About this Biochemistry, Genetics and Molecular Biology article

N2-Benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor by Albane Kessler; Hélène Faure; Christophe Petrel; Martial Ruat; Philippe Dauban; Robert H. Dodd is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

The synthesis and calcimimetic activities of two new families of compounds are described. The most active derivatives of the first family, and 4d, respectively, tested at 10 lM) produced 98 ± 6% and 95 ± 4%, respectively, of the maximal stimulation of [ 3 H]inositol phosphates production obtained by 10 mM Ca 2þ in CHO cells expressing the rat calcium sensing receptor (CaSR). The second family of calcimimetics was obtained by conformationally restraining the compounds of type 4 to provide the 2-aminomethyl derivatives 5. One of these compounds, (R)-2-[N-(1-(1-naphthyl)ethyl)aminomethyl]indole ((R)-5a, calindol), displayed improved calcimimetic activity compared to 4b and 4d as well as stereoselectivity. In the presence of 2 mM Ca 2þ , calindol stimulated [ 3 H]inositol phosphates accumulation with an EC 50 of 1.0 ± 0.1 or 0.31 ± 0.05 lM in cells expressing the rat or the human CaSR, respectively. The calcimimetic activities of these novel compounds were shown to be due to a specific interaction with the CaSR.

Author

Albane Kessler; Hélène Faure; Christophe Petrel; Martial Ruat; Philippe Dauban; Robert H. Dodd

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0960-894X)

Published

2004

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)