Conivaptan
Grundinformationen
- CAS
210101-16-9- Standard-SMILES
Cc1nc2c([nH]1)CCN(C(=O)c1ccc(NC(=O)c3ccccc3-c3ccccc3)cc1)c1ccccc1-2- InChIKey
IKENVDNFQMCRTR-UHFFFAOYSA-N- Summenformel
- C32H26N4O2
- Durchschnittliche Molmasse
- 498,6 g/mol
- Monoisotopische Masse
- 498,20557608
Überblick
Conivaptan is the amide resulting from the formal condensation of 4-[(biphenyl-2-ylcarbonyl)amino]benzoic acid with the benzazepine nitrogen of 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine. It is an antagonist for two of the three types of arginine vasopressin (AVP) receptors, V1a and V2. It is used as its hydrochloride salt for the treatment of hyponatraemia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). It has a role as an aquaretic and a vasopressin receptor antagonist.
Namen und Bezeichner
- Bevorzugter Name
- Conivaptan
- IUPAC
- N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide
- Englischer Name
- CONIVAPTAN
- Summenformel
- C32H26N4O2
- Molmasse
- 498.583
Namen und Synonyme
Conivaptan210101-16-9YM087YM-087YM 0870NJ98Y462X4'-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilideCHEBI:681850DTXSID80175220[1,1'-Biphenyl]-2-carboxamide, N-[4-[(4,5-dihydro-2-methylimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl]-(1,1'-biphenyl)-2-carboxamide, N-(4-((4,5-dihydro-2-methylimidazo(4,5-D)(1)benzazepin-6(1H)-yl)carbonyl)phenyl)-4''-((4,5-dihydro-2-methylimidazo(4,5-D)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilide
Weitere Namen anzeigen
KaunivartanZINC 12503187N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamideN-