Steroidal androgen biosynthesis inhibitors

Abstract

Androgen Biosynthesis Inhibitors between 0(2) and H(l) and a H bond type linkage (albeit a strong one) between 0(3) and H(l).The very strong interactions of this arrangement are partially relieved in 2 ways. As in the KHMal, KHClMal, and maleic acid structures the internal angles of the ring system are strained considerably. The two angles 0(2)-C(l)-C(2) and 0(3)-C(4)-C(3) are not significantly different from each other and average 119°36' ± 42'. Similarly the angles C(l)-C(2)-C(3) and C(2)-C(3)-C(4) are insignificantly different and average 130°24' ± 24'. These angles are however significantly different from their unstrained counterparts of 121°18' and 121°3 0', respec-

PRODUCTION OF MALE PSEUDOHERMAPHRODITISM IN RATS BY TWO NEW INHIBITORS OF STEROID 17α-Hydroxylase AND C 17-20 LYASE

“…Moreover, other hydroxylases are also affected by these agents. Thus, the synthetic steroidal biosynthesis inhibitors, having no hormonal effects (Arth et al 1971), are not toxic, do not affect other hydroxylases and are more specific testosterone-depriving agents than have been available hitherto. The present finding that inhibitor II administered to male rat pups produces defects in the target organs in adulthood also suggest that these inhibitors can be used to study programming defects in a reversible fashion as compared with neonatal orchidectomy.…”

“…Inhibitor I (16/?-bromo-3/?,17a-dihydroxy-5a-pregnane-ll,20-dione) was purchased from Steraloids, Pawling, New York; inhibitor II (17/?-ureido-l,4-androstadien-3-one) was prepared by Dr G. Arth, Merck & Company, Rahway, N.J. (Arth, Patchett, Jefopoulus, Buglianesi, Peterson, Ham, Kuchl & Brink, 1971). The drugs were tested for purity by thin-layer chromatography and gas-liquid chromatography before use and all were found to be free of contaminants (Goldman & Klingele, 1974).…”

The role of CYP17A1 in prostate cancer development: structure, function, mechanism of action, genetic variations and its inhibition

“…3; Arth et al 1971). Generally, CYP17A1 inhibitors have been structurally categorized as steroidal or non-steroidal.…”

Paradigm Shift in the Concept of Hormonal Milieu of Prostate Cancer

“…[80,81] As the critical catalytic step in all androgen biosynthesis, therapeutic CYP17A1 inhibition to treat prostate cancer and other androgen dependent diseases has been envisioned for over 50 years, with recent discoveries in prostate cancer pathology driving much of the current refocus on CYP17A1 as a therapeutic target. [82,83] Additionally, some evidence suggests that CYP17A1 mRNA and protein expression correlate with disease stage and relapse. [84,85] Despite the strong rational for targeting CYP17A1, this target has been largely unexploited with relatively few inhibitors progressing to clinical trials and only ketoconazole, an unspecific inhibitor of CYP17A1, in widespread clinical use.…”