Derivatives of testosterone

Oil-soluble derivatives of testosterone itself predate those of its 19-nor congener these agents too are used to administer depot injections so as to provide in effect long-term blood levels of drug. Thus, acylation of testosterone with propionyl chloride in the presence of pyridine yields testosterone propionate (76a)acylation by means of decanoic anhydride yields testosterone decanoate (76b).Finally, reaction of 75 with 3-cyclopentylpropionyl chloride affords testosterone cypionate (76c)This last undergoes hydrolysis unusually slowly because of the presence of two substituents at the 5 position (see Newman s Rule of 6). ... 

Steroids that aid in muscle development are called anabolic steroids. They are synthetic derivatives of testosterone, thus have the same muscle-building effect as testosterone. There are more than 100 different anabolic steroids which, vary in structure, duration of action, relative effects and toxicities. Androstenedione, stanozolol and dianabol are anabolic steroids. They are used to treat people suffering from traumas accompanied by muscle deterioration. The use of anabolic steroid can lead to a number of dangerous side-effects, including lowered levels of high density lipoprotein cholesterol, which benefits the heart, and elevated levels of harmful low density lipoprotein, stimulation of prostate tumours, clotting disorders and liver problems. 

Anabolic steroids, antidepressants and drugs of abuse affect libido, potency, and ejaculatory function. Anabolic steroids are derivatives of testosterone, and have strong genitotropic effects. There is published evidence indicating that anabolic steroids increases sexual desire however, the frequency of erectile dysfunction is also increased. Treatment with the antidepressant fluoxetine has been associated with sexual side effects including delayed or nonexistent ejaculation and hyposexuality. Mice treated in utero with the anideukemic agent 5-aza-2/-deoxycytidine exhibit abnormal reproductive behavior and low reproductive capacity. 

Comparison of various halogenated acyl derivatives verifies that the typical properties of the ECD apply also for steroids [355]. Table 5.13 compares the relative retention times and responses of different derivatives of testosterone and cholesterol obtained on... 

In order to prepare the di-HFB derivative of testosterone, reaction in benzene with the addition of pyridine or collidine [360] is recommended, as follows. A 20-jul volume of pyridine or collidine and 10 jul of HFB anhydride are added to 100 jul of a solution of testosterone in benzene (ca. 5 jug/jul). After 2 h at 60°C the mixture is dried under a stream of nitrogen and dissolved in benzene. Under these conditions di-HFB derivative of 2,4-diene-3,17j3-diol is produced as the main product and its amount does not change with time, so that the procedure can be applied for quantitative determination. Less than 30 pg of testosterone can be detected in the form of the di-HFB derivative. 

C26. Culig, Z., Stober, J., Gast, A., Peterziel, H., Hobisch, A., et al., Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone. Cancer Detect. Prevent. 20,68—75 (1996). 

Steroidal O-tetrahydropyran-2-yl derivatives, Ott et al. prepared the 0-tetra-hydropyran-2-yl derivative of testosterone by the reaction of testosterone with 2,3-dihydropyrane catalyzed by p-toluenesulfonic acid monohydrate. The reaction required three weeks and the yield was 59 %. Use of boron trifluoride etherate as catalyst raises the yield to 67% and lowers the reaction time to 10 hr. ... 

Anabolic steroids are synthetic derivatives of testosterone. All have some androgenic activity depending upon their dosage and length of use and are, therefore, also known as anabolic-androgenic steroids. 

Natural testosterone has poor oral bioavaUabdity because of extensive first-pass hepatic metabolism, and large doses must therefore be taken. To improve oral bioavaUability, alkylated derivatives were formulated. Of these, methyltestosterone and fluoxymesterone are more resistant to hepatic catabolism, and can be taken in smaller daily doses, which are potentially safer. However, oral alkylated derivatives of testosterone are associated with a higher incidence of serious hepatotoxicity, and therefore are not preferred for management of sexual dysfunction. 

Intramolecular cyclisation of the 6a-acetamido-derivatives of testosterone acetate and progesterone occurs with sodium hydride in refluxing xylene to afford the corresponding pyrrolo-compounds analogous to the 6a-acetoxy-compounds described above. 

Because of these side effects, researchers have developed compounds that produce the same effects as those obtained from natural testosterone, but without the compound s harmful side effects. Some of those compounds increase the natural production of testosterone in the body when they are ingested. Others are derivatives of testosterone, compounds with similar chemical structures, but minor changes that reduce side effects. These derivatives include compounds such as dihydrotestosterone, androstenedione (also known as andro), dehy-droepiandrosterone (DHEA), clostebol, and nandrolone. Today most derivatives of testosterone and testosterone-producing compounds are banned by sports organizations, both because of their harmful side effects and because of the unfair advantages they provide athletes who use them. 

There are, in fact, quite a few improtant derivatives of testosterone that have been used extensively in therapy and these are summarized in Table 23.1. 

Ethisterone (Fig. 46.14), a 17a-ethynyl derivative of testosterone, is one of the first synthetic progestins to be used therapeutically. In 1937, this agent was synthesized from male sex hormones (androstanes) in an attempt to find an orally active androgen (53). Ethisterone later proved to be an effective oral progestin and became useful in the treatment of menstrual dysfunctions (49). Several molecular modifications... 

Precautions A possible carcinogenic (causes cancer). May be teratogenic (abnormal fetal development) and causes reproductive (infertility, or sterility, or birth defects) effects. Anabolic steroids are synthetic derivatives of testosterone (male hormone). They have beneficial medical benefits when used appropriately for senility, debilitating illness, and for certain convalescents. They are much abused by athletes and can cause serious harmful effects. 

A year previously, Burstein, Dorfman and Nadel [40] had found that metabolic deactivation of hydrocortisone in man occurred through 6/S-hydroxylation. It occurred to the reviewer that such metabolic deactivation might be prevented by 6-methylation. To this end 6a-methylethisterone was prepared by Adams, Ellis, Petrow and Stuart-Webb [41] and found [42] to be c. 6-5 times more potent than the parent ethisterone (XVI) in the Clauberg assay (p. 183). Extending the series. Barton, Bum, Cooley, Ellis, Petrow and Stuart-Webb [43] prepared dimethisterone (XXIV), which is the only derivative of testosterone presently in use. In addition, (XXIV) is surprisingly effective in endometrial carcinoma [44]. 

For drug therapy, native hormones have been replaced to a large extent by synthetic or semisynthetic derivatives that possess higher and more selective therapeutic potential. Some very important synthetic androgen analogs are the esters and the 17-methyl derivative of testosterone. Of the numerous related anabolic steroids, the esters of nandrolone (19-nortestosterone), methandienone (17a-methyl-17-hydroxy-l,4-androstadien-3-one), stanozolol (17a-methyl-2 H-5a-androst-2-eno[3,2-c]pyrazol-17-ol, and trenbolone acetate (17)S-hydroxy-4,9,ll-estratrien-3-one acetate) are most frequently used. 

An active, water-soluble, immobilized form of glucoamylase was obtained when the enzyme reacted with derivatives of testosterone. Highly-charged, water-soluble conjugates of glucoamylase and a copolymer of either ethylene and maleic acid or styrene and maleic acid are absorbed onto particles of DEAE-cellulose to give immobilized derivatives of the enzyme. ... 

Some of the physiological effects of testosterone are to increase muscle mass and decrease body fat. Derivatives of testosterone called anabolic steroids that enhance these effects have been synthesized. Although they have some medical uses, anabolic steroids have been used in high dosages by some athletes in an effort to increase muscle mass. Such use is banned by most sports organizations. 

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