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The Crystal Structure of distrontium salt of 5-[bis(carboxymethyl)amino]-3-carboxymethyl-4-cyano-2-thiophenecarboxylic acid

Katarzyna Korczak 1Wojciech J. Szczepek 1Adam Andrzej Pietraszko 2Marek Kubiszewski 1Hanna M. Beczkowicz 1

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
2. Polish Academy of Sciences, Institute of Low Temperature and Structure Research (INTiBS), Okólna 2, Wrocław 50-422, Poland


Strontium ranelate, i.e. distrontium salt of 5-[bis(carboxymethyl)amino]-3-carboxymethyl-4-cyano-2-thiophenecarboxylic acid is licensed for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures. It reduces the risk of vertebral and non-vertebral fractures compared with placebo but has not been directly compared with other osteoporosis treatments [1].

Its crystal structure has been determined from X-ray diffraction data at 150K (using the single crystal diffractometer with CCD area detector). Very small (0.01*0.02*0.28mm) single crystals of strontium ranelate octahydrate have been obtained according to the procedure described in Example 1d (second method) disclosed in EP 415 850 B1 [2]. The crystal structure was solved by direct method [SHELXL 97] and was refined by full matrix least squares. The experimental crystallographic data are following:
Space group: triclinic, P-1(2), with the lattice parameters at 150K:
a = 8.2580(17) Ǻ, b = 11.5140(23) Ǻ, c = 12.4270(25) Ǻ
α = 111.95(3) º, β = 102.62(3) º, γ = 91.27(3) º
The projection of ranelic acid anion with the coordination polyhedron of Sr ions and the packing of the molecule in the crystal lattice along b axis are illustrated in the bottom figures.

The distances and angles in the strontium ranelate molecule are comparable to those found in the tetraethyl ester of ranelic acid [3]. The crystal structure contains 8 molecules of water. The symmetry independent Sr(1) and Sr(2) ions are complexed to oxygen 7 and 9, respectively, coming from carboxylate oxygens and the water molecules. The polyhedrons of Sr ions form the layers in the (01–1) plane. The water molecules occupying the positions between layers are strongly disordered [4].

[1] New drug evaluation, “Strontium Ranelate”, 2005, May.
[2] EP 415 850 B1 = US 5,128,367.
[3] Hong-Tao W., Min J., Acta Cryst. Sect. E, 2007, 63, 1341.
[4] Dan M., Cheetham A.K., Rao C.N.R., Inorg. Chem., 2006, 45, 8227.


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Submitted: 2008-03-17 20:26
Revised:   2009-06-07 00:48