9α-Bromo-11-ketoprogesterone

Last updated
9α-Bromo-11-ketoprogesterone
Braxarone.svg
Clinical data
Synonyms BKP; BOP; NSC-15990; 9α-Bromo-11-oxoprogesterone; Braxarone; Bromo-oxy-progesterone; BOP; 9α-Bromopregn-4-en-3,11,20-trione
Routes of
administration 		By mouth
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
Formula C21H27BrO3
Molar mass 407.35 g·mol−1
3D model (JSmol)

9α-Bromo-11-ketoprogesterone (BKP), or 9α-bromo-11-oxoprogesterone (BOP), also known as braxarone, is an orally active steroidal progestin that was never marketed. [1] [2] [3] [4] It was developed in the 1950s and, along with the testosterone derivatives ethisterone, norethisterone, normethandrone, and norethandrolone and the progesterone derivative hydroxyprogesterone acetate, was one of the first orally active progestogens to be developed. [3] Similarly to various other progestogens, BKP has been studied in the treatment of breast cancer in women. [5] [6] Evaluated in 1959, it was the first oral progestin to be found effective in the treatment of breast cancer. [6] [7] [8]

Oral administration route of administration where a substance is taken through the mouth

Oral administration is a route of administration where a substance is taken through the mouth. Per os (P.O.) is sometimes used as an abbreviation for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example.

Steroid any organic compound having sterane as a core structure

A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes which alter membrane fluidity; and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol (opisthokonts) or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.

Progestin Steroidal compounds related to progesterone, the major mammalian progestational hormone

A progestin (P) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestins are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration.

Whereas 11-ketoprogesterone and 11β-hydroxyprogesterone are virtually devoid of progestogenic 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. [9] [10] In contrast, 9α-fluoro-11β-hydroxyprogesterone has much lower progestogenic activity with only about 8 times that of 11β-hydroxyprogesterone. [10] In addition, whereas 9α-fluoro-11β-hydroxyprogesterone has pronounced mineralocorticoid effects, BKP lacks such effects. [3]

Progestogen

Progestogens, also sometimes written progestagens or gestagens, are a class of steroid hormones that bind to and activate the progesterone receptor (PR). Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintaining pregnancy, although they are also present at other phases of the estrous and menstrual cycles.

Mineralocorticoid A group of corticosteroids primarily associated with water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is its

Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances. The primary mineralocorticoid is aldosterone.

See also

Flugestone

Flugestone, also known as flurogestone, as well as 9α-fluoro-11β,17α-dihydroxyprogesterone, is a steroidal progestin of the 17α-hydroxyprogesterone group that was never marketed. An acetate ester, flurogestone acetate, is used in veterinary medicine.

Fluorometholone chemical compound

Fluorometholone, also known as 6α-methyl-9α-fluoro-11β,17α-dihydroxypregna-1,4-diene-3,20-dione, is a synthetic glucocorticoid which is used in the treatment of inflammatory eye diseases. The C17α acetate ester, fluorometholone acetate, is also a glucocorticoid and is used for similar indications. Specifically, it is indicated for use in the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye.

Haloprogesterone chemical compound

Haloprogesterone, sold under the brand name Prohalone, is a progestin medication which was previously marketed by Ayerst but is now no longer available.

Related Research Articles

Desogestrel chemical compound

Desogestrel, sold under the brand names Cerazette and Mircette among many others, is a progestin medication which is used in birth control pills for women. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.

Dydrogesterone chemical compound

Dydrogesterone, sold under the brand name Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone therapy. It is taken by mouth.

Ethisterone chemical compound

Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecological disorders but is now no longer available. It was used alone and was not formulated in combination with an estrogen. The medication is taken by mouth.

Hydroxyprogesterone caproate chemical compound

Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication which is used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological disorders. It is also used in combination with an estrogen as a form of long-lasting injectable birth control. It is not effective by mouth and must be given by injection into muscle, typically once per week.

Dimethisterone chemical compound

Dimethisterone, formerly sold under the brand names Lutagan and Secrosteron among others, is a progestin medication which was used in birth control pills and in the treatment of gynecological disorders but is now no longer available. It was used both alone and in combination with an estrogen. It is taken by mouth.

