4-Azasteroidal 5a-reductase inhibitors without affinity forthe androgen receptor

[Παναγιωτης]

In efforts to develop potent 5 alpha-reductase inhibitors without affinity for the androgen receptor, synthetic 3-oxo-5 alpha-steroids were tested for their ability to inhibit 5 alpha-reductase, using [14C]testosterone as the substrate, and for their ability to inhibit the binding of [3H]5 alpha-dihydrotestosterone to the androgen receptor of rat prostate cytosol. 2',3' alpha-Tetrahydrofuran-2'-spiro-17-(5 alpha-androstan-3-one) is not an inhibitor of 5 alpha-reductase and has a high affinity for the androgen receptor; substitution of the -CH2- at the 4-position with N-H resulted in a good inhibitor of 5 alpha-reductase. The 4-N-CH3 derivative is even more active, whereas the N-CH2-CH3 derivative is inactive. These 4-aza derivatives have much lower affinity for the androgen receptor than the parent compound. The 4-N-H derivatives of several 3-oxo-5 alpha-steroids were found to be 20-100% as potent as their corresponding 4-N-CH3 analogs as inhibitors of 5 alpha-reductase, whereas their androgen receptor affinities were at least 40-fold lower than their 4-N-CH3 analogs. Their 5 beta-isomers did not inhibit either 5 alpha-reductase or the androgen receptor binding of [3H]5 alpha-dihydrotestosterone. Two of these 4-N-H steroids, 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one and 17 beta-N, N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, are potent 5 alpha-reductase inhibitors with Ki values equal to 29.2 +/- 1.7 and 12.6 +/- 0.8 nM, respectively, but have little affinity for the androgen receptor. The inhibition of 5 alpha-reductase by both compounds is competitive with testosterone. When [3H]testosterone was incubated with minced rat prostate in the presence of either of these two 4-azasteroids, the nuclear concentration of 5 alpha-dihydrotestosterone decreased and that of testosterone increased. The total nuclear uptake of testosterone plus 5 alpha-dihydrotestosterone was not significantly affected. These 4-azasteroids should be useful for investigating the importance of 5 alpha-reductase in androgen action in vivo.

πηγη

 

[temponeras]

Απ: 4-Azasteroidal 5a-reductase inhibitors without affinity forthe androgen receptor

Δεν περιμενα να το διαβασω ολο αυτο.. παντως με τον τιτλο καταλαβαινει κανεις οτι προσπαθουν να εμποδισουν την ενωση της τεστοστερονης με το ενζυμο 5a-reductase για να αποτραπει η δημιουργια της διυδροτεστοστερονης και ολα αυτα χωρις να επηρεαζει τα ανδρογονα. Δηλαδη μιλαμε για μηδενισμο των πιθανων 'side-effect' και κατα ποσο % θα μπλοκαρει το ενζυμο 5α, γτ αν ειναι νομιζω πως η φινα αυτο κανει κατα μεγαλο ποσοστο.


Αν κανω λαθος ας με διορθωσει καποιος..

 

[Παναγιωτης]

Απ: 4-Azasteroidal 5a-reductase inhibitors without affinity forthe androgen receptor

ναι καπως ετσι
φυσικα και δεν μιλαμε για μηδενισμο των sides
απλα θελουν να μην επηρεαστουν οι ανδρογονοι υποδοχεις

σε λιγους μηνες πιστευω να αρχισουμε να αλλαζουμε σιγα σιγα τα τοπικα