X. Zhang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 439–443
443
inhibition of testosterone-enhanced tissue weights, with a
vehicle-treated control group set to 100% and a testoster-
one alone-treated control group set to 0%; (c) Agonist
assay: Test compound activity was determined as the
percent stimulation of tissue weight, with the vehicle-
treated control group set to zero percent and the testos-
terone alone-treated control group set to 100%; Synthesis
and SAR of novel hydantoin derivatives as selective
androgen receptor modulators: (d) Zhang, X.; Allan, G.
F.; Sbriscia, T.; Linton, O.; Lundeen, S. G.; Sui, Z. Bioorg.
Med. Chem. Lett. 2006, 16, 5763; The discovery of a
potent orally efficacious indole androgen receptor antag-
onist through in vivo screening: (e) Lanter, J. C.; Fiordel-
iso, J. J.; Jiang, W.; Allan, G. F.; Lai, M.-T.; Linton, O.;
Hahn, D.-W.; Lundeen, S. G.; Sui, Z. Bioorg. Med. Chem.
Acknowledgment
We thank Dr. Alexandra Shedlow and Dr. Derek Beau-
champ for coordination on obtaining the X-ray crystal-
lographic data.
Supplementary data
Supplementary data associated with this article can be
References and notes
7. Compound 10c was prepared from its enantiomeric pure
precursor of 6 obtained from Chiral Pak column separa-
tion. See the experimental section for spectroscopic data.
X-ray crystallography data for 10c (HCl salt) have been
deposited with Cambridge Crystallographic Data Centre
(CCDC). CCDC 623419 contains the supplementary
crystallographic data for this paper. These data can be
quest/cif, or by emailing data_request@ccdc.cam.ac.uk, or
by contacting The Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336033.
8. Varney, M. D.; Palmer, C. L.; Deal, J. G.; Webber, S.;
Welsh, K. M.; Bartlett, C. A.; Morse, C. A.; Smith, W.
W.; Janson, C. A. J. Med. Chem. 1995, 38, 1892.
9. Mature (150–200 g) castrated male Sprague–Dawley rats
were treated once daily for two weeks with test
compound in 20% cyclodextrin. The activity was deter-
mined following the same method with immature rat
agonist assay.
1. (a) Andres, N.-V. J. Clin. Endocrinol. Metab. 1999, 84,
3459; (b) Liu, P. Y.; Swerdloff, R. S.; Veldhuis, J. D.
J. Clin. Endocrinol. Metab. 2004, 89, 4789.
2. (a) Cosman, F.; Lindsay, R. Endocr. Rev. 1999, 20, 418;
(b) Katzenellenbogen, J. A.; O’Malley, B. W.; Katzenel-
lenbogen, B. S. Mol. Endocrinol. 1996, 10, 119; (c) Baracat,
E.; Haidar, M.; Lopez, F. J. J. Clin. Endocrinol. Metab.
1999, 84, 2020.
3. (a) Gao, W.; Bohl, C. E.; Dalton, J. T. Chem. Rev. 2005,
105, 3352; (b) Chen, J.; Kim, J.; Dalton, J. T. Mol.
Interventions 2005, 5, 173; (c) Basaria, S.; Wahlstrom, J.
T.; Dobs, A. S. J. Clin. Endocrinol. 2001, 86, 5108.
4. (a) Marhefka, C. A.; Gao, W.; Chung, K.; Kim, J.; He, Y.;
Yin, D.; Bohl, C.; Dalton, J. T.; Miller, D. D. J. Med.
Chem. 2004, 47, 993; (b) Hamann, L. G. Natl. Meet. Am.
Chem. Soc., Med. Chem. Div. 2004, 227, MEDI-175.
5. Zhang, X.; Li, X.; Sui, Z. PCT Int. Appl. WO 2006055184,
2006; Chem. Abstr. 2006, 495, 991.
6. (a) Hershberger, L. G.; Shipley, E. G.; Meyer, R. K. Proc.
Soc. Exp. Biol. Med. 1953, 83, 175; (b) Antagonist assay:
Test compound activity was determined as the percent
10. Mature (150–200 g) intact male rats were treated once
daily for six weeks with test compound.