Disposition of glipizide in patients with liver cirrhosis

The effect of moderate alcoholic liver cirrhosis, in nondiabetic patients, on the kinetics of a single oral dose [5 mg] of the hypoglycemic sulfonylurea agent, glipizide [GPZ], was investigated. The results were compared with those reported for healthy subjects and diabetic patients. The study revealed that there was no significant alteration in the pharmacokinetics profile of GPZ under moderate liver cirrhosis. However, in one patient, who had moderate cirrhosis accompanied by fibrosis, there was a marked increase in half-life [2.4 v 8.6 h] and AUC [3710 v 13171 nmol L -1 h] and large reduction in clearance [2.96 v 0.83 L h -1] when compared with a matching healthy subject. The results suggested that liver fibrosis may contribute to alteration in the kinetics of GPZ

Inhibition of herpesvirus ribonucleotide reductase by new synthetic peptides

The prospect of total chemical synthesis of large biologically active peptides up to the protein size has always represented a powerful tool in bioorganic chemistry. The advances made in the chemical synthesis of peptides would not have been possible without the availability of solid phase peptide synthesis [SPPS] introduced by Merrifield[1]. Since the conception of [SPPS], the chemistry developed for its application has remained fairly standardized. Like all ingenious ideas, [SPPS] also has its short-comings, for example the repetitive acidolysis required for the deprotection of [Boc] group, which may affect the acid sensitive peptide bonds and also catalyze some undesirable side reactions result in failure sequences. This initiated the development of different N-alpha-aminoblocking groups. However, the most successful one was the base labile 9-fluorenyl methoxycarbonyl Fmoc group, which is considered one of the best choices for protecting the alpha-amino-group not only because of its cleavage in weak alkaline medium [e.g. piperidine in DMF] and can therefore be used in conjunction with acid labile linker, acid sensitive amino acids and side chain protecting groups, but also because it enables- as UV active group- continuous spectroscopic monitoring during all steps of synthesis cycle[2]

facile conversion of aldehydes into nitriles via the sulphonyl hydrazones

Although many reagents are available to affect the conversion of aldehydes to nitriles, the majority is electrophilic in character, or require acidic conditions. Recently, thermal d composition [Scheme 1] of aldehyde derivatives in a concerted way offers an alternative for this conversion, in cases where thermal liability or inviolability does not offer an additional obstacle. In the second reaction [B], reactions due to radical fragmentation were the main reasons for the decreased yield of nitriles, since these produce in addition ozines and consequently ethylene. In order to drive the reaction completely towards the concerted pathway, we investigated the thermal fragmentation of N[1] benzoylphenylhydrazones, where steric factors may give the correct orientation for the transition state required for the concerted pathway and that leading to the exclusive formation of nitriles and benzanilide [Scheme2] In this case, we found that the pyrrolysis of the hydrazones Ia-f yields as anticipated mainly the desired nitrile III and benzanilide, however the pyrrolysis occurred only above 260 degree [230 - 320degree] and the yields of the nitriles range from 50-70 percent