Cytostatic

In addition to the sex hormones and corticosteroids, other steroid dmgs have substantial worldwide markets. For example, cytostatic hormones had worldwide sales of approximately 1.8 biUion in 1994. Included in these 1.8 biUion are several steroids or steroid-mimetics such as megestrol acetate and tamoxifen (282), respectively (262). 

Pyrolyses of Nl- or N3-substituted derivatives of compounds 4 and 5 have continued to find use as routes to azacarbazoles, although the yields are often indifferent and there are no recent examples. The photochemical reactions are dealt with in Section IV.G. Pyrolysis media are paraffin (P) or PPA, and examples of products are compounds 247 (P, cytostatic) (83MI2), 248 (P) (84MI1), and 249 (from a 1-substituted derivative) (86MI2). Indications of diradical intermediates are provided by the thermolysis of compound 250 (P) (83MI2) where one product is a dimer. 

The unsaturated substituent in the carbene complex 1 often is aromatic or heteroaromatic, but can also be olefinic. The reaction conditions of the Dotz procedure are mild various functional groups are tolerated. Yields are often high. The use of chromium hexacarbonyl is disadvantageous, since this compound is considered to be carcinogenic however to date it cannot be replaced by a less toxic compound. Of particular interest is the benzo-anellation procedure for the synthesis of anthra-cyclinones, which are potentially cytostatic agents. ... 

German investigators (Brock et al) worked on the creation of alkylating pro-drugs that have cytostatic activity after specific biotransformation in the tumor tissue. Cyclophosphamide (CTX) has well pronounced antitumor activity with the broadest spectrum. It is metabolized to the cytotoxic phosphoamide mustard. In normal tissues with high enzyme level cyclophosphamide is converted to its inactive metabolites (Fig. 2). These differences in biotransformation can explain the relative selectivity of cyclophosphamide towards... 

Dacarbazine is the most active compound used for treating metastatic melanoma. It is also combined with anthracyclines and other cytostatics in the treatment of different sarcomas and Hodgkin s disease. Dacarbazine may cause severe nausea and vomiting. Myelosuppres-sion results in leukopenia and thrombocytopenia. Alopecia and transient abnormalities in renal and hepatic function also occur. 

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. 

Anticancer diugs Cytostatic drugs Cytotoxic drags Antitumor drags... 

Side effects are less prominent in type and extent as compared with cytostatics and include typical hormonal or lack of hormone like effects. 

Treatment for tumor patients with synthetic drags -chemotherapeutics - that may be of completely different chemical structure. The main goal of tumor chemotherapy is to achieve a selective toxicity for the tumor without causing damage to the host, for instance by combining several cytostatic drags at doses lower than required for monotherapy. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

In view of the importance of the motor dynein for microtubular function, this protein is currently considered as a new target for the development of cytostatic agents. 

A prodrag is a drug that is not by itself pharmacologically active but needs metabolic activation by an enzyme. Examples are the cytostatic cyclophosphamide, which is activated by hydroxylation catalyzed by CYP2B6, or HMGCoA reductase inhibitor, lovastatin, which contains... 

II cleaves the two complementary strands of DNA four base pairs apart and the resulting 5 -phosphoryl groups become covalently linked to a pair of tyrosine groups, one in each half of the dimeric topoisomerase II enzyme. Several groups of drugs are known that selectively inhibit topoisomerases in bacteria (quino-lones) or mammalian cells (etoposide, tenoposide). Quinolones are used to treat bacterial infections inhibitors of mammalian topoisomerases are cytostatic drugs used for the treatment of cancer. 

Cytomegalovirus CMV Cytoplasmic Tyrosine Kinases Cytoskeleton Cytostatic Drugs... 

An example of a separation primarily based on polar interactions using silica gel as the stationary phase is shown in figure 10. The macro-cyclic tricothecane derivatives are secondary metabolites of the soil fungi Myrothecium Verrucaia. They exhibit antibiotic, antifungal and cytostatic activity and, consequently, their analysis is of interest to the pharmaceutical industry. The column used was 25 cm long, 4.6 mm in diameter and packed with silica gel particles 5 p in diameter which should give approximately 25,000 theoretical plates if operated at the optimum velocity. The flow rate was 1.5 ml/min, and as the retention time of the last peak was about 40 minutes, the retention volume of the last peak would be about 60 ml. 

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