Related Antiinflammatory Steroids

It was known as early as 1927 that the adrenal glands of mammalian species secrete a series of substances essential to the survival of the individual. The hormonal nature of these secretions was suggested by the observation that extracts of the adrenal gland and more specifically of the outer portion of that organ (cortex) would ensure survival of animals whose adrenals had been excised. By 1943 no fewer than 28 steroids had been isolated from adrenal cortical extracts. These compounds were found to be involved in the regulation of such diverse and basic processes as electrolyte balance, carbohydrate metabolism, and resistance to trauma, to name only a few. 

as in the case of the other steroid hormones, the quantities of these compounds isolable from animal sources was 

As is apparent at a glance, cortisone is an intricate molecule with a wealth of functionality. Steroid transformations in the corticoid series require serious strategic planning in order to provide the appropriate protecting groups and to introduce substituents in the proper order. It is therefore easy in a discussion of this chemistry to get lost in a welter of detail. 

For this reason in this section we depart from our practice of discussing each synthesis in detail. Certain standard operations, for example, introduction of 9-fluoro substituents, are referred to as though they were a single reaction only the salient points of the syntheses are dwelt on. Examination of some of these syntheses strongly suggests that these were aimed at preparing compounds for biologic assay. It is more than likely that the commercial preparations have only the final product in common with the published route. 

One of the first indications that the antiinflammatory potency of the corticoids could be increased was the observation that incorporation of a 9a-fluoro group in hydrocortisone resulted in a tenfold increase in activity. Treatment of hydrocortisone acetate (170a) with phosphorus oxychloride in pyridine yields the corresponding olefin, 172. This, on being subjected to the reaction sequence depicted in the transformation of 104 to 108 (addition of HOBr, closure to the epoxide and ring opening with HF), 

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Vitamin D is a precursor for a number of compounds that increase intestinal absorption and decrease renal excretion of calcium and phosphate. Metabolites of vitamin D and their pharmacologic analogs are typically used to increase blood calcium and phosphate levels and to enhance bone mineralization in conditions such as osteodystrophy, rickets, or other situations where people lack adequate amounts of vitamin D. Vitamin D analogs such as calcitriol have also been combined with calcium supplements to help treat postmenopausal osteoporosis,4,9 and to treat bone loss caused by antiinflammatory steroids (glucocorticoids see Chapter 29 28.76 Specific vitamin D-related compounds and their clinical applications are listed in Table 31-5. 

Amino-l,3-dioxepines were synthesised as potential new non-steroidal antiinflammatory agents by the reaction of an aldehyde with the appropriate amino-diols <07BMC6273> while benzodioxepines related to the marine odorant Calon 1951 have been synthesised and the nature of substituents on olfactory character analysed <07HCA854, 07HCA1006>. 

Taha AS, Nakshabendi I, Lee FD, Sturrock RD, Russell RI. Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal antiinflammatory drugs comparison and correlation with peptic ulceration. J Qin Pathol 1992 45(2) 135-9. 

Clinical trials have revealed that diseases that are related directly to excessive TNF production, such as septic shock, GVHD, and lupus nephritis, may be amenable to treatment either with anti-TNFa antibodies or with antiinflammatory agents that reduce TNF production, such as cyclosporin A and steroids. ... 

ABSTRACT Saponins are natural glycosides of steroid or triterpene which exhibited many different biological and pharmacological actions e.g. immunomodulatory, antitumor, antiinflammatory, molluscicidal, antiviral, antifungal, hypoglycemic, hypocholesterolemic, to mention just a few. The aim of this review is to summarize recent advances on the bioactivity of saponins related to cancer and immune system, which has attracted a great attention during the last five years. 

Corticosteroids traditionally are divided into mineralocorticoids and glucocorticoids according to their relative potencies in Na retention and effects on carbohydrate metabolism i.e., hepatic deposition of glycogen and gluconeogenesis) In general, potencies of steroids to sustain life in adrenalectomized animals closely parallel their mineralocorticoid activity, while potencies as antiinflammatory agents closely parallel their effects on glucose metabolism. The effects on Na" retention and the carbohydrate/anti-inflammatory actions are not closely related and reflect selective actions at distinct receptors. 

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