Corticosteroids compounds

Table 1. Topical Corticosteroid Compounds—Drug Facts and Comparisons vs AFIFSDrug Information...

Periodic acid is a selective reagent for the cleavage of 1,2-dioIs and related substances, such as l-amino-2-hydroxy compounds, 1,2-diketones and a-hydroxyketones. With periodic acid, corticosteroid compounds (where R= H, OH), can be transformed into 17(Lcarboxylic acids and formaldehyde. 

The predominant clinical use of corticosteroids is a result of their associated antiinflammatory properties. These are commonly used as topicals for the suppression of symptoms, including inflammation, occurring in a particular disease state these compounds are rarely considered curative in their usage. Many other disease states do, however, respond well symptomatically to treatment with corticosteroid therapy. Some of these (11) are Hsted below. 

In 1973 D-homo corticosteroids (109—112), eg, D-homo-9a- uoroprednisolone acetate (111) were reported to have antiinflammatory activity (107). Compounds such as 21-acetoxy-liP- uoto-9a-chloto-17aa-hydtoxy-D-homo-ptegn-4-en-3,20-dione (110) had especially strong topical activity with weak systemic activity (108). Other preparations of D-homocorticoids included... 

The uses of corticosteroid antiinflammatory dmgs in veterinary medicine are many and varied. In the intact animal, the glucocorticoids and mineralcorticoids are produced in the adrenal glands. Exogenous compounds are, therefore, used for their glucogenic physiologic effect in cases where the... 

These compounds vary in their specific mechanism of action and often have different effects on the individual patients. Thus, they are generally used in combinations, eg, corticosteroids with an alkylating agent, or an antimetaboUte with a plant alkaloid in a rotating schedule. 

The 21-hydroxyl group in the corticosteroid series can be protected as the base stable triphenylmethyl ether and tetrahydropyranyl ether. " " Mixed acetals from 21-alcohols are extremely acid sensitive compounds. ... 

A preponderance of the work devoted to steroids, as judged from the number of compounds bearing generic names, has clearly been that in the area of corticosteroids related... 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

Many of these compounds have been shown to be effective in the treatment of arthritis. Since they apparently work by a mechanism different from that of the corticosteroids and are structurally unrelated, they have no corresponding endocrine effects. 

The biological activity of a compound can often be affected dramatically by the presence of even a single fluorine substituent that is placed in a particular position within the molecule. There are diverse reasons for this, which have been discussed briefly in the preface and introduction of this book. A few illustrative examples of bioactive compounds containing a single fluorine substituent are given in Fig. 3.1. These include what is probably the first example of enhanced bioactivity due to fluorine substitution, that of the corticosteroid 3-1 below wherein Fried discovered, in 1954, that the enhanced acidity of the fluorohydrin enhanced the activity of the compound.1 Also pictured are the antibacterial (3-fluoro amino acid, FA (3-2), which acts as a suicide substrate enzyme inactivator, and the well-known anti-anthrax drug, CIPRO (3-3). 

Corticosteroids (i.e., steroidal compounds) found in urine that possess biological properties resembling those of adrenal cortical extract, either in the increase or decrease of cholesterols levels,... 

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