Corticosteroids structural groups

Other groups also made attempts to separate local and systemic effects by integrating moieties susceptible to rapid, nonhepatic metabolism within the corticosteroid structure. One of the more successful attempts explored 17a-(alkoxycarbonyl)alkanoate analogs (35) of clobetasol propionate (144). Again, this can be considered as a hypothetical inactive metabolite—based approach, and a corresponding metabolite (35)(n. = 2, R = H) has indeed been shown to be inactive. Esters that were susceptible to rapid hydrolysis exhibited good separation of topical anti-inflammatory to systemic activity. The study also indicated the existence of an optimal volume for the 17a side chain. For example, the methyl succinate derivative (35) (/i = 2, R = methyl) showed as potent topical anti-inflammatory activity as clobetasol propionate, but a dramatically reduced thymolytic activity. Therefore, the cor-... 

Fig. 12.1 Corticosteroids from the four structural groups taneperhydrophenanthrene nucleus of 17 carbons shown A, B, C, and D classified on the basis of clinical cross- numbered on the hydrocortisone structure in a. Note that...

Aldosterone, essentially a corticosteroid in which the methyl group at Cjg is oxidized to a carboxaldehyde, was the last endogenous steroid to be isolated in a form suitable for structural studies. This hormone controls via its action on the kidney both body electrolyte balance and blood volume. A number of modified androstanes, all of which feamre a spirobutyrolactone at C17, act as aldosterone antagonists Those 17-spirobutyrolactones consequently show diuretic and... 

In connection with the work on the relationship between chemical structure and anti-inflammatory activity, the effect of ursolic acid, betulin, betulinic acid and erythrodiol on a system of chronic dermal edema and cellular proliferation caused by repeated administration of TPA has recently been examined [89], This experimental model of chronic inflammation has considerable selectivity for corticosteroids and leukotriene synthesis inhibitors. Erythrodiol and ursolic acid were significantly effective and also reduced the neutrophil infiltration detected by MPO activity. The lupane derivatives, betulin and betulinic acid, despite their possible steroid-like mechanism of action [47], were not effective in the chronic model. This result could mean that a six-member E ring of the pentacyclic structure is necessary for the activity against a multiple dose of TPA. The data confirm that a hydroxyl group at the C-28 position is important for the activity, as is also true in the case of erythrodiol, and it may explain the anti-inflammatory effect of this compound in each of the methods. 

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