Chemistry of New Steroidal Antiandrogens and 5α-Reductase: 16β-methyl-17α-propionyloxypregna-4,6-diene-3,20-dione

Departamento de Bioquimica, Instituto de Quimica, Universidad Nacional Autonoma de Mexico
â—‹MANUEL SORIANO Eugene Bratoeff

Benign prostatic hyperplasia and prostate cancer are androgen-dependent diseases which afflict a large percentage of males over the age of fifty and are usually treated by surgery. Dihydrotestosterone, a 5alpha-reductase metabolite of testosterone, has been implicated as a causative factor in the progression of these diseases. It has also been determined that dihydrotestosterone interacts more efficiently with the androgen receptors than testosterone This fact indicates that the logical step in the treatment of these diseases should be the inhibition of the 5alpha-reductase enzyme or the blockage of the dihydrotestosterone-receptor formation. Crystals of 16beta-methyl-17alpha-propionyloxypregna-4,6-diene-3,20-dione are orthorhombic and space group P212121. The unit-cell dimensions are a = 7.397(1), b = 11.061(1), c = 27.266(3), V = 2230.7(5)3, Dx = 1.187 g/cm3, and Z = 4. The molecule consists of three six-membered rings and one five-membered ring, all trans fused. The six-membered rings A, B and C occur in a distorted envelope, a distorted half chair and a chair conformations, respectively. Ring D occurs in a conformation between an envelope and a half chair. The bond lengths and angles are normal. The stereochemistry of the title compound is as follows: C8-betaH is trans to C9-alphaH; C9-alphaH is trans to C10-betaCH3; C13-betaCH3 is trans to C14-alphaH; C13-betaCH3 is cis to C17-alpha(COCH3); and C16-betaCH3 is trans to C17-alpha[OCO(CH2)3CH2Br]. The molecules in the crystal are packed at normal van der Waals distances.
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