Basic information
- Standard SMILES
O=P(O)(O)C(Sc1ccc(Cl)cc1)P(=O)(O)O- InChIKey
DKJJVAGXPKPDRL-UHFFFAOYSA-N- Molecular formula
- C7H9ClO6P2S
- Average molar mass
- 318.61 g/mol
- Monoisotopic mass
- 317.92835995
Overview
Tiludronic acid is an organochlorine compound.
Names & identifiers
- Preferred name
- Tiludronic Acid
- IUPAC
- [(4-chlorophenyl)sulfanyl-phosphonomethyl]phosphonic acid
- English name
- Tiludronic acid
- Molecular formula
- C7H9ClO6P2S
- Molecular weight
- 318.61
Names & synonyms
Show more names
Database identifiers
- CAS
89987-06-4- PubChem CID
- 60937
- DTXSID
DTXSID10237966- ChEMBL
CHEMBL1350- ChEBI
CHEBI:9598- UNII
- 6PNS59HP4Y
- EC Number
- 618-322-0
- Nikkaji
- J476.064F
Properties
Computed structural properties
- XLogP
- -0.3
- Topological polar surface area
- 140 Ų
- Hydrogen bond donors
- 4
- Hydrogen bond acceptors
- 7
- Rotatable bonds
- 4
- Heavy atoms
- 17
- Formal charge
- 0
- Complexity
- 324
Experimental & physicochemical properties
Physicochemical properties
- Melting point
- 174 · 174-177 °C
- Boiling point
- 600.7 · 600.7±65.0 °C(Predicted)
- Density
- 1.82 · 1.82±0.1 g/cm3(Predicted)
- storage temp.
- room temp
- solubility
- 2 O: · H2O: >10mg/mL, clear
- pka
- 1 · pK1 10.85; pK2 6.90; pK3 2.95; pK4 1.30(at 25℃)
- form
- powder
- color
- white to off-white
- Water Solubility
- 2 O: · H2O: >10mg/mL, clear
- InChI
- 1S/C7H9ClO6P2S.2Na.H2O/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14;;;/h1-4,7H,(H2,9,10,11)(H2,12,13,14);;;1H2/q;2*+1;/p-2
- InChIKey
- SZVJRJRMQCKFON-UHFFFAOYSA-L
- SMILES
- O.[Na+].[Na+].OP([O-])(=O)C(Sc1ccc(Cl)cc1)P(O)([O-])=O
- FDA UNII
- 6 PNS59HP4Y · 6PNS59HP4Y
- ATC code
- 5 BA05 · M05BA05
- UNSPSC Code
- 12352200 · 12352200
- NACRES
- 77 · NA.77
- WGK Germany
- 3 · 3
- Storage Class
- 11 · 11 - Combustible Solids
Safety & regulation
Toxicology
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
tiludronate
DILI Negative
Oral
DOI:10.1016/j.drudis.2019.09.022
Safety data
- wgk
- 3
- Storage Class
- 11 - Combustible Solids
Chemistry & industry
Pharmacology
ATC Code
M - Musculo-skeletal system
QM - Musculo-skeletal system
Pharmacodynamics
Tiludronic acid is a bisphosphonate that prevents osteoclasts from resorbing bone. The duration of action is quite long due to the slow clearance from the bone, and the therapeutic window is wide. Patients should be counselled regarding the risk of upper GI mucosal irritation as well as gastric and duodenal ulcers.
Mechanism of Action
Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Tiludronate inhibits protein-tyrosine-phosphatase, which increases tyrosine phosphorylation, and disrupts podosome formation. Tiludronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.
FDA Pharmacological Classification
6PNS59HP4Y
TILUDRONIC ACID
Established Pharmacologic Class [EPC] - Bisphosphonate
Chemical Structure [CS] - Diphosphonates
Tiludronic acid is a Bisphosphonate.
Absorption, Distribution and Excretion
A single 400mg dose of tiludronic acid reaches a Cmax of 3.35±1.07mg/L, with a Tmax of 1.7—0.9h, and and AUC of 27.2±9.0mg\*h/L. Tiludronic acid has an oral bioavailability of 2-11% with an average of 6%.
Tiludronic acid is 60% eliminated in the urine as the unchanged parent drug.
The volume of distribution of tiludronic acid is estimated to be between 30L and 60L. Due to the unknown clearance rate from bone, this may underestimate the true volume of distribution.
Tiludronic acid has a renal clearance of 0.68L/h in healthy subjects and 0.47L/h in subjects with Paget's disease. Approximately 50% of tilurdronic acid binds to bone but the rate of clearance from the bone is unknown.
Upstream & downstream products
Upstream raw materials
Suppliers9 total
Additional notes
DefinitionChEBI: Tiludronic acid is an organochlorine compound.
Related reactions
No reaction records under the current filter.
Linked notes
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