Corticosteroid analogues

Introduction 419 Corticosteroid Analogues 420 Cortisone 422 Hydrocortisone 423 Prednisone and Prednisolone 424 Fludrocortisone 424... 

Phillipps GH, Bailey EJ, Bain BM, et al. Synthesis and structure-activity relationships in a series of antiinflammatory corticosteroid analogues, halomethyl androstane-17(3-carbothioates and -17(3-carboselenoates. J Med Chem 1994 37 3717-3729. 

Efforts toward producing synthetic steroids, particularly cortisol, expanded during World War II to enable researchers to explore the possibiUty of medicinal appHcations of corticosteroids. In 1948, the discovery that cortisone dramatically alleviates the symptoms of arthritis led to intensive research on the antiinflammatory properties of corticosteroids. The development of partial and total syntheses for the commercial preparation of cortisone, alternative methods for producing cortisone, and the search for more potent antiinflammatory analogues gready stimulated both academic and industrial steroid research. 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

Tetracosactide (tetracosactrin) is an analogue of corticotrophin (ACTH) and is used to test adrenocortical function. It is administered by intramuscular injection. Side-effects are very similar to those with corticosteroids. 

A synthesis of the B-ring aromatic corticosteroid (286), the analogue of cortex-olone, started with the previously reported B-ring aromatic norpregnane (285). Development of the corticosteroid side-chain employed bromination of the 17a-hydroxy-20-oxo-derivative with trimethylphenylammonium bromide perbromide. " Reaction of perchloryl fluoride with the mixed enol ethers (287) and (288) provided, after hydrolysis, the 17a-fluoro-20-oxo-compound (290) and the 21-fluoro-20-oxo-compound (291). In contrast, the enamine (289) led only to the 17a,21-difluoro-20-oxo-compound. A series of 17a-acyloxy-21-deoxy-... 

Thus, in patients with Addison s disease or other forms of adrenal insufficiency, continuing oral administration of cortisone acetate or fludrocortisone acetate enables salt balance to be restored. Other corticosteriods and analogues that have been used in the hormonal control of sodium levels include aldosterone and deoxycortone acetate. Individual corticosteroids vary in the extent to which they possess the various hormonal activities so that combination therapy is usually required if, for example, mineral balances are to be maintained when corticosteroids are administered for their anti-inflammatory, antirheumatic or anti-allergic properties. 

The management of cancer includes treatment with alkylating agents (nitrogen mustards and alkyl sulfonates), antimetabolites (methotrexate and purine analogues), natural products (vinca alkaloids and taxol), miscellaneous compounds (hydroxyurea, procarbazine, and m-platinum), hormones (estrogens and corticosteroids), and radioactive isotopes. 

Ethynyl groups attached to various skeletons were generally oxidized to the hydroxyacetyl functionality. The reaction was useful in the synthesis of natural products and analogues with a dihydroxyacetone side chain, e.g. adriamycin and corticosteroids. Some examples are given in Table 4.1. 

Of other applications to biological samples we can cite the determination of urine metabolites of androst-5-en-17-ones [324], Some saturated substrates did not separate from their unsaturated analogues on OV-17 and therefore preliminary epoxidation with m-chloroperbenzoic acid was used in order to resolve them. Simpson [325] analysed corticosteroids in rat muscles and also reported mass spectra of their derivatives. Berthou... 

Corticosteroids From Natural Products to Useful Analogues... 

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