5N-Bicalutamide

5N-Bicalutamide

Clinical data
Other names	5-Azabicalutamide
Drug class	Nonsteroidal antiandrogen
ATC code	None
Identifiers
IUPAC name N-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methylpropanamide
PubChem CID	118614933
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C17H13F4N3O4S
Molar mass	431.362 g/mol g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CS(=O)(=O)C1=CC=C(C=C1)F)(C(=O)NC2=CN=C(C(=C2)C(F)(F)F)C#N)O
InChI InChI=1S/C17H13F4N3O4S/c1-16(26,9-29(27,28)12-4-2-10(18)3-5-12)15(25)24-11-6-13(17(19,20)21)14(7-22)23-8-11/h2-6,8,26H,9H2,1H3,(H,24,25) Key:JWQMHMGGGRQTSY-UHFFFAOYSA-N

5N-Bicalutamide, or 5-azabicalutamide, is a highly potent nonsteroidal antiandrogen (NSAA) which was discovered in 2016. It is a structural modification of bicalutamide differing it from it only by the replacement of a carbon atom with a nitrogen atom in one of its phenyl rings. Similarly to bicalutamide, the drug acts as a selective antagonist of the androgen receptor (AR). However, unlike bicalutamide, it is a reversible covalent antagonist and stays bound to the receptor for a far longer amount of time. As a result of this difference, 5N-bicalutamide has markedly improved potency relative to bicalutamide, with approximately 150-fold higher affinity for the AR (K_i = 0.15 nM versus 22.3 nM) and about 20-fold greater functional inhibition (IC₅₀ = 15 nM versus 310 nM) of the AR. Future studies of 5N-bicalutamide in normal and mutated prostate cancer cells are planned or underway and it is anticipated that N-bicalutamide may be able to overcome resistance to current antiandrogens that are used in the treatment of prostate cancer.

Enzalutamide and related second-generation NSAAs like RD-162 and apalutamide were derived from bicalutamide and as a result are similar to it in chemical structure. They have up to about 10-fold higher affinity for the AR than does bicalutamide and hence are comparatively more potent and efficacious antiandrogens. However, their structures are rigidified such that the analogous structural modification that was done with bicalutamide to create 5N-bicalutamide could not be used to increase affinity or potency with them. Enzalutamide was described in 2013 as "the emperor of all antiandrogens" and other second-generation NSAAs have similar potency to it, so 5N-bicalutamide would appear to be the most potent AR antagonist to have been developed thus far.

See also

• Cyanonilutamide
• N-Terminal domain antiandrogen

References

Latest research - 5N-Bicalutamide

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