Neridronic acid

Base Information

• Chemical Name: Neridronic acid
• CAS No.: 79778-41-9
• Molecular Formula: C6H17NO7P2
• Molecular Weight: 277.151
• European Community (EC) Number: 635-979-9
• UNII: 8U27U3RIN4
• DSSTox Substance ID: DTXSID40868545
• Nikkaji Number: J553.014H
• Wikipedia: Neridronic_acid
• Wikidata: Q1651770
• NCI Thesaurus Code: C66230
• Pharos Ligand ID: BL47WR9F82UL
• Metabolomics Workbench ID: 152750
• ChEMBL ID: CHEMBL55214
• Mol file: 79778-41-9.mol

Synonyms:6-AHHDP;6-amino-1-hydroxyhexane-1,1-diphosphonate;6-amino-1-hydroxyhexylidene-1,1-bisphosphonic acid;AHHexBP;aminohexane bisphosphonate;neridronate;neridronic acid

Chemical Property of Neridronic acid

Chemical Property:

• Appearance/Colour: white solid
• Vapor Pressure: 6.66E-17mmHg at 25°C
• Melting Point: 245°
• Refractive Index: 1.569
• Boiling Point: 600.1 °C at 760 mmHg
• PKA: 1.93±0.10(Predicted)
• Flash Point: 316.7 °C
• PSA: 180.93000
• Density: 1.658 g/cm³
• LogP: 0.20730
• Storage Temp.: 2-8°C
• Solubility.: H2O: 8 mg/mL, soluble
• XLogP3: -5.8
• Hydrogen Bond Donor Count: 6
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 7
• Exact Mass: 277.04802588
• Heavy Atom Count: 16
• Complexity: 286

Purity/Quality:

98%,99%, ^*data from raw suppliers

Neridronate ≥97% (NMR), solid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: C(CCC(O)(P(=O)(O)O)P(=O)(O)O)CCN
• Recent ClinicalTrials: Efficacy and Safety of Intravenous Neridronic Acid in CRPS
• Recent EU Clinical Trials: Randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of treatment with Neridronate 100 mg (4 infusions over a period of 10 days) in patients with transient osteoporosis of the hip.
• Description: Neridronic acid was launched in Italy as intravenous or intramuscular injection for the treatment of osteogenesis imperfecta. It is the first drug launched worldwide for this “orphan disease” characterized by a fragility of the bone. Sufferers risk frequent fractures commencing during infancy, eventually leading to bone deformation and a severe deterioration of the quality of life and life expectancy. Neridronic acid is structurally related to the second generation of bisphosphonates characterized by an amino terminal group and can be synthesized by treating E-aminocaproic acid with phosphoric acid and phosphorous trichloride. Bisphosphonates, synthetic analogs of the endogenous mineral deposition inhibitor pyrophosphate, are extremely potent inhibitors of bone resorption and increase bone mineral density, possibly by inhibiting the activity of osteoclasts and promoting the death of these bone-eroding cells. In vitro, neridronic acid was a poor inhibitor of phagocytosis, but significantly and dose dependently inhibited 8glucuronidase release and superoxide anion production in the rat peritoneal macrophage, two parameters that may have a part in bone resorption. In a clinical study on patients with osteogenesis imperfecta, neridronic acid increased remarkably bone mass in young growing individuals. In adults the changes were less important but still significant. Neridronic acid is an amino bisphosphonate that inhibits farnesyl pyrophosphate (FPP) synthase (IC50 = 388.2 nM in a cell-free assay). It decreases the differentiation of RAW 264.7 cells into osteoclasts in a CRL-12257 co-culture model of osteoclastogenesis when used at concentrations ranging from 0.001 to 100 μM. Neridronic acid (30 μM) inhibits FGF2-induced proliferation and tube formation in human umbilical vein endothelial cells (HUVECs). It reduces the loss of trabeculae and increases bone density in the tibial metaphysis of growing rats when administered subcutaneously at a dose of 0.1 mg/kg per day.

Technology Process of Neridronic acid

There total 6 articles about Neridronic acid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 89.0%

6-aminohexanoic acid (60-32-2,93208-38-9) → neridronate (79778-41-9)

Guidance literature:

6-aminohexanoic acid; With phosphorus trichloride; In methanesulfonic acid; at 80 - 85 ℃;

With water; In methanesulfonic acid; at 105 ℃; for 4h;

DOI:10.3390/molecules25010229

Reference yield: 89.0%

[6-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-hydroxy-1-phosphonohexyl]phosphonic acid (948317-80-4) → neridronate (79778-41-9)

Guidance literature:

With hydrazine hydrate; In water; at 20 ℃; for 0.5h;

DOI:10.1002/ejoc.200601067

Reference yield:

phosphorous acid (10294-56-1) + 6-aminohexanoic acid (60-32-2,93208-38-9) → neridronate (79778-41-9)

Guidance literature:

With anhydrous phosphorus trichloride;

upstream raw materials:

6-aminohexanoic acid

[6-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-hydroxy-1-phosphonohexyl]phosphonic acid

6-phthalimidohexanoic acid

6-phthalimidohexanoyl chloride

Refernces

• 1、 -. "AMIDE-LINKED EP4 AGONIST-BISPHOSPHONATE COMPOUNDS AND USES THEREOF". Paragraph 00140-00141. . Retrieved 2017/01/31.
• 2、 Alanne, Aino-Liisa,Ylisirnioe, Markku,Turhanen, Petri,Peraeniemi, Sirpa,Vepsaelaeinen, Jouko,Hyvoenen, Helena,Lahtinen, Manu,Kolehmainen, Erkki. "Systematic study of the physicochemical properties of a homologous series of aminobisphosphonates". . p. 10928 - 10945,18. Retrieved 2020/09/09.