RU-58841
Clinical data
Other namesPSK-3841; HMR-3841
Drug classNonsteroidal antiandrogen
Identifiers
  • 4-[3-(4-Hydroxybutyl)-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl]-2-(trifluoromethyl)benzonitrile
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H18F3N3O3
Molar mass369.344 g·mol−1
3D model (JSmol)
  • CC1(C(=O)N(C(=O)N1CCCCO)C2=CC(=C(C=C2)C#N)C(F)(F)F)C
  • 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, also known as PSK-3841 or HMR-3841, is a nonsteroidal antiandrogen (NSAA) which was initially developed in the 1980s by Roussel Uclaf, the French pharmaceutical company from which it received its name. 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][1] The compound is similar in structure to the NSAA RU-58642 but contains a different side-chain.[4] These compounds are similar in chemical structure to nilutamide,[5] which is related to flutamide, bicalutamide, and enzalutamide, all of which are NSAAs similarly.[6] RU-58841 can be synthesized either by building the hydantoin moiety or by aryl coupling to 5,5-dimethylhydantoin.[7]

RU-58841 produces cyanonilutamide (RU-56279) and RU-59416 as metabolites in animals.[8] Cyanonilutamide has relatively low affinity for the androgen receptor but shows significant antiandrogenic activity in animals.[8] RU-59416 has very low affinity for the androgen receptor.[8]

See also

References

  1. ^ a b Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, et al. (January 2005). "RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia". Die Pharmazie. 60 (1): 8–12. PMID 15700772.
  2. ^ "PSK-3841 (HMR-3841, RU-58841)". AdisInsight. Springer Nature Switzerland AG.
  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". The Journal of Steroid Biochemistry and Molecular Biology. 48 (1): 55–60. doi:10.1016/0960-0760(94)90250-X. PMID 8136306. S2CID 31052540.
  4. ^ Van Dort ME, Jung YW (April 2001). "Synthesis and structure-activity studies of side-chain derivatized arylhydantoins for investigation as androgen receptor radioligands". Bioorganic & Medicinal Chemistry Letters. 11 (8): 1045–1047. doi:10.1016/s0960-894x(01)00146-9. PMID 11327585.
  5. ^ Poulos GA, Mirmirani P (February 2005). "Investigational medications in the treatment of alopecia". Expert Opinion on Investigational Drugs. 14 (2): 177–184. doi:10.1517/13543784.14.2.177. PMID 15757393. S2CID 24694921.
  6. ^ Elancheran R, Maruthanila VL, Ramanathan M, Kabilan S, Devi R, Kunnumakara A, Kotoky J (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. S2CID 72654573.
  7. ^ Leonard MJ, Lingham AR, Niere JO, Jackson NR, McKay PG, Hügel HM (2014). "Alternative synthesis of the anti-baldness compound RU58841". RSC Adv. 4 (27): 14143–14148. Bibcode:2014RSCAd...414143L. doi:10.1039/C4RA00332B. ISSN 2046-2069.
  8. ^ a b c 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". The Journal of Steroid Biochemistry and Molecular Biology. 51 (1–2): 47–55. doi:10.1016/0960-0760(94)90114-7. PMID 7947350. S2CID 29752252.

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