1208 Journal of Medicinal Chemistry, 2009, Vol. 52, No. 4
Brief Articles
E. G.; Miller, M. A.; Nemeth, E. F.; Fox, J. Antagonizing the
parathyroid calcium receptor stimulates parathyroid hormone secretion
and bone formation in osteopenic rats. J. Clin. InVest. 2000, 105, 1595–
1604.
ing PTH release in a rapid and transient manner. Results from
further chemical and biological investigations of these active
series will be forthcoming.
(7) (a) Yang, W.; Wang, Y.; Roberge, J. Y.; Ma, Z.; Liu, Y.; Lawrence,
R. M.; Rotella, D. P.; Seethala, R.; Feyen, J. H. M.; Dickson, J. K.,
Jr. Discovery and structure-activity relationships of 2-benzylpyrro-
lidine-substituted aryloxypropanols as calcium-sensing receptor an-
tagonists. Bioorg. Med. Chem. Lett. 2005, 15, 1225–1228. (b)
Shcherbakova, I.; Balandrin, M. F.; Fox, J.; Ghatak, A.; Heaton, W. L.;
Conklin, R. L. 3H-Quinazolin-4-ones as a new calcilytic template for
the potential treatment of osteoporosis. Bioorg. Med. Chem. Lett. 2005,
15, 1557–1560. (c) Shcherbakova, I.; Huang, G.; Geoffroy, O. J.; Nair,
S. K.; Swierczek, K.; Balandrin, M. F.; Fox, J.; Heaton, W. L.; Conklin,
R. L. Design, new synthesis, and calcilytic activity of substituted 3H-
pyrimidin-4-ones. Bioorg. Med. Chem. Lett. 2005, 15, 2537–2540. (d)
Gavai, A. V.; Vaz, R. J.; Mikkilineni, A. B.; Roberge, J. Y.; Liu, Y.;
Lawrence, R. M.; Corte, J. R.; Yang, Wu; Bednarz, M.; Dickson, J. K.;
Ma, Z.; Seethala, R.; Feyen, J. H. M. Discovery of novel 1-arylm-
ethylpyrrolidin-2-ylethanolamines as calcium-sensing receptor antago-
nists. Bioorg. Med. Chem. Lett. 2005, 15, 5478–5482. (e) Kessler,
A.; Faure, H.; Petrel, C.; Rognan, D.; Cesario, M.; Ruat, M.; Dauban,
P.; Dodd, R. H. N1-Benzoyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-di-
aminocyclohexanes: development of 4-chlorophenylcarboxamide (Cal-
hex 231) as a new calcium sensing receptor ligand demonstrating
potent calcilytic activity. J. Med. Chem. 2006, 49, 5119–5128.
(8) Arey, B. J.; Seethala, R.; Ma, Z.; Fura, F.; Morin, J.; Swartz, J.; Vyas,
V.; Yang, W.; Dickson, J. K., Jr.; Feyen, J. H. M. A novel calcium-
sensing receptor antagonist transiently stimulates parathyroid hormone
secretion. In ViVo Endocrinol. 2005, 146, 2015.
Acknowledgment. We thank Dharmpal Dodd and Rogelio
Martinez for their original contributions to the preparation of
2-aminopyrimidine-5-carboxamides via solid-phase synthetic
chemistry routes.
Supporting Information Available: Detailed experimental
information on synthetic preparation and analytical data of 6a-t,
11a-o, and 18a-h. This material is available free of charge via
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