubilisation, photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM). Results from surface tension measurements performed in a previous study were included. A great discrepancy between critical values from different experimental methods was found. Methods that detect changes in the surface properties of aqueous fenoprofen sodium solutions suggest that the critical concentration was 1.5110⁻² mol/l, while methods that detect changes in the bulk phase led to a critical concentration of 1.2110⁻¹ mol/l. In the concentration range between 1.5110⁻² and about 1.0110⁻¹ mol/l no formation of aggregates could be detected (concluded from the absence of an upfield shift of the phenyl proton signals in the NMR measurements and the finding that the oily, practically water insoluble fenoprofen acid could not be solubilised by fenoprofen sodium solutions below concentrations of 1.0110⁻¹ mol/l fenoprofen sodium). Association of fenoprofen sodium molecules to micelles starts at concentrations between 1.0 and 1.2110⁻¹ mol/l. In conclusion, the determination of the critical micelle concentration from surface tension measurements does not allow the determination of micellisation phenomena in the case of fenoprofen sodium. Further methods are required to assure micellisation. Photon correlation spectroscopy and TEM support the assumption that fenoprofen sodium forms disclike micelles, although with both methods the micelle size could not exactly be determined. From differences in the chemical shift of the two phenyl rings of fenoprofen sodium it was concluded that the micelles have a bilayer or partially overlapping bilayer structure.