N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation.

Article Details

Citation

Copy to clipboard

Nirschl AA, Zou Y, Krystek SR Jr, Sutton JC, Simpkins LM, Lupisella JA, Kuhns JE, Seethala R, Golla R, Sleph PG, Beehler BC, Grover GJ, Egan D, Fura A, Vyas VP, Li YX, Sack JS, Kish KF, An Y, Bryson JA, Gougoutas JZ, DiMarco J, Zahler R, Ostrowski J, Hamann LG

N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation.

J Med Chem. 2009 May 14;52(9):2794-8. doi: 10.1021/jm801583j.

PubMed ID

19351168 [ View in PubMed

]

Abstract

A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-chloro-4-{[(1R,3Z,7S,7aS)-7-hydroxy-1-(trifluoromethyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-ylidene]amino}-3-methylbenzonitrile	Androgen receptor	Ki (nM)	0.3	7.6	22	Details
2-chloro-4-{[(1R,3Z,7S,7aS)-7-hydroxy-1-(trifluoromethyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-ylidene]amino}-3-methylbenzonitrile	Androgen receptor	EC 50 (nM)	0.2	7.6	22	Details
BMS-564929	Androgen receptor	Ki (nM)	14	7.6	22	Details
BMS-564929	Androgen receptor	EC 50 (nM)	7.8	7.6	22	Details