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BOMT

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BOMT
Clinical data
Other namesRo 7-2340; 6α-Bromo-4-oxa-17α-methyl-5α-dihydrotestosterone; 6α-Bromo-4-oxa-17α-methyl-5α-androstan-17β-ol-3-one
Routes of
administration		By mouth
Drug classSteroidal antiandrogen
ATC code
  • None
Identifiers
  • (1S,3aS,3bR,5S,5aS,9aR,9bS,11aS)-5-Bromo-1-hydroxy-1,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydroindeno[5,4-f]chromen-7-one
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H29BrO3
Molar mass385.342 g·mol−1
3D model (JSmol)
  • CC12CCC(=O)OC1C(CC3C2CCC4(C3CCC4(C)O)C)Br
  • InChI=1S/C19H29BrO3/c1-17-7-6-15(21)23-16(17)14(20)10-11-12(17)4-8-18(2)13(11)5-9-19(18,3)22/h11-14,16,22H,4-10H2,1-3H3/t11-,12+,13+,14+,16-,17-,18+,19+/m1/s1
  • Key:ZUIGZKIOHUNINA-LWPUPYOYSA-N

BOMT, also known by its developmental code name Ro 7-2340 and as 6α-bromo-4-oxa-17α-methyl-5α-dihydrotestosterone, is a synthetic steroidal antiandrogen which was first produced in 1970 and was never marketed for medical use.[1][2][3][4] It is the 6α-brominated, 4-oxygenated, and 17α-methylated derivative of the androgen dihydrotestosterone (DHT). Along with benorterone, cyproterone (and its C17α acetate ester, cyproterone acetate), and flutamide,[5] BOMT was among the earliest antiandrogens to be developed and extensively studied,[2][3][6][7] although it is less well-documented in comparison to the others.[8] BOMT has been investigated clinically in the treatment of benign prostatic hyperplasia, though development for this use did not continue.[9] There was also interest in BOMT for the potential applications of acne, pattern hair loss, and possibly prostate cancer, but it was not developed for these indications either.[10]

BOMT is a selective competitive antagonist of the androgen receptor (AR),[3][4][11][12][13] although it is described as an "only relatively weak competitor."[14] The relative binding affinity of the drug for the androgen receptor is about 2.7% of that of metribolone.[15] BOMT shows no androgenic, estrogenic, or progestogenic activity even at high doses, nor any inhibition of 5α-reductase,[16] though it has been reported to possess weak antigonadotropic effects.[3][4][11][12] Due to its selectivity for and competitive inhibition of the AR, BOMT has been described as a pure or "true" antiandrogen, similarly to benorterone, cyproterone, and flutamide.[17] Like other steroidal antiandrogens, BOMT may actually be a weak partial agonist of the AR, as it appears to have the potential for weak androgenic effects in specific situations.[18] On the basis of animal research, BOMT does not appear to act as an AR antagonist in central nervous system tissues, and in relation to this, does not disinhibit the hypothalamic–pituitary–gonadal axis or increase testosterone levels.[19]

