Parent tetracyclines

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

The hemiketal products (11) and (12) have been converted to the corresponding oximes, hydra2ones, and substituted amines (40,41). Although many of these derivatives exhibit substantial antibacterial activity, they are generally less active than the parent tetracyclines. 

The 6- uoro isomers, 6-deoxy-6-demethyl-6a- uorotetracycline [24333-20-8] C2 H2 FN20y, and 6-deoxy-6-demethyl-6P- uorotetracycline [24333-21-9] C2 H2 FN202, have been prepared and showed relatively high in vitro and in vivo biological activities compared to the parent tetracyclines. 

Deoxy-7-demethyl-6a-fluorotetracycline and the corresponding 6p- isomer have been synthesised and exhibit high activities compared to the parent tetracyclines. Acquired resistance to tetracyclines has been an impediment to their clinical use and in this context semi-synthetic studies which have already been very extensive have resulted in the introduction of valuable compounds such as minocycline. 

It is, however, interesting to observe that the subsequent removal of the 4-dimethylamino function affords a loss of about 75% of the antibiotic effect of the parent tetracyclines. 

It must be established that the analyte remains stable throughout the analysis. There have been some reports in the literature of conversion of the analytes to apparent metabolites or degradation products, such as in the case of tetracyclines, and this can certainly confuse the interpretation of the analytical results. This has led some jurisdictions to amend MRLs to take account of this phenomenon. For example, in the EU, the MRL for the various tetracyclines is expressed as the sum of the parent tetracycline and the 4-epimer of the veterinary drug. ... 

M.p. 296 C. Accepts an electron from suitable donors forming a radical anion. Used for colorimetric determination of free radical precursors, replacement of Mn02 in aluminium solid electrolytic capacitors, construction of heat-sensitive resistors and ion-specific electrodes and for inducing radical polymerizations. The charge transfer complexes it forms with certain donors behave electrically like metals with anisotropic conductivity. Like tetracyanoethylene it belongs to a class of compounds called rr-acids. tetracyclines An important group of antibiotics isolated from Streptomyces spp., having structures based on a naphthacene skeleton. Tetracycline, the parent compound, has the structure ... 

Tetracycline Sum of parent drug and All food-producing Muscle 100 ... 

Asker AF, Habib MJ. Effect of certain additives on photodegradation of tetracycline hydrochloride solutions. J Parenter Sci Technol 1991 45 113-115. 

Fate All the tetracyclines concentrate in the liver, where they are, in part, metabolized and conjugated to form soluble glucuronides. The parent drug and/or its metabolites are secreted into the bile most tetracyclines are reabsorbed in the intestine and enter the urine by glomerular filtration. Doxycycline is an exception, since its metabolite is preferentially excreted via the bile into the feces. Thus, unlike other tetracyclines, doxycycline can be employed in treating infections in renally compromised patients. 

In practice, treatment of amoebiasis can be divided into treatment of bowel lumen amoebiasis, and tissue-invading amoebiasis. The bowel lumen infection, which is usually asymptomatic, may be in trophozoites form (non-infective) or in cysts form (infective) and treatment is directed at eradicating cysts with a luminal amoebicide (e.g. diloxanide). The tissue-invading amoebiasis (giving rise to dysentery, hepatic amoebiasis and liver abscess) must be treated with systemically active drugs (systemic amoebicides) active against trophozoites (e.g. metronidazole, tinidazole also, in dangerously ill patients dehydroemetine may be used, which is less toxic than the parent emetine (derived from ipecacuanha). Sometimes antibiotics (e.g. tetracycline) are used concurrently to stop opportunist infections. 

One year later, the American pharmaceutical company Pfizer discovered a related structure - christened oxytetracycline (Terramycin) - from Streptomyces rimosus. Interestingly, this was found in a soil sample located near their factory in Terre Haute, Indiana. The parent structure - tetracycline - was then obtained by chemical removal of the chlorine atom (an element only rarely found in terrestrial organisms but common in natural products from marine organisms) from chlortetracycline. This third antibacterial agent was subequently found naturally as a constituent of both Streptomyces aureofaciens and Streptomyces viridifaciens. The structures of chlortetracycline were established by R.B. Woodward in 1952 and that of oxytetracycline by Pfizer scientists (in collaboration with RBW) in 1952. 

---