RD-162

RD-162

Clinical data
Routes of administration	By mouth
Drug class	Nonsteroidal antiandrogen
Identifiers
IUPAC name 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	915087-27-3^Y
PubChem CID	11957756
ChemSpider	10132004
UNII	5ZE6THH5VF
ChEMBL	ChEMBL1082410
CompTox Dashboard (EPA)	DTXSID301337376
Chemical and physical data
Formula	C22H16F4N4O2S
Molar mass	476.45 g·mol^−1
3D model (JSmol)	Interactive image
SMILES 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 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 a second-generation nonsteroidal antiandrogen (NSAA) which was developed for the treatment of prostate cancer but was never marketed.^[1] It acts as a potent and selective silent antagonist of the androgen receptor (AR).^[1] The drug is a diarylthiohydantoin derivative.^[1] It is closely related to enzalutamide and apalutamide.^[1] Both RD-162 and enzalutamide show 5- to 8-fold higher affinity for the AR than the first-generation NSAA bicalutamide, and only 2- to 3-fold lower affinity than dihydrotestosterone (DHT), the major endogenous ligand of the receptor in the prostate gland.^[1]

RD-162 and enzalutamide were developed together and were derived from the nonsteroidal androgen RU-59063, which itself was derived from the first-generation NSAA nilutamide.^[2] RD-162 and enzalutamide were selected as the lead compounds from a group of over 200 compounds that were synthesized and assayed for antiandrogenic activity.^[1] Enzalutamide was ultimately selected from the two for further clinical 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 (a carbon atom in one of the phenyl rings of RD-162 swapped with a nitrogen atom in apalutamide). Apalutamide was approved for the treatment of prostate cancer in 2018.^[3]

References

1. Tran 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".