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RD-162

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
RD-162
Clinical data
Routes of
administration
By mouth
Drug classNonsteroidal antiandrogen
Identifiers
  • 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
CAS Number
PubChemCID
ChemSpider
UNII
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC22H16F4N4O2S
Molar mass476.45 g·mol−1
3D model (JSmol)
  • CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(C=C4)C#N)C(F)(F)F)F
  • InChI=1S/C22H16F4N4O2S/c1-28-18(31)15-6-5-14(10-17(15)23)30-20(33)29(19(32)21(30)7-2-8-21)13-4-3-12(11-27)16(9-13)22(24,25)26/h3-6,9-10H,2,7-8H2,1H3,(H,28,31)
  • Key:JPQFGMYHKSKKGW-UHFFFAOYSA-N

RD-162 is asecond-generationnonsteroidal antiandrogen (NSAA) which was developed for the treatment ofprostate cancer but was never marketed.[1] It acts as apotent andselectivesilent antagonist of theandrogen receptor (AR).[1] The drug is a diarylthiohydantoinderivative.[1] It is closely related toenzalutamide andapalutamide.[1] Both RD-162 and enzalutamide show 5- to 8-fold higheraffinity for the AR than the first-generation NSAAbicalutamide, and only 2- to 3-fold lower affinity thandihydrotestosterone (DHT), the majorendogenousligand of the receptor in theprostate gland.[1]

RD-162 and enzalutamide were developed together and were derived from thenonsteroidal androgenRU-59063, which itself was derived from thefirst-generation NSAAnilutamide.[2] RD-162 and enzalutamide were selected as thelead compounds from a group of over 200 compounds that weresynthesized andassayed forantiandrogenic activity.[1] Enzalutamide was ultimately selected from the two for furtherclinical development and was eventually marketed.[1] RD-162 is also very closely related to apalutamide, with the two compounds differing only by the replacement of a single atom (acarbon atom in one of thephenyl rings of RD-162 swapped with anitrogen atom in apalutamide). Apalutamide was approved for the treatment of prostate cancer in 2018.[3]

References

[edit]
  1. ^abcdefgTran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (2009)."Development of a second-generation antiandrogen for treatment of advanced prostate cancer".Science.324 (5928):787–90.Bibcode:2009Sci...324..787T.doi:10.1126/science.1168175.PMC 2981508.PMID 19359544.
  2. ^Liu B, Su L, Geng J, Liu J, Zhao G (2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor".ChemMedChem.5 (10):1651–61.doi:10.1002/cmdc.201000259.PMID 20853390.S2CID 23228778.
  3. ^"Apalutamide - Janssen Research and Development - AdisInsight".


ARTooltip Androgen receptor
Agonists
SARMsTooltip Selective androgen receptor modulator
Antagonists
GPRC6A
Agonists


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