Tolvaptan
N-(4-(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carbonyl)-3-Methylphenyl)-2-MethylbenzaMide · SaMsca · N-(4-(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]-azepine-1-carbonyl)-3-methylphenyl)-2- · 7-Chloro-5-hydroxy-1-(2-methyl-4-(2-methylbenzoylamino)benzoyl)2,3,4,5-tetrahydro-1H-1-benzazepine · N-[4-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methyl-benzamide · N-[4-(9-chloro-6-hydroxy-2-azabicyclo[5.4.0]undeca-8,10,12-triene-2-carbonyl)-3-methyl-phenyl]-2-methyl-benzamide · Tolvptan · olvaptan
Identifikatoren & physikalische Daten
| CAS No. | 150683-30-0 |
|---|---|
| Summenformel | C26H25ClN2O3 |
| Durchschnittliche Molmasse | 448,9 g/mol |
| Monoisotopische Masse | 448,15537034 g/mol |
| SMILES | Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(O)c3cc(Cl)ccc32)c(C)c1 |
| InChIKey | GYHCTFXIZSNGJT-UHFFFAOYSA-N |
| PubChem CID | 216237 |
| ChEMBL | CHEMBL344159 |
| ChEBI | CHEBI:32246 |
| EC No. | 691-537-5 |
| DTXSID | DTXSID3048780 |
Chemische & physikalische Eigenschaften
| XLogP | 4,8 |
|---|---|
| Polarare Oberfläche (TPSA) | 69,6 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 32 |
| Formalladung | 0 |
| Komplexität | 673 |
| Color/Form | Colorless prisms |
| Human Drugs | FDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| Schmelzpunkt | 225.9 °C219-222°C |
| Stability/Shelf Life | Stable under recommended storage conditions. |
| Siedepunkt | 594.4±50.0 °C(Predicted) |
| Dichte | 1.311±0.06 g/cm3(Predicted) |
| Lagerbedingungen | 2-8°C |
| Löslichkeit | DMSO: ≥15mg/mL |
| pKa (Säurekonstante) | 13.00±0.70(Predicted) |
| Aggregatzustand | powder |
| Farbe | white to tan |
| InChIKey | GYHCTFXIZSNGJT-UHFFFAOYSA-N |
| SMILES | C(NC1=CC=C(C(N2C3=CC=C(Cl)C=C3C(O)CCC2)=O)C(C)=C1)(=O)C1=CC=CC=C1C |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]P203, P260, P263, P264, P270, P280, P318, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 4 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H413: May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]P273, and P501 (click each P-code to see the statement) |
|---|---|
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including tolvaptan, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Hazard Classes and Categories | Repr. 2 (100%) |
| Hazardous Reactivities and Incompatibilities | Strong oxidizing agents. |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advise for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
| Lagerbedingungen | Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2-8 °C. |
| Reinigungsverfahren | Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
Anwendungen & Verwendung
Beschreibung
The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-proteincoupled receptor subtypes:V1-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration 2receptor promotes water excretion without perturbing electrolyte balance making it an appealing target for preventing disease progression. Following the introduction of the dual AVP V1a/V2 receptor antagonist conivaptan, tolvaptan has recently been launched as a nonpeptide, selective V2 receptor antagonist with potent aquaretic attributes for the treatment of hypervolemic and euvolemic hyponatremia (serum sodium concentration of 2 receptor antagonist, tolvaptan is a follow-up to mozavaptan, which possesses weak V1 receptor antagonism and was approved for the treatment of SIADH in Japan. .
History
Tolvaptan was discovered by Otsuka Pharmaceutical Co., Ltd. (Otsuka). In May 2009, tolvaptan (Samsca; Otsuka) was approved by the US FDA for the treatment of clinically significant hypervolaemic and euvolaemic hyponatraemia. The U.S. Food and Drug Administration (FDA) granted tolvaptan a fast track designation for clinical trials investigating its use for the treatment of polycystic kidney disease. The FDA granted Jynarque an orphan drug designation in April 2012, for the treatment of autosomal dominant polycystic kidney disease.
Verwenden
Labelled Tolvaptan s, and the syndrome of inappropriate antidiuretic hormone (SIADH).