RU-58841

RU-58841, also known as PSK-3841 or HMR-3841, is a nonsteroidal antiandrogen (NSAA) which was initially developed in the 1980s. It was formerly under investigation by ProStrakan (previously ProSkelia and Strakan) for potential use as a topical treatment for androgen-dependent conditions including acne, pattern hair loss[1], and excessive hair growth.[2][3][4][5] The compound is similar in structure to the NSAA RU-58642 but contains a different side-chain.[6] These compounds are similar in chemical structure to nilutamide,[7] which is related to flutamide, bicalutamide, and enzalutamide, all of which are NSAAs similarly.[8] RU-58841 can be synthesized either by building the hydantoin moiety or by aryl coupling to 5,5-dimethylhydantoin.[9]

RU-58841

Clinical data
Other names	PSK-3841; HMR-3841
Drug class	Nonsteroidal antiandrogen
Identifiers
IUPAC name 4-[3-(4-Hydroxybutyl)-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl]-2-(trifluoromethyl)benzonitrile
CAS Number	154992-24-2
PubChem CID	132981
ChemSpider	117358
UNII	0D8FJQ0ADW
ChEMBL	ChEMBL9337
CompTox Dashboard (EPA)	DTXSID20165781
Chemical and physical data
Formula	C17H18F3N3O3
Molar mass	369.344 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CC1(C(=O)N(C(=O)N1CCCCO)C2=CC(=C(C=C2)C#N)C(F)(F)F)C
InChI InChI=1S/C17H18F3N3O3/c1-16(2)14(25)23(15(26)22(16)7-3-4-8-24)12-6-5-11(10-21)13(9-12)17(18,19)20/h5-6,9,24H,3-4,7-8H2,1-2H3 Key:ARBYGDBJECGMGA-UHFFFAOYSA-N

RU-58841 produces cyanonilutamide (RU-56279) and RU-59416 as metabolites in animals.[10] Cyanonilutamide has relatively low affinity for the androgen receptor but shows significant antiandrogenic activity in animals.[10] RU-59416 has very low affinity for the androgen receptor.[10]

Affinities of a selection of androgen receptor
ligands at steroid hormone receptors

Compound	AR	ER	PR	GR	MR
Metribolone	290	< 0.1	190	4	38
Dihydrotestosterone	180	?	?	?	?
Testosterone	100	?	?	?	?
Cyproterone acetate	10	?	?	?	?
Bicalutamide	1.8	?	?	?	?
Nilutamide	0.8	?	?	?	?
Hydroxyflutamide	0.8	?	?	?	?
RU-59063	300	<0.1	<0.1	<0.1	<0.1
RU-58841	150	?	?	?	?
RU-58642	46	<0.1	<0.1	<0.1	<0.1
RU-57073	163	<0.1	<0.1	<0.1	<0.1
RU-56187	92	<0.1	<0.1	<0.1	<0.1
Notes: Values are RBAs (%). Reference ligands (100%) were testosterone for the AR, estradiol for the ERα and ERβ, progesterone for the PR, dexamethasone for the GR, and aldosterone for the MR. Sources: See template.

See also

• Cyanonilutamide
• RU-56187
• RU-57073
• RU-58642
• RU-59063

References

1. "RU58841 studies and information". Anagen.
2. PSK-3841 (HMR-3841, RU-58841) - AdisInsight
3. Battmann T, Bonfils A, Branche C, Humbert J, Goubet F, Teutsch G, Philibert D (January 1994). "RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism". J. Steroid Biochem. Mol. Biol. 48 (1): 55–60. doi:10.1016/0960-0760(94)90250-X. PMID 8136306.
4. Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis C, Blume-Peytavi U, Schäfer-Korting M (January 2005). "RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia". Pharmazie. 60 (1): 8–12. PMID 15700772.
5. "RU58841 for Hair Loss – Underused Finasteride Alternative?". Hairverse. 2019-03-10. Retrieved 2020-07-14.
6. Van Dort ME, Jung YW (April 2001). "Synthesis and structure-activity studies of side-chain derivatized arylhydantoins for investigation as androgen receptor radioligands". Bioorg. Med. Chem. Lett. 11 (8): 1045–7. doi:10.1016/s0960-894x(01)00146-9. PMID 11327585.
7. Poulos GA, Mirmirani P (February 2005). "Investigational medications in the treatment of alopecia". Expert Opin Investig Drugs. 14 (2): 177–84. doi:10.1517/13543784.14.2.177. PMID 15757393.
8. Elancheran, R.; Maruthanila, V. L.; Ramanathan, M.; Kabilan, S.; Devi, R.; Kunnumakara, A.; Kotoky, Jibon (2015). "Recent discoveries and developments of androgen receptor based therapy for prostate cancer". MedChemComm. 6 (5): 746–768. doi:10.1039/C4MD00416G. ISSN 2040-2503.
9. Leonard, Matthew J.; Lingham, Anthony R.; Niere, Julie O.; Jackson, Neale R. C.; McKay, Peter G.; Hügel, Helmut M. (2014). "Alternative synthesis of the anti-baldness compound RU58841". RSC Adv. 4 (27): 14143–14148. doi:10.1039/C4RA00332B. ISSN 2046-2069.
10. Cousty-Berlin D, Bergaud B, Bruyant MC, Battmann T, Branche C, Philibert D (October 1994). "Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: relation of their systemic activity to the formation of a common metabolite". J. Steroid Biochem. Mol. Biol. 51 (1–2): 47–55. doi:10.1016/0960-0760(94)90114-7. PMID 7947350.

Further reading

• Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis CC, Blume-Peytavi U, Schäfer-Korting M (January 2005). "RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia". Pharmazie. 60 (1): 8–12. PMID 15700772.