10187. Zoledronic Acid

Nomenclature

CAS number: 118072-93-8
P,P′-[1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic acid; 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid.
C5H10N2O7P2; mol wt 272.09.
C 22.07%, H 3.70%, N 10.30%, O 41.16%, P 22.77%.

Description and references

Bisphosphonate antiresorptive agent. Prepn: JP Kokai 88 150291; K. A. Jaeggi, L. Wilder, US 4939130 (1988, 1990 both to Ciba-Geigy). Effect on bone metabolism: J. R. Green et al., J. Bone Miner. Res. 9, 745 (1994). Determn in plasma by enzyme inhibition assay: F. Risser et al., J. Pharm. Biomed. Anal. 15, 1877 (1997). Stability-indicating HPLC method: B. Mallikarjuna Rao et al., J. Pharm. Biomed. Anal. 39, 781 (2005). Series of articles on pharmacology and clinical development: Br. J. Clin. Pract. Suppl. 87, 15-22 (1996). Review of clinical experience in metastatic bone disease: D. Santini et al., Expert Opin. Biol. Ther. 6, 1333-1348 (2006); in Paget's disease: G. M. Keating, L. J. Scott, Drugs 67, 793-804 (2007). Clinical trial of once-yearly treatment of osteoporosis: D. M. Black et al., N. Engl. J. Med. 356, 1809 (2007).

Chemical structure

Derivative

Monohydrate.

Nomenclature

CAS number: 165800-06-6
CGP-42446; Aclasta (Novartis); Reclast (Novartis); Zometa (Novartis).
C5H10N2O7P2.H2O; mol wt 290.10.
C 20.70%, H 4.17%, N 9.66%, O 44.12%, P 21.35%.

Properties

White crystalline powder from water, mp 239° (dec). Highly sol in 0.1N NaOH; sparingly sol in water, 0.1N HCl. Practically insol in organic solvents. pH of 0.7% aq soln is approx 2.0.

Derivative

Disodium salt tetrahydrate.

Nomenclature

CAS number: 165800-07-7
Zoledronate disodium; CGP-42446A.
C5H8N2Na2O7P2.4H2O; mol wt 388.11.
C 15.47%, H 4.16%, N 7.22%, Na 11.85%, O 45.35%, P 15.96%.

Derivative

Trisodium salt hydrate.

Nomenclature

CAS number: 165800-08-8
Zoledronate trisodium; CGP-42446B.
(C5H7N2Na3O7P2)5.2H2O; mol wt 1726.21.
C 17.39%, H 2.28%, N 8.11%, Na 19.98%, O 34.29%, P 17.94%.

Therapeutic Category

Bone resorption inhibitor.

Keywords

Antiosteoporotic; Antipagetic; Bone Resorption Inhibitor