Ольпадроновая кислота

Description

Olpadronic acid is a nitrogen-containing bisphosphonate, 3-(dimethylamino)-1-hydroxypropylidene-1,1-bisphosphonic acid. Structural type “geminal bisphosphonate”: two phosphonate residues at one carbon atom, there is also a hydroxyl group, the side chain ends with a dimethylamino group. The combination of P-C-P and hydroxyl gives a high affinity for the bone mineral phase, and the tertiary nitrogen is responsible for inhibiting a key enzyme in the mevalonate pathway.

Basic Attributes

• CAS No.: 63132-39-8
• Chemical formula: C5H15NO7P2
• Molecular Weight: 263.121
• Exact weight: 263.12
• UNII: 874HHB2V3S
• DSSTox ID: DTXSID50212479
• HS Code: 2931900090

Physico-chemical characteristics

• PSA: 139
• XLogP3: −5.9
• Density: 1.706 g/cm³
• Boiling point: 590.1 °C at 760 mm Hg. Art.
• Flash point: 310.7 °C
• Refractive index: 1.566

The XLogP3 value of −5.9 is one of the lowest among substances in this group. The molecule is extremely hydrophilic and is practically not distributed in lipid phases, which is typical for bisphosphonates and determines their low bioavailability when taken orally and accumulation in bone tissue.

Mechanism of action

The target is farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway. Nitrogen-containing bisphosphonates block it and thereby stop the formation of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. Without these isoprenoids, small GTPases do not undergo prenylation, lose their correct localization in the cell, and cannot transmit signals. In the osteoclast, this disrupts the organization of the cytoskeleton and the corrugated border - bone resorption stops.

Applications

• substance of antiresorptive drugs
• accompanying therapy in oncology: correction of hypercalcemia in malignant neoplasms
• reduction in the incidence of fractures and pain in metastatic bone lesions
• starting compound for the preparation of bisphosphonic acid derivatives for anti-osteoporosis agents

Safety Information

• Hazard Statements: H315 - Causes skin irritation
• GHS classification, signal word "Warning": H315 (100%), class "skin corrosion and irritation"
• Precautions: P261, P264, P271, P280, P302 + P352, P304 + P340, P305 + P351 + P338, P312, P321, P332 + P313, P337 + P313, P362, P403 + P233, P405, P501
• Basis of classification: information from 1 company based on 1 notification to the ECHA C and L register

Storage and handling

Tightly closed container, dry place, ventilation (P403 + P233), locked up (P405). When working, wear gloves and protective clothing, eye protection, and avoid inhaling dust. In case of contact with skin, remove contaminated clothing and wash with soap and water; If irritated, seek medical attention. Hand over waste and containers to a licensed operator.