425-51-4Relevant articles and documents
Crystal structure and synthesis of 17α-Acetoxy-pregn-4,6-diene-3,20- dione
Soriano-Garcia, Manuel,Zambrano, Armando,Cabeza, Marisa,Bratoeff, Eugene
, p. 1115 - 1118 (2010)
17α-Acetoxy-pregn-4,6-diene-3,20-dione (1), C23H 30O4, was synthesized from the commercially available 17α-acetoxyprogesterone. X-ray diffraction analysis of (1) demonstrated that it consists of four rings, three six-membered rings (A, B and C) and one-five-membered ring (D). A, B, C and D rings occur in an envelope; half chair and chair; and half chair conformations, respectively. The crystal of 17α-acetoxy-pregn-4,6-diene-3,20-dione is in orthorhombic crystal system with space group P212121, lattice constants: a = 10.843(1), b = 11.744(1), c = 15.815(2)A, V = 2013.9(4) A3, Dx = 1.222 g/cm3 and Z = 4. The molecules in the crystal are stabilized by C-H???O interactions and van der Waals forces. Graphical Abstract: 17α-acetoxy-pregn-4,6-diene-3,20-dione (1) was synthesized. Compound 1 exhibited a high antiandrogenic effect and could be considered as a potential drug for the treatment of prostate cancer. The crystal structure of (1) was obtained by determination of X-ray diffraction from suitable single crystals. [Figure not available: see fulltext.]
Novel C-6 substituted and unsubstituted pregnane derivatives as 5α-reductase inhibitors and their effect on hamster flank organs diameter size
Cabeza, Marisa,Zambrano, Armando,Heuze, Ivonne,Carrizales, Erick,Palacios, Anay,Segura, Tania,Valencia, Norma,Bratoeff, Eugene
experimental part, p. 793 - 802 (2009/12/01)
The present study is addressed to ascertain the inhibitory effect of several progesterone derivatives having a chlorine substituent at C-6 (12a-12d), 15 with a bromine substituent at C-6 and 14a-14d, without any halogen atom at C-6 all having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom at C-4 position of the phenyl ring) on the 5α-reductase enzyme activity present in human prostate. In addition, it was also of interest to investigate the pharmacological effect on hamster flank organs diameter size. In order to study the structure-activity relationships of steroids 12a-12d, 14a-14d and 15 we determined the concentration of these steroids that inhibited 50% of the activity of human prostate 5α-reductase enzyme (IC50), as well as the in vivo effect of these compounds in the hamster flank organs diameter size. We also ascertained, the capacity of these steroids to bind to the androgen receptors present in the rat prostate cytosol using labeled mibolerone (MIB) for monitoring the binding to the androgen receptor. The results from this study indicated that compounds 12a-12d (having a chlorine substituent at C-6), 14a-14d (lacking a halogen atom at C-6), 13 and 15 (having a bromine atom at C-6) showed an increased antiandrogenic effect (lower value for the diameter of the flank organs) as compared to the flank organs from testosterone-treated hamsters. On the other hand, the series of compounds containing a chlorine substituent at C-6 compounds (12a-12d) showed a higher antiandrogenic activity as compared to the compounds lacking a halogen atom at C-6 (14a, 14b and 14d). Although compounds 13 and 15 decreased the flank organs diameter size, however, this increase was not statistically significant as compared to that of the commercially available product finasteride. The steroidal derivatives 13, 14a-14d (lacking the chlorine substituent at C-6) and 15 (having a bromine atom at C-6) exhibited a higher 5α-reductase inhibitory activity (lower IC50 values) as compared to the series of compounds 12a-12d having the halogen substituent at C-6. Finasteride reduced the diameter size of the flank organs. The effect of this steroid and compounds 12a-12d, 13, 14a-14d and 15 on hamster flank organs can be explained by the fact that these steroids did not bind to the androgens receptor, which indicates that its mechanism of action is an inhibiting for the 5α-reductase activity. This enzyme is present in the hamster flank organs and was inhibited by the novel steroids in the human prostate homogenates.
Bromination of steroidal 3-keto-4,6-diene
Jaime,Reyes,Ruiz,Velez,Mendez,Suarez
, p. 442 - 443 (2007/10/03)
The bromination reaction on 3-keto-4,6-diene steroids, via an epoxide intermediate, with hydrobromic acid in acetic acid medium gives the corresponding 6-bromo derivative. On the other hand, bromination with molecular bromine and subsequent dehydrobromination in an aprotic solvent and basic media afforded the unexpected 4-bromo derivative. In this work we suggest an alternative mechanism for explaining the bromine transposition from C6 to C4.
