753449-67-1

Name	Ronacaleret
CAS	753449-67-1
EINECS(EC#)	815-090-4
Molecular Formula	C25H31F2NO4
Molecular Weight	447.51
MOL File	753449-67-1.mol

Synonyms

Ronacaleret FQJISUPNMFRIFZ-HXUWFJFHSA-N Benzenepropanoic acid, 3-[(2R)-3-[[2-(2,3-dihydro-1H-inden-2-yl)-1,1-diMethylethyl]aMino]-2-hydroxypropoxy]-4,5-difluoro-

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Chemical Properties

Boiling point	624.4±55.0 °C(Predicted)
density	1.222±0.06 g/cm3(Predicted)
pka	4.54±0.10(Predicted)

Hazard Information

Uses

Ronacaleret (SB 751689) is an orally active, potent, and selective calcium-sensing receptor (CaSR) antagonist that stimulates endogenous parathyroid hormone release from the parathyroid glands. Ronacaleret (SB 751689) is used for the study of postmenopausal osteoporosis[1].

in vivo

Ronacaleret (SB 751689, 3 mg/kg/day) preserves klotho expression and renal function with the reductions in serum phosphate and albuminuria in 5/6-nephrectomized rats^[3].

Animal Model:	7-week-old Wistar rats^[2].
Dosage:	3 mg/kg/day (dissolved in 10% β-cyclodextrin solution).
Administration:	Administered by an osmotic pump that was implanted subcutaneously.
Result:	Increased renal expression of klotho in a dose-dependent manner. Decreased serum phosphate and FGF23 with the increased fractional excretion of phosphate without changes in serum calcium. Appeared to similarly protect podocytes. Reduced FGF23 and because FGF23 enhanced klotho expression.

References

[1] Gy?rgy Szabó, et al. Discovery of dihydropyrazino-benzimidazole derivatives as metabotropic glutamate receptor-2 (mGluR2) positive allosteric modulators (PAMs). Eur J Med Chem. 2020 Jan 15:186:111881. DOI:10.1016/j.ejmech.2019.111881
[2] Tsuneo Takenaka , et al. Antialbuminuric actions of calcilytics in the remnant kidney. Am J Physiol Renal Physiol. 2015 Aug 1;309(3):F216-26. DOI:10.1152/ajprenal.00003.2015
[3] Marta Johnson, et al. Inhibition of Intestinal OATP2B1 by the Calcium Receptor Antagonist Ronacaleret Results in a Significant Drug-Drug Interaction by Causing a 2-Fold Decrease in Exposure of Rosuvastatin. Drug Metab Dispos. 2017 Jan;45(1):27-34. DOI:10.1124/dmd.116.072397

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