Steroidal drugs

Testosterone and six cell tnicrosome metabolites (6j8-, 16a-, 16, 7a-, 2a-hydro-xytestosterone, and androstenedione) were well resolved and eluted in 35 min on a 40°C Cig column (A = 242nm) using a 50/38.5/11.5 water (0.1 mM Na2HP04 at pH 6)/methanol/acetonitrile mobile phase [529]. The authors make special note that the use of THF is to be avoided due to chances of its reactmg with the analytes. Linear ranges of 280-4600 ng/mL for metabolites and 20-40 pg/mL for testosterone were reported. 

Three corticosteroids (dexamethasone, flumethasone, triamcinolone acetonide) were recovered from feedstock and separated on a C g column (A = 242 nm) using a 50/50 methanol/water mobile phase [530], Baseline separation was achieved and elution was complete in 14 min. Detection limits of lOOpg/mL were reported. 

Ethinylestradiol, norgestrel, and norethisterone acetate from tablets were resolved on a j8-cyclodextrin colutim (A = 280 nm) using a 40/60 methanol/water (50 mM phosphate buffer at pH 7.0) mobile phase [531]. Peak shapes were excellent and 25 ng injected was easily detected. 

Hirata et al. [533] developed a method to separate prednisolone, prednisone, cortisol, cortisone, and deflazacort metabolites II III. A C g column (A = 254 nm) and a 10/90 30/70 IPA/water (0.05 M acetate buffer at pH 4.5) gradient gave 

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Drugs of particularly complex structure are often prepared commercially by partial synthesis from some abundant, structurally related, natural product obtained from plants. The majority i)f steroid drugs are in fact prepared in just this way. Prostaglandins are unique in that no prostanoid compounds have yet been found in plants, a perhaps surprising finding in view of the wide distribution of essential fatty acids in plant materials. 

Applezweig, N. Steroid Drugs, Vol. 1, 62 (New York, Toronto, London 1962). 

Hughes, G.S., Francom, S.F., Means, L.K., Bohan, D.F., Caruana, C. and Holland, M. (1992). Synergistic effects of oral non-steroidal drugs and topical corticosteroids in the therapy of sunburn in humans. Dermatology 184, 54—58. 

At Upjohn he became Vice President for Research and a member of the Board of Directors. Shortly after arrival he was told to pick one major area ot research for Upjohn and then to do what was necessary to put Upjohn research in the front ranks of pharmaceutical research. He picked steroids as the area to emphasize, and under his direction Upjohn became a major factor in steroidal drugs and a leader in research. His friends at DuPont were not surprised to hear by the grapevine that Schreiber seemed to know all the Upjohn research people by their first names, was a stimulating leader, and answered his own phone. 

While steroids generated in the brain have been referred to as neurosteroids , another useful term is neuroactive steroids to refer to all steroids that affect brain function via any mechanism and irrespective of site of formation. The term neuroactive steroid also has been used to describe neuroactive steroid drugs. 

As indicated by the aforementioned examples U5-U8>5 the most useful feature of the intramolecular trapping of o-xylylenes generated from benzocyclobutenes is the control of stereochemistry so that high purity of ( )-estrone could be obtained. Subsequent molecular manipulation of synthetic estrone may give rise to alternative routes to other medicinally important steroid drugs. 

P. Pavek, G. Merino, E. Wagenaar, E. Bolscher, M. Novotna, J.W. Jonker, and A.H. Schinkel. Human breast cancer resistance protein Interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-l-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther. 312 144—152... 

A number of steroidal drugs are produced by procedures that include nucleophilic attack of sodium acetylide onto a ketone, particularly that at position 17 on the five-membered ring of the steroid (see Box 3.19). 

Figure 6J8 (a) The chromatogram from a 0.75 mg injection of an impure steroidal drug substance. Peaks 1-5 are at levels of 2-3% each. The individual peaks were stored in BPSU loops, (b) NMR spectra were acquired with NOESY presaturation with an acquisition time of 10 h on a Bruker DRX500 fitted with a 4-mm SEl z-gradient EC probe with a 120 pi active cell volume. 

Androgenic steroids are used in medicine for replacement therapy in men with insufficient function of the male sex glands, for maturation arrest, impotency, climacteric, and other irregularities, and in women for breast and ovarian cancer and climacteric disorders. Like all steroid drugs, androgens are functionalized derivatives of cyclopentanophenan-threne. 

Non-steroidal drug having specific antiandrogen activity. Active metabolite, 2-hydroxyflutamide competitively blocks androgen action on accessory sex organs and pituitary. It leads to increased LH secretion by blocking feedback inhibition. It is used in advanced carcinoma prostate, female hirsutism. 

One commercially important class of steroid drugs, it should be noted, is still, interestingly, obtained by isolation from mammahan sources. The best-known drug... 

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