Hydroxyflutamide

Hydroxyflutamide
Clinical data
Other names	2-Hydroxyflutamide; HF; OHF; Flutamide-hydroxide; SCH-16423; Hydroxyniphtholide; Hydroxyniftolide; α,α,α-Trifluoro-2-methyl-4'-nitro-m-lactotoluidide
Drug class	Nonsteroidal antiandrogen
Identifiers
	IUPAC name 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide;
CAS Number	52806-53-8;
PubChem CID	91649;
IUPHAR/BPS	2862;
ChemSpider	82752;
UNII	31D90UKP5Y;
KEGG	C14204;
ChEBI	CHEBI:43064;
ChEMBL	ChEMBL491;
CompTox Dashboard (EPA)	DTXSID8033562 ;
ECHA InfoCard	100.169.708
Chemical and physical data
Formula	C11H11F3N2O4
Molar mass	292.214 g·mol−1
3D model (JSmol)	Interactive image;
	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. 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.

Affinities
Compound	RBATooltip Relative binding affinity
Metribolone	100
Dihydrotestosterone	85
Cyproterone acetate	7.8
Bicalutamide	1.4
Nilutamide	0.9
Hydroxyflutamide	0.57
Flutamide	<0.0057
Notes: ↑ At androgen receptors; measured in human prostate tissue. ↑ Relative to Metribolone, which is by definition 100%

Relative affinities of first-generation nonsteroidal antiandrogens for the androgen receptor
Species	IC₅₀Tooltip Half maximal inhibitory concentration (nM)			RBATooltip Relative binding affinity (ratio)
Species	Bicalutamide	2-Hydroxyflutamide	Nilutamide	Bica / 2-OH-flu	Bica / nilu	Ref
Rat	190	700	ND	4.0	ND
Rat	~400	~900	~900	2.3	2.3
Rat	ND	ND	ND	3.3	ND
Rat^a	3595	4565	18620	1.3	5.2
Human	~300	~700	~500	2.5	1.6
Human	~100	~300	ND	~3.0	ND
Human^a	2490	2345	5300	1.0	2.1
Footnotes: ^a = Controversial data. Sources: See template.

Relative potencies of selected antiandrogens
Antiandrogen	Relative potency
Bicalutamide	4.3
Hydroxyflutamide	3.5
Flutamide	3.3
Cyproterone acetate	1.0
Zanoterone	0.4
Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c.Tooltip subcutaneous injection testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Higher values mean greater potency. Sources: See template.

[4] At androgen receptors; measured in human prostate tissue.

[6] Relative to Metribolone, which is by definition 100%