BOMT

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
IUPAC name
  • (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)
SMILES
  • CC12CCC(=O)OC1C(CC3C2CCC4(C3CCC4(C)O)C)Br
InChI
  • 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 developed 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][8] although it is less well-documented in comparison to the others.[9] BOMT has been investigated clinically in the treatment of benign prostatic hyperplasia, though development for this use did not continue.[10] 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.[11]

BOMT is a selective competitive antagonist of the androgen receptor (AR),[3][4][12][13][14] although it is described as an "only relatively weak competitor."[15] The relative binding affinity of the drug for the androgen receptor is about 2.7% of that of metribolone.[16] BOMT shows no androgenic, estrogenic, or progestogenic activity even at high doses, nor any inhibition of 5α-reductase,[17] though it has been reported to possess weak antigonadotropic effects.[3][4][12][13] 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.[18] 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.[19] 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.[20]

See also

References

  1. ↑ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 178–. ISBN 978-1-4757-2085-3.
  2. 1 2 Boris, A.; Uskokovic, M. (1970). "A new antiandrogen. 6α-Bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstan-3-one". Experientia. 26 (1): 9–10. doi:10.1007/BF01900355. ISSN 0014-4754. 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. 1 2 3 4 Boris, Alfred; Demartino, Louis; Trmal, Thelma (1971). "Some Endocrine Studies of a New Antiandrogen, 6 α-Bromo-17β-hydroxy-17α-methyl-4-oxa-5α:-androstan-3-one (BOMT)". Endocrinology. 88 (4): 1086–1091. doi:10.1210/endo-88-4-1086. ISSN 0013-7227. PMID 5542403.
  4. 1 2 3 Mangan, F.R.; Mainwaring, W.I.P. (1972). "An explanation of the antiandrogenic properties of 6α-bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstane-3-one". Steroids. 20 (3): 331–343. doi:10.1016/0039-128X(72)90092-X. ISSN 0039-128X. PMID 5073580.
  5. ↑ T. Mann; C. Lutwak-Mann (6 December 2012). 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. ↑ W.I.P. Mainwaring (6 December 2012). The Mechanism of Action of Androgens. Springer Science & Business Media. pp. 10–. ISBN 978-3-642-88429-0.
  7. ↑ Bentham Science Publishers (December 1999). Current Medicinal Chemistry. Bentham Science Publishers. pp. 1110–1111. 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. ↑ Anthony W. Norman; Gerald Litwack (28 June 2014). Hormones. Elsevier Science. pp. 508–. ISBN 978-1-4832-5810-2.
  9. ↑ Clark, C.R.; Nowell, N.W. (1979). "Binding properties of testosterone receptors in the hypothalamic-preoptic area of the adult kale mouse brain". Steroids. 33 (4): 407–426. doi:10.1016/0039-128X(79)90015-1. ISSN 0039-128X. 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.
  10. ↑ John Kent; Arthur Bischoff; Harry Herr & William O'Connell (1973), Study of antiandrogen (Ro–7–2340) (6α-bromo-17β-methyl-4-oxa-5α-andronstan-3-one) in benign prostatic hypertrophy
  11. ↑ Bert O'Malley (11 November 2013). Receptors for Reproductive Hormones. Springer Science & Business Media. pp. 208–. ISBN 978-1-4684-3237-4.
  12. 1 2 Brian Peter Setchell (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 (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).
  13. 1 2 R. J. B. King; W. I. P. Mainwaring (20 May 2014). Steroid–Cell Interactions. Elsevier. pp. 52, 61, 70–71, 300, 401–403. ISBN 978-1-4831-6510-3.
  14. ↑ Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity Relationships" (PDF). Current Medicinal Chemistry. 7 (2): 211–247. doi:10.2174/0929867003375371. ISSN 0929-8673. PMID 10637363.
  15. ↑ Heyns, W.; G., Verhoeven; De Moor, P. (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. ISSN 0022-4731. PMID 180344. Finally, the steroidal antiandrogen BOMT and the non-steroidal antiandrogen DIMP are only relatively weak competitors.
  16. ↑ Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". J. Steroid Biochem. 15: 355–9. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.
  17. ↑ Mangan, F.R.; Mainwaring, W.I.P. (1971). "The Biochemical Basis for the Antagonism hy BOMT of the Effects of Dihydrotesterone on the Rat Ventral Prostate Gland". Gynecologic and Obstetric Investigation. 2 (1–6): 300–304. doi:10.1159/000301871. ISSN 1423-002X. PMID 5161490.
  18. ↑ Tremblay, Roland R. (1986). "10 Treatment of hirsutism with spironolactone". Clinics in Endocrinology and Metabolism. 15 (2): 363–371. doi:10.1016/S0300-595X(86)80030-5. ISSN 0300-595X. 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.
  19. ↑ 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". Arch Anat Microsc Morphol Exp. 64 (1): 27–44. PMID 1217898.
  20. ↑ Clark, C.R.; Nowell, N.W. (1979). "Bomt (6α-bromo-17β-hydroxy-17α-methyl-4-oxa-5α-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. ISSN 0039-128X. PMID 494357. S2CID 54290381.
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