Zoledronic acid Chemical Properties

Melting point:

193-2040C (dec)

Boiling point:

764.0±70.0 °C(Predicted)

Density 

2.13±0.1 g/cm3(Predicted)

pka

1.41±0.10(Predicted)

CAS DataBase Reference

118072-93-8(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

21/22-36/37/38

Safety Statements 

24/25-36/37/39

HS Code 

2933399090

Zoledronic acid Usage And Synthesis

Description

Zoledronic acid is a white, crystalline powder that is available in vials for reconstitution for IV infusion over at least 15 minutes. It does not undergo metabolic transformation and does not inhibit CYP450 enzymes. Clearance of this agent is dependent on the patient's creatinine clearance, not on dose. Serum creatinine levels should be evaluated before every treatment. Zolendronic acid is contraindicated in patients with severe renal impairment.

Chemical Properties

White Solid

Originator

Zometa,Novartis Pharma,Switz

Uses

Bisphosphonate antiresorptive agent

Uses

bone resorption inhibitor

Definition

ChEBI: An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.

Manufacturing Process

With stirring and under reflux, 8.6 g (0.053 mole) of imidazol-4-yl acetic acid hydrochloride, 7.1 ml of 85% phosphoric acid and 25 ml of chlorobenzene are heated to 100°C. Then 13.9 ml of phosphorus trichloride are added dropwise at 100°C, whereupon evolution of gas occurs. Over the course of 30 min a dense mass precipitates from the reaction mixture. The batch is heated for 3 hours to 100°C and the supernatant chlorobenzene is removed by decantation. With stirring and under reflux, the residual viscous mass is heated to the boil for 3 hours with 40 ml of 9 N hydrochloric acid. The batch is filtered hot with the addition of carbon and the filtrate is diluted with acetone, whereupon the crude 2-(imidazol-4-yl)-1-hydroxy-ethane-1,1- diphosphonic acid precipitates. This product is recrystallised from water. Melting point: 238-240°C (dec.).

brand name

Zometa (Novartis).

Therapeutic Function

Bone calcium regulator

Biological Functions

Zoledronic acid, a bisphosphonate, was approved by the U.S. FDA in 2001 for the treatment of hypercalcemia of malignancy, a metabolic complication that can be life-threatening. Hypercalcemia of malignancy can occur in up to 50% of patients diagnosed with advanced breast cancer, multiple myeloma, and nonsmall cell lung cancer. This condition arises when chemical moieties produced by the tumor cause overstimulation of osteoclasts. When there is an increase in bone degradation, there is a concomitant release of calcium into the plasma. When serum concentrations of calcium rapidly elevate, the kidneys are unable to handle the overload, and hypercalcemia results. This can lead to dehydration, nausea, vomiting, fatigue, and confusion. Zoledronic acid effectively decreases plasma calcium concentrations via inhibition of bone resorption (inhibition of osteoclastic activity and induction of osteoclast apoptosis). It also prevents the increase in osteoclastic activity caused by tumor-based stimulatory factors. Additionally zoledronic acid has been approved by the U.S. FDA for the treatment of multiple myeloma and bone metastases associated with solid tumor–based cancers (e.g., prostrate and lung). This agent is currently in late-stage clinical trials for the treatment and prevention of osteoporosis and, if approved, will be formulated as a 5-mg, once-yearly IV infusion.

Clinical Use

Zoledronic acid is most commonly given to patients whose cancer is no longer responding to hormones, but it also may be given to prevent the bone thinning and weakening that results from hormonal treatments.

Zoledronic acid(118072-93-8)Related Product Information

• Rocuronium bromide
• ZOLEDRONIC ACID-D3
• 2-(1H-imidazol-1-yl)acetic acid hydrochloride (intermediate of zoledronic acid)
• Zoledronic Acid-d2Discontinued: Z623502
• zoledronic acid hydrate,ZOLEDRONIC ACID MONOHYDRATE
• ACETIC ACID, 2-(1H-IMIDAZOL-1-YL) HYDROCHLORIDE(INTERMEDIATES OF ZOLEDRONIC ACID)
• Citric acid
• Imidazole
• CHLOROPHOSPHONAZO III
• Hyaluronic acid
• 1-Hydroxyethylidene-1,1-diphosphonic acid
• ZOLEDRONIC ACID-15N2,13C2
• ZOLEDRONIC ACID, DISODIUM SALT, TETRAHYDRATE
• Zoledronic acid
• Stearic acid
• Ethyl 2-(Chlorosulfonyl)acetate
• Folic acid
• Ascoric Acid