ABSTRACT
Bioisosterism is one of the most common strategies in drug structure optimization. With the development of medicinal and organic chemistry, more and more classic and non-classical bioisosteres are used in the design of novel drugs. In recent years, fluorinated groups as a bioisostere have been paid more and more attention by pharmaceutical chemists. This paper briefly reviews the physicochemical properties, chemical preparation methods of difluoromethyl (CF2H) group, and its application in drug design to provide references for drug discovery researchers.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of HSGJ on chronic allograft nephropathy (CAN) using standard rat model of CAN.</p><p><b>METHOD</b>Renal transplantation was performed with Fisher rats as donors and Lewis rats as recipients. All the recipients were randomly divided into control group and medication groups (high and low dosage of HSGJ, fed every other day). After 16 weeks of treatment, renal function and the histological alteration of CAN were measured. The expression of the TGFbeta1 mRNA in the allograft was evaluated by real-time PCR.</p><p><b>RESULT</b>The content of 24 h urine protein and the level of serum creatinine in the medication groups were significantly decreased (P < 0.01) as compared with control group, whereas the creatinine clearance was increased (P < 0.01). The degree of glomerular sclerosis and the Banff score of medication groups were lower than the control group respectively (P < 0.01), in consistent with decreased expression of the TGF 1mRNA.</p><p><b>CONCLUSION</b>HSGJ can prevent the chronic allograft nephropathy and the mechanism may be related with its influence on the expression of the TGFbeta1.</p>