229. Alendronic Acid

Nomenclature

CAS number: 66376-36-1
P,P′-(4-Amino-1-hydroxybutylidene)bisphosphonic acid; α-hydroxy-δ-aminobutylidenediphosphonic acid; 4-amino-1-hydroxybutane-1,1-diphosphonic acid; ABDP.
C4H13NO7P2; mol wt 249.10.
C 19.29%, H 5.26%, N 5.62%, O 44.96%, P 24.87%.

Description and references

Bisphosphonate antiresorptive agent. Prepn: M. I. Kabachnik et al., Bull. Acad. Sci. USSR, 27, 374 (1978). See also: BE 903519; G. Staibano, US 4705651 (1986, 1987 both to Gentili). Improved prepn: G. R. Kieczykowski et al., J. Org. Chem. 60, 8310 (1995). Pharmacokinetics: J. H. Lin et al., Drug Metab. Dispos. 19, 926 (1991). Mechanism of action: M. Sato et al., J. Clin. Invest. 88, 2095 (1991). Determn by HPLC in urine: W. F. Kline et al., J. Chromatogr. 534, 139 (1990); by IC in pharmaceutical formulations: E. W. Tsai et al., ibid. 596, 217 (1992). Clinical evaluation in malignant hypercalcaemia: R. Rizzoli et al., Int. J. Cancer 50, 706 (1992). Clinical trial in postmenopausal osteoporosis: U. A. Liberman et al., N. Engl. J. Med. 333, 1437 (1995); in prevention of bone loss in women: D. Hosking et al., ibid. 338, 485 (1998). Review of clinical experience on bone mineral density in men: A. M. Sawka et al., J. Clin. Densitom. 8, 7-13 (2005); of long-term treatment: M. C. Hochberg, R. Rizzoli, Expert Opin. Pharmacother. 7, 1201-1210 (2006).

Chemical structure

Properties

Fine white powder, mp 233-235° (dec). pK1 2.72 ±0.05; pK2 8.73 ±0.05; pK3 10.5 ±0.1; pK4 11.6 ±0.1 at 25°, (0.1M KCl).

Derivative

Monosodium salt trihydrate.

Nomenclature

CAS number: 121268-17-5
Alendronate sodium; MK-217; G-704650; Adronat (Neopharmed); Alendros (Abiogen); Bonalon (Merck & Co.); Dronal (Sigma-Tau); Fosamac (Merck & Co.); Fosamax (Merck & Co.); Onclast (Merck & Co.).
C4H12NNaO7P2.3H2O; mol wt 325.12.
C 14.78%, H 5.58%, N 4.31%, Na 7.07%, O 49.21%, P 19.05%.

Properties

White, crystalline, nonhygroscopic powder, mp 257-262.5°. Sol in water; very slightly sol in alcohol. Practically insol in chloroform.

Therapeutic Category

Bone resorption inhibitor.

Keywords

Antiosteoporotic; Antipagetic; Bone Resorption Inhibitor