Androgenic and anabolic agents

Androgens and anabolic agents have been used in the treatment of osteoporosis, either alone or in conjunction with estrogens. With the exception of substitution therapy in hypogonadism, bisphosphonates have largely replaced androgen use for this purpose. 

Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention. 

The aim of this work is to review the structure-activity theories in the field of androgens and anabolic agents. It is written primarily for medicinal chemists and pharmacologists, but other research scientists, such as endocrinologists and biochemists, may also find it of value. 

In Chapter 4 the therapeutic action of androgens and anabolic agents is examined. In Chapter 5 some 650 androgens and anabolic agents are compiled. The literature is covered through 1967. Some compounds could not be incorporated into the tables owing to the lack of biologic data. 

Excellent accounts of the biological effects and clinical application of anabolic steroids, by Kriiskemper [5], and of the pharmacology of anabolic steroids, by Overbeek [50], are available. It is the aim of this book to examine the chemical structure-biological activity relationship of androgens and anabolic agents. A new theory of steroid-receptor interaction is also advanced, based on a new approach to the chemical structure-biological activity relationship. 

The natural androgen testosterone and a large number of other androgens and anabolic agents possess the 4,5-double bond, while the majority of metabolic products lack this unsaturation. The hypothesis was put forward that the reduction of the 4,5-double bond in the liver may represent the rate-limiting step in the inactivation of these hormones [168,221]. Upon hydrogenation of the double bond, the 5-carbon becomes asymmetric and therefore two possible isomers could result, the 5a-isomer (trans... 

Reduction of the 3-ketone group can give rise to 3a- or 3/3-hydroxy compounds, with the former dominating in men. Of the two epimers, the 3a-hydroxy compounds are usually the more potent androgens and anabolic agents. A contrary example was given by Dorfman [241] ... 

Since we feel that perhaps better results can be obtained from another viewpoint, we propose to consider the mechanism of action by an approach considering the minimal structural requirements necessary to bring about hormonal activity. We must remember that the natural androgen and anabolic agent, testosterone, does not display the minimum structural requirements of active steroids —there are many steroids which are less active testosterone itself is an excellent androgen and a good anabolic agent. 

Calmurid hydrocortisone, calusterone [inn, usan] (NSC 88536 U 22550) is a steroid, an ANDROGEN and ANABOLIC AGENT, used as an ANTICANCER AGENT. It has experimental haematopoietic effects, camazepam [inn] (SB 5833) is one of the [l,4]benzodiazepines, a benzoduzepine BINDING-SITE AGONIST, with similar properties to diazepam. It has... 

Stallimycin [inn] (stallimycin hydrochloride [usan] distamycin A) is a (peptide) ANTIBIOTIC active as an ANTIVIRAL. It is used topically to treat herpes simplex infections. Stallimycin hydrochloride stallimycin. Stanolone [ban] (androstanolone [inn] androstanolone propionate androstanolone enanthate dihydrotestosterone) is a steroid, an androgen and ANABOLIC agent. It has been used orally and topically in the form of an eye ointment. 

Table 4 Melting point [17] of androgens and anabolic agents.

Vida JA. Androgens and Anabolic Agents Chemistry and Pharmacology. New York Academic Press, 1969. 

ANDROGENIC AND ANABOLIC AGENTS FORMULA MOL. 1 WT. SOLVENT Icm m/u SOLVENT ... 

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