Anti‐prostatic Activity of Bifluranol, a Fluorinated Bibenzyl

Abstract

1Endocrine and anti-fertility studies were carried out on a fluorinated bibenzyl, bifluranol, in rats and mice. 2 A potent anti-prostatic activity of bifluranol was shown to be comparable to diethylstilboestrol (DES). In contrast, its oestrogenic potency by the oral route was about eight times less than that of DES. 3 In comparative short and long-term anti-androgenic and fertility studies in rats and in studies on sexual potency and reproductive performance in male mice, bifluranol given orally was shown to produce fully reversible suppression of accessory sexual structures without impairment of spermatogenesis and fertility. In contrast, DES administered in the same dose reduced spermatogenesis as well as accessory sexual glands. 4 Bifluranol lowered serum luteinising hormone (LH) levels without affecting follicle stimulating hormone (FSH). Under similar conditions DES reduces both LH and FSH levels. Since bifluranol does not antagonize androgen-induced stimulation of the prostate in castrated rats, its anti-prostatic effect is interpreted as a negative, hormonostatic feedback activity, mediated through a selective inhibition of LH secretion.

Enantioselective installation of adjacent tertiary benzylic stereocentres using lithiation–borylation–protodeboronation methodology. Application to the synthesis of bifluranol and fluorohexestrol

“…Having found conditions under which high diastereoselectivity could be achieved, we sought to apply this methodology to the enantioselective synthesis of bifluranol ( 1 ), an antiandrogen with the ability to treat benign prostate enlargement, 2 and fluorohexestrol ( 2 ), a potential non-steroidal oestrogen receptor based imaging agent for the visualisation of human breast tumours. 3 The retrosynthetic analysis of 1 and 2 is illustrated in Scheme 5 .…”

“… 1 For molecules without hydroxyl functionality, 1,2- and 1,3-stereocontrol is much more difficult and general synthetic methods are sparse. This problem is highlighted in the synthesis of the antiandrogen, bifluranol 2 (Prostarex, 1 ), and the potential imaging agent, fluorohexestrol 3 2 (used for the visualisation of human breast tumours), where neither relative nor absolute stereocontrol could be achieved. 4 These rather unusual molecules bear a structural similarity to the hormone estradiol, accounting for their particular biological activity.…”

Bifluranol in the treatment of benign prostatic hyperplasia (BPH)

“…Objective urodynamic measurements are less open to misinterpretation and the significant reduction in residual urine volumes and the improvement in flow rates observed in this study could indicate a beneficial response to treatment with bifluranol. In earlier animal studies, Dekanski [9] found a significant reduction in the weight of the prostate with bifluranol and concluded that the drug was a potent "antiprostatic agent." With the aid of prostate ultrasound, we were unable to detect any change in prostate size.…”

“…1) is a fluorinated bibenzyl antiandrogenic drug with low estrogenic activity. Administration to rats produced a reduction in the weight of the ventral prostate and a lowering of LH without causing infertility or impairment of spermatogenesis [9]. In animal studies bifluranol was found to be less toxic than stilbestrol and this has been attributed to its resistance to metabolic hydroxylation [ 10,111.…”

Bifluranol, a novel fluorinated bibenzyl anti-androgen, its chemistry and disposition in different animal species

“…1967). Bifluranol has been shown to be a comparable antiandrogen to diethylstilboestrol, but in the rat it has only one eighth of the oestrogenic activity of diethylstilboestrol (Dekanski 1980). Bifluranol is currently being evaluated as a treatment for prostatic enlargement in man.…”