See also

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References

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  1. ^ Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 178–. ISBN 978-1-4757-2085-3.
  2. ^ a b Boris A, Uskoković M (January 1970). "A new antiandrogen, 6alpha-bromo-17 beta-hydroxy-17 alpha-methyl-4-oxa-5 alpha-androstan-3-one". Experientia. 26 (1): 9–10. doi:10.1007/BF01900355. PMID 5412314. S2CID 39460337. [It is shown that 6α-bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstan-3-one, has significant anti-androgenic activity. Isomers of this compound with different configuration at C-5 and C-6 were found to be inactive.]
  3. ^ a b c d Boris A, DeMartino L, Trmal T (April 1971). "Some endocrine studies of a new antiandrogen, 6-alpha-bromo-17-beta-hydroxy-17-alpha-methyl-4-oxa-5-alpha-androstan-3-one (BOMT)". Endocrinology. 88 (4): 1086–1091. doi:10.1210/endo-88-4-1086. PMID 5542403.
  4. ^ a b c Mangan FR, Mainwaring WI (September 1972). "An explanation of the antiandrogenic properties of 6 -bromo-17 -hydroxy-17 -methyl-4-oxa-5 -androstane-3-one". Steroids. 20 (3): 331–343. doi:10.1016/0039-128X(72)90092-X. PMID 5073580.
  5. ^ Mann T, Lutwak-Mann C (6 December 2012). "Antiandrogens". Male Reproductive Function and Semen: Themes and Trends in Physiology, Biochemistry and Investigative Andrology. Springer Science & Business Media. pp. 352–. ISBN 978-1-4471-1300-3.
  6. ^ Mainwaring WI (6 December 2012). The Mechanism of Action of Androgens. Springer Science & Business Media. pp. 10–. ISBN 978-3-642-88429-0.
  7. ^ Bratoeff E, Ramírez E, Murillo E, Flores G, Cabeza M (December 1999). "Steroidal antiandrogens and 5alpha-reductase inhibitors". Current Medicinal Chemistry. 6 (12): 1107–23. doi:10.2174/0929867306666220401180500. PMID 10519917. S2CID 248057720. Several androstane derivatives have also demonstrated an antiandrogenic activity; 17α-methyl-B-nortestosterone 8 was prepared and tested in 1964 for antihormonal activity [43]. Within the next decades, several other androstane analogs were prepared and found to possess antiandrogenic activity [43, 44, 45, 46] including BOMT 9 "figure 2", R2956 10, SC9420 11, and oxendolone 12 "figure 3".
  8. ^ Clark CR, Nowell NW (April 1979). "Binding properties of testosterone receptors in the hypothalamic-preoptic area of the adult male mouse brain". Steroids. 33 (4): 407–426. doi:10.1016/0039-128X(79)90015-1. PMID 442132. S2CID 42014129. However, a less well documented antiandrogen, BOMT possesses the ideal characteristics of negligible androgenic, estrogenic and progestational activity (55) and would therefore appear to be a valuable compound for use in future investigations.
  9. ^ Kent J, Bischoff A, Herr H, O'Connell W (1973), Study of antiandrogen (Ro–7–2340) (6α-bromo-17β-methyl-4-oxa-5α-andronstan-3-one) in benign prostatic hypertrophy
  10. ^ Mainwaring WI, Mangan FR, Wilce PA, Milroy EG (1973). "Androgens I. — A Review of Current Research on the Binding and Mechanism of Action of Androgenic Steroids, Notably 5α-Dihydrotestosterone". Receptors for Reproductive Hormones. Advances in Experimental Medicine and Biology. Vol. 36. pp. 197–231 (208). doi:10.1007/978-1-4684-3237-4_10. ISBN 978-1-4684-3239-8. PMID 4368414.
  11. ^ a b Setchell BP (1978). The mammalian testis. P. Elek. p. 144. ISBN 978-0-236-31057-9. Another steroidal compound with anti-androgenic activity is BOMT (6α-bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstan-3-one). This compound has no androgenic, oestrogenic or progestational activity but is a potent anti-androgen and (Boris et al., 1970); it competes effectively for the specific, high-affinity binding sites for DHT in the rat prostate (Mangan and Mainwaring, 1972) and depresses testis weight (Boris et al., 1970).
  12. ^ a b King RJ, Mainwaring WI (20 May 2014). Steroid–Cell Interactions. Elsevier. pp. 52, 61, 70–71, 300, 401–403. ISBN 978-1-4831-6510-3.
  13. ^ Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Current Medicinal Chemistry. 7 (2): 211–247. doi:10.2174/0929867003375371. PMID 10637363.
  14. ^ Heyns W, Verhoeven G, De Moor P (May 1976). "Androgen binding in rat uterus cytosol. Study of the specificity". Journal of Steroid Biochemistry. 7 (5): 335–343. doi:10.1016/0022-4731(76)90092-3. PMID 180344. Finally, the steroidal antiandrogen BOMT and the non-steroidal antiandrogen DIMP are only relatively weak competitors.
  15. ^ Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". Journal of Steroid Biochemistry. 15: 355–359. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.
  16. ^ Mangan FR, Mainwaring WI (1971). "The biochemical basis for the antagonism by BOMT of the effects of dihydrotesterone on the rat ventral prostate gland". Gynecologic Investigation. 2 (1): 300–304. doi:10.1159/000301871. PMID 5161490.
  17. ^ Tremblay RR (May 1986). "Treatment of hirsutism with spironolactone". Clinics in Endocrinology and Metabolism. 15 (2): 363–371. doi:10.1016/S0300-595X(86)80030-5. PMID 2941190. Flutamide, cyproterone, benorterone, RU-2956, BOMT and cimetidine are recognized as true antiandrogens because they act as competitive inhibitors of specific ligand binding to androgen receptors.
  18. ^ Ahlin K, Forsberg JG, Jacobsohn D, Thore-Berger B (1975). "The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy". Archives d'Anatomie Microscopique et de Morphologie Expérimentale. 64 (1): 27–44. PMID 1217898.
  19. ^ Clark CR, Nowell NW (August 1979). "BOMT (6 alpha-bromo-17 beta-hydroxy-17 alpha-methyl-4-oxa-5 alpha-androstan-3-one) is not an androgen antagonist within the central nervous system". Steroids. 34 (2): 139–149. doi:10.1016/0039-128X(79)90043-6. PMID 494357. S2CID 54290381.
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