ABSTRACT
In a series of bradykinin B1 antagonists, we discovered that replacement of oxopiperazine acetamides with dehydro-oxopiperazine acetamides provided compounds with enhanced activity against the B1 receptor. The synthesis and SAR leading to potent analogs with reduced molecular weight will be discussed.
Subject(s)
Acetamides/pharmacology , Bradykinin B1 Receptor Antagonists , Piperazines/pharmacology , Acetamides/chemical synthesis , Acetamides/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The effects of the variables, including the concentrations of glucose, sucrose, corn steep liquor (CSL) and peptone, and the conditions of fed-batch culture, on CoQ10 fermentation by Rhizobium radiobacter WSH2601 were assessed. The results showed that the optimum concentrations of glucose, sucrose, CSL and peptone were 30 g/L, 40 g/L, 11 g/L and 16 g/L respectively. Addition of CSL and tomato juice stimulated the cell growth. CSL, L-methionine and isopentyl alcohol efficiently increased the biosynthesis of CoQ10. In a 7L fermentor, the fed-batch culture improved both cell growth and CoQ10 production compared to a batch culture; and suitable mixed feeding of CSL and sucrose enhanced CoQ10 yield to 52.4 mg/L. The DCW reached 26.4 g/L, an increase of 53% in comparison to that without feeding, and an increase of 24% to that feeding with sucrose only. The C/B value reached 2.38 mg/g(DCW), representing an increase of 33% to that of without feeding, and an increase of 26% to that of feeding with sucrose only.