Medrogestone chemical compound

Medrogestone, sold under the brand name Colprone among others, is a progestin medication which has been used in menopausal hormone therapy and in the treatment of gynecological disorders. It is available both alone and in combination with an estrogen. It is taken by mouth.

Promegestone chemical compound

Promegestone, sold under the brand name Surgestone, is a progestin medication which is used in menopausal hormone therapy and in the treatment of gynecological disorders. It is taken by mouth.

19-Norprogesterone chemical compound

19-Norprogesterone, also known as 19-norpregn-4-ene-3,20-dione, is a steroidal progestin and close analogue of the sex hormone progesterone, lacking only the C19 methyl group of that molecule. It was first synthesized in 1944 in the form of a mixture that also included unnatural stereoisomers of progesterone, and this mixture was found to be at least equivalent to progesterone in terms of progestogenic activity. Subsequent investigations revealed that 17-isoprogesterone and 14-iso-17-isoprogesterone are devoid of progestogenic activity. 19-Norprogesterone was resynthesized in 1951 with an improved method, and was confirmed to be the component of the mixture synthesized in 1944 that was responsible for its progestogenic activity. In 1953, a paper was published showing that 19-norprogesterone possessed 4- to 8-fold the activity of progesterone in the Clauberg assay in rabbits, and at the time of this discovery, 19-norprogesterone was the most potent progestogen known.

Hydroxyprogesterone acetate chemical compound

Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine.

20α-Dihydroprogesterone chemical compound

20α-Dihydroprogesterone (20α-DHP), also known as 20α-hydroxyprogesterone (20α-OHP), is a naturally occurring, endogenous progestogen. It is a metabolite of progesterone, converted by the 20α-hydroxysteroid dehydrogenases AKR1C1 and AKR1C3, and is still active as a progestogen. However, it is much less potent in comparison, with about one-fifth of the progestogenic activity of progesterone. It has been found to act as an aromatase inhibitor and to inhibit the production of estrogen in breast tissue in vitro.

Norgesterone chemical compound

Norgesterone, also known as norvinodrel or vinylestrenolone and sold under the brand name Vestalin, is a progestin medication which was formerly used in birth control pills for women but is now no longer marketed. It was used in combination with the estrogen ethinylestradiol. It is taken by mouth.

Progestogen ester

A progestogen ester is an ester of a progestogen or progestin. The prototypical progestogen is progesterone, an endogenous sex hormone. Esterification is frequently employed to improve the pharmacokinetics of steroids, including oral bioavailability, lipophilicity, and elimination half-life. In addition, with intramuscular injection, steroid esters are often absorbed more slowly into the body, allowing for less frequent administration. Many steroid esters function as prodrugs.

17α-Methylprogesterone chemical compound

17α-Methylprogesterone (17α-MP), or 17α-methylpregn-4-ene-3,20-dione, is a steroidal progestin related to progesterone that was synthesized and characterized in 1949 but was never marketed. Along with ethisterone (1938) and 19-norprogesterone (1951), 17α-MP was one of the earliest derivatives of progesterone to be identified as possessing progestogenic activity. Similarly to progesterone and derivatives like 17α-hydroxyprogesterone and 19-norprogesterone, 17α-MP was found to possess poor oral bioavailability, but showed improved progestogenic activity relative to progesterone when administered via other routes. In addition to its activity as a progestogen, 17α-MP has also been found to possess some antiglucocorticoid activity.

11-Ketoprogesterone chemical compound

11-Ketoprogesterone, or 11-oxoprogesterone, also known as pregn-4-ene-3,11,20-trione, is a pregnane steroid related to cortisone (11-keto-17α,21-dihydroxyprogesterone) that was formerly used in veterinary medicine in the treatment of bovine ketosis. It was synthesized in 1940. The steroid has profound effects on carbohydrate metabolism and possesses activities associated with adrenal cortex hormones like cortisone. However, it is non-toxic even in high dosages, suggesting that it lacks conventional glucocorticoid activity, and it does not possess mineralocorticoid activity, unlike other adrenocortical hormones. 11-Ketoprogesterone may act through membrane glucocorticoid receptors.

