New aminopropandiol derivatives as orally available and short-acting calcium-sensing receptor antagonists

Yuko Shinagawa; Teruhiko Inoue; Kazuyuki Hirata; Takeo Katsushima; Takashi Nakagawa; Yushi Matsuo; Masanori Shindo; Hiromasa Hashimoto

doi:10.1016/j.bmcl.2010.04.035

New aminopropandiol derivatives as orally available and short-acting calcium-sensing receptor antagonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3809-13. doi: 10.1016/j.bmcl.2010.04.035. Epub 2010 Apr 14.

Authors

Yuko Shinagawa¹, Teruhiko Inoue, Kazuyuki Hirata, Takeo Katsushima, Takashi Nakagawa, Yushi Matsuo, Masanori Shindo, Hiromasa Hashimoto

Affiliation

¹ Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, Japan. [email protected]

PMID: 20472433
DOI: 10.1016/j.bmcl.2010.04.035

Abstract

Synthesis and structure-activity relationship studies on a new aminopropandiol class of derivatives as calcium-sensing receptor antagonists are described. Modification of the phenolic moiety of a calcilytic compound NPS 2143 led to the identification of an orally available compound (R,R)-31 which demonstrated a rapid and transient stimulation of PTH release in rats.

MeSH terms

Animals
Biological Availability
Osteoporosis / drug therapy
Parathyroid Hormone / metabolism
Propanolamines / chemistry*
Propanolamines / pharmacology
Propanolamines / therapeutic use
Rats
Receptors, Calcium-Sensing / antagonists & inhibitors
Structure-Activity Relationship

Substances

Parathyroid Hormone
Propanolamines
Receptors, Calcium-Sensing