Semisynthetic drugs tetracyclines

Structural modification of the tetracyclines obtained by fermentation has resulted in very few additional clinically useful semisynthetic drugs. However, those developed (DC, MC, MNC) have some advantageous features over the original compounds. Also, from data of both in vitro and in vivo studies on many bacteria using a large number of tetracyclines obtained by fermentation and synthetic alterations, it became apparent what the structural requirements for good activity are. Table 6-10 summarizes the salient features that... 

In addition to the above examples, there are still a large number of bioactive natural products and various synthetic and semisynthetic enol-containing compounds that serve as potential and promising drugs for various therapeutic purposes such as the non-peptidyl HIV inhibitor Aptivus (tipranavir Section IV.1) and the third-generation tetracycline antibiotics (Section IV.H). The structure and function of the metal complexes of some... 

Doxycycline is a semisynthetic, tetracycline, antibiotic drug. Doxycycline hyclate (doxycycline hydrochloride hemiethanolate hemihydrate) injection solutions (100mg/5mL) may be administered by slow IV injection or by IV infusion (maximum four hours). Reconstituted solutions, in either 0.9% sodium chloride injection or 5% dextrose injection, are stable for 48 hours under fluorescent lamps (Product Information Sheet, Vibramycin , 1995). 

Here as with the tetracyclines, the solution of difficult chemical problems was a prerequisite to successful new drug discovery. At first the counterpart of 6-aminopenicillanic acid could be made only in very low yields by chemical hydrolysis. A practical enzymatic hydrolysis of cephalosporin C to 7-aminocephalosporanic acid (7-ACA) was not found. R. B. Morin and co-workers provided the elegant solution (Figure 21) (101), which made the preparation of 7-ACA and semisynthetic cephalosporins possible on a practical scale. The impetus to persevere in this... 

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