Progesterone 3-acetyl enol ether chemical compound

Progesterone 3-acetyl enol ether, also known as progesterone acetate, as well as 3-acetoxypregna-3,5-dien-20-one, is a progestin which was never marketed. It was reported to possess similar potency to progesterone and hydroxyprogesterone caproate in the rabbit endometrial carbonic anhydrase test, a bioassay of progestogenic activity. In addition, it was able to maintain pregnancy in animals. Progesterone 3-acetyl enol ether is closely related to quingestrone, which is also known as progesterone 3-cyclopentyl enol ether and was formerly marketed as an oral contraceptive.

DU-41164 chemical compound

DU-41164, also known as 1,2β-methylene-6-fluoro-17α-acetoxy-δ6-retroprogesterone, is a progestin which was developed by Philips-Duphar in the 1970s and was never marketed. It is a combined derivative of 17α-hydroxyprogesterone and retroprogesterone. The drug shows extremely high potency as a progestogen in animals; it was reported to possess 500 times the affinity of progesterone for the progesterone receptor expressed in rabbit uterus, and showed 600 times the progestogenic potency of subcutaneous progesterone when given orally in animals. The affinity of DU-41164 for the progesterone receptor was described in 1974 as "probably the highest reported for any steroid-receptor interaction". The drug showed no androgenic, anabolic, antiandrogenic, estrogenic, or corticosteroid activity in animals. Although highly potent in animals, DU-41164 produced little or no progestogenic effect at dosages of 50 and 200 µg/day in women, suggesting major species differences. A closely related compound, DU-41165, has been developed as a photoaffinity label for the progesterone receptor.

The pharmacology of progesterone, a progestogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

Methenmadinone acetate Progestin

Methenmadinone acetate (MMA), also known as methylenedehydroacetoxyprogesterone (MDAP) and sold under the brand names Superlutin and Antigest, is a progestin medication which was developed in Czechoslovakia in the 1960s. It is the C17α acetate ester of methenmadinone.

References

  1. ↑ Martin Negwer; Hans-Georg Scharnow (2001). Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. p. 2134. ISBN   978-3-527-30247-5.
  2. ↑ TYLER ET, OLSON HJ (1958). "Clinical use of new progestational steroids in fertility". Ann. N. Y. Acad. Sci. 71 (5): 704–9. PMID   13583825.
  3. 1 2 3 WIED GL, DAVIS ME (1957). "9 alpha-Bromo-11-ketoprogesterone; another new orally effective substance with progestational activity". Obstet Gynecol. 10 (4): 411–7. PMID   13477602.
  4. ↑ Tyler, Edward T. (1959). "FERTILITY PROMOTING AND INHIBITING EFFECTS OF NEW STEROID HORMONAL SUBSTANCES". Journal of the American Medical Association. 169 (16): 1843. doi:10.1001/jama.1959.03000330015003. ISSN   0002-9955.
  5. ↑ Alan C. Sartorelli; David G. Johns (27 November 2013). Antineoplastic and Immunosuppressive Agents. Springer Science & Business Media. pp. 185–. ISBN   978-3-642-65806-8.
  6. 1 2 GOLDENBERG IS, HAYES MA (1959). "Hormonal therapy of metastatic female breast carcinoma. I. 9 alpha-Bromo-11-ketoprogesterone". Cancer. 12 (4): 738–40. PMID   13663018.
  7. ↑ Carpenter JT (1988). "Progestational agents in the treatment of breast cancer". Cancer Treat. Res. 39: 147–56. PMID   2908605.
  8. ↑ Kaufman RJ (May 1981). "Advanced breast cancer - additive hormonal therapy". Cancer. 47 (10): 2398–403. PMID   7272894.
  9. ↑ Veterinary Medicine. American Veterinary Publishing Company. 1953. Ketogestin [(11-ketoprogesterone)] is devoid of androgenic, estrogenic, or progestational activity and is nontoxic in amounts greatly exceeding pharmacological dosage.
  10. 1 2 Otto Hoffmann-Ostenhof (1959). Proceedings of the Fourth International Congress of Biochemistry, Vienna, 1-6 September, 1958. and. p. 269. 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.


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