Hydroxyflutamide

Hydroxyflutamide
Clinical data
Other names2-Hydroxyflutamide; HF; OHF; Flutamide-hydroxide; SCH-16423; Hydroxyniphtholide; Hydroxyniftolide; α,α,α-Trifluoro-2-methyl-4'-nitro-m-lactotoluidide
Drug classNonsteroidal antiandrogen
Identifiers
IUPAC name
  • 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.169.708 Edit this at Wikidata
Chemical and physical data
FormulaC11H11F3N2O4
Molar mass292.214 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F)O
InChI
  • InChI=1S/C11H11F3N2O4/c1-10(2,18)9(17)15-6-3-4-8(16(19)20)7(5-6)11(12,13)14/h3-5,18H,1-2H3,(H,15,17)
  • Key:YPQLFJODEKMJEF-UHFFFAOYSA-N

Hydroxyflutamide (HF, OHF) (developmental code name SCH-16423), or 2-hydroxyflutamide, is a nonsteroidal antiandrogen (NSAA) and the major active metabolite of flutamide, which is considered to be a prodrug of hydroxyflutamide as the active form.[1][2] It has been reported to possess an IC50 of 700 nM for the androgen receptor (AR), which is about 4-fold less than that of bicalutamide.[3]

Affinities[lower-alpha 1][4]
Compound RBA[lower-alpha 2]
Metribolone 100
Dihydrotestosterone 85
Cyproterone acetate 7.8
Bicalutamide 1.4
Nilutamide 0.9
Hydroxyflutamide 0.57
Flutamide <0.0057
Notes:
  1. At androgen receptors; measured in human prostate tissue.
  2. Relative to Metribolone, which is by definition 100%
Relative affinities of first-generation nonsteroidal antiandrogens for the androgen receptor
SpeciesIC50 (nM)RBA (ratio)
Bicalutamide2-HydroxyflutamideNilutamideBica / 2-OH-fluBica / niluRef
Rat190700ND4.0ND[5]
Rat~400~900~9002.32.3[6]
RatNDNDND3.3ND[7]
Rata35954565186201.35.2[8]
Human~300~700~5002.51.6[4]
Human~100~300ND~3.0ND[9]
Humana2490234553001.02.1[8]
Footnotes: a = Controversial data. Sources: See template.
Relative potencies of selected antiandrogens
AntiandrogenRelative potency
Bicalutamide4.3
Hydroxyflutamide3.5
Flutamide3.3
Cyproterone acetate1.0
Zanoterone0.4
Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c. testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Sources: See template.

References

  1. Serra, C; Sandor, NL; Jang, H; Lee, D; Toraldo, G; Guarneri, T; Wong, S; Zhang, A; Guo, W; Jasuja, R; Bhasin, S (2013). "The effects of testosterone deprivation and supplementation on proteasomal and autophagy activity in the skeletal muscle of the male mouse: Differential effects on high-androgen responder and low-androgen responder muscle groups". Endocrinology. 154 (12): 4594–606. doi:10.1210/en.2013-1004. PMC 3836062. PMID 24105483.
  2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity Relationships". Current Medicinal Chemistry. 7 (2): 211–247. doi:10.2174/0929867003375371. ISSN 0929-8673. PMID 10637363.
  3. Furr BJ (1995). "Casodex: preclinical studies and controversies". Annals of the New York Academy of Sciences. 761 (3): 79–96. Bibcode:1995NYASA.761...79F. doi:10.1111/j.1749-6632.1995.tb31371.x. PMID 7625752. S2CID 37242269.
  4. 1 2 Ayub M, Levell MJ (August 1989). "The effect of ketoconazole related imidazole drugs and antiandrogens on [3H] R 1881 binding to the prostatic androgen receptor and [3H]5 alpha-dihydrotestosterone and [3H]cortisol binding to plasma proteins". J. Steroid Biochem. 33 (2): 251–5. doi:10.1016/0022-4731(89)90301-4. PMID 2788775.
  5. Furr BJ, Valcaccia B, Curry B, Woodburn JR, Chesterson G, Tucker H (June 1987). "ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen". J. Endocrinol. 113 (3): R7–9. doi:10.1677/joe.0.113R007. PMID 3625091.
  6. Teutsch G, Goubet F, Battmann T, Bonfils A, Bouchoux F, Cerede E, Gofflo D, Gaillard-Kelly M, Philibert D (January 1994). "Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor". J. Steroid Biochem. Mol. Biol. 48 (1): 111–9. doi:10.1016/0960-0760(94)90257-7. PMID 8136296.
  7. Winneker RC, Wagner MM, Batzold FH (December 1989). "Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist". J. Steroid Biochem. 33 (6): 1133–8. doi:10.1016/0022-4731(89)90420-2. PMID 2615358.
  8. 1 2 Luo, S; Martel, C; LeBlanc, G; Candas, B; Singh, S M; Labrie, C; Simard, J; Belanger, A; Labrie, F (1996). "Relative potencies of Flutamide and Casodex: preclinical studies". Endocrine Related Cancer. 3 (3): 229–241. doi:10.1677/erc.0.0030229. ISSN 1351-0088.
  9. Kemppainen JA, Wilson EM (July 1996). "Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen receptor stabilization". Urology. 48 (1): 157–63. doi:10.1016/S0090-4295(96)00117-3. PMID 8693644.


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