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| Clinical data | |
|---|---|
| Trade names | Braxarone |
| Other names | BKP; BOP; NSC-15990; 9α-Bromo-11-oxoprogesterone; Braxarone; Bromo-oxy-progesterone; BOP; 9α-Bromopregn-4-en-3,11,20-trione; Bromopregnenetrione |
| Routes of administration | By mouth |
| Identifiers | |
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| CAS Number | |
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| ChEBI | |
| Chemical and physical data | |
| Formula | C21H27BrO3 |
| Molar mass | 407.348 g·mol−1 |
| 3D model (JSmol) | |
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Bromoketoprogesterone (BKP), also known as9α-bromo-11-oxoprogesterone (BOP), and known by the tentative brand nameBraxarone (Squibb), is anorally activeprogestin which does not appear to have been marketed.[1][2][3][4][5]
Whereas11-ketoprogesterone and11β-hydroxyprogesterone are virtually devoid ofprogestogenic activity (although 11β-hydroxyprogesterone has been reported to possess about 1% of the progestogenic activity of progesterone), the progestogenic activity of BKP is restored and is in fact relatively high.[6][7] In contrast,9α-fluoro-11β-hydroxyprogesterone has much lower progestogenic activity with only about 8 times that of 11β-hydroxyprogesterone.[7] In addition, whereas 9α-fluoro-11β-hydroxyprogesterone has pronouncedmineralocorticoid effects, BKP lacks such effects.[3]
BKP has been described as a weaker progestogen.[8] It has been used at doses of as much as 300 mgorally per day.[9][8]
In addition to its activity as a progestogen, BKP hasglucocorticoid activity.[9]
Thepharmacokinetics of BKP have been reviewed.[10]
Chemical syntheses of BKP have been published.[10]
It was developed in the 1950s and, along with thetestosterone derivativesethisterone,norethisterone,normethandrone, andnorethandrolone and theprogesterone derivativehydroxyprogesterone acetate, was one of the first orally activeprogestogens to be developed.[3] Similarly to various other progestogens, BKP has been studied in the treatment ofbreast cancer in women.[11][12][9]: 185 Evaluated in 1959, it was the first oral progestin to be found effective in the treatment of breast cancer.[12][13][14][9] It induced regression in 20% of women with advanced breast cancer at a dosage of 300 mg/day orally.[9]
Ketogestin [(11-ketoprogesterone)] is devoid of androgenic, estrogenic, or progestational activity and is nontoxic in amounts greatly exceeding pharmacological dosage.
In addition, it had been previously reported that 11β-hydroxyprogesterone was devoid of progestational action. However, we found that it does possess about 1% of the activity of progesterone. This trace activity is substantially enhanced by fluorination, since 9α-fluoro-11β-hydroxyprogesterone is eight times as active as the non-halogenated analogue.6 Concomitantly, Fried et al.7 described the relatively high progestational activity of 9α-bromo-11-ketoprogesterone as well.
Halogenated progestogens have also been studied in patients with breast cancer. 9α-Bromo-11-oxoprogesterone (bromoketoprogesterone) given in a dose of 300 mg orally daily in patients with advanced breast cancer induced a 20 % regression rate. Regression of cancer occurs mainly in soft tissue and osseous metastases. [...] Both of these progestational compounds possess corticoid activity, particularly oxylone acetate, which, in 50 mg doses, causes Cushingoid symptoms, hypertension, and osteoporosis. On withdrawal of the drug, vaginal bleeding occurs frequently. [...] Progesterone-like compounds with glucocorticoid activity, such as oxylone, induce severe Cushingoid symptoms such as plethora, moonface, glycosuria, marked weight gain, and hypertension, requiring discontinuation of the drug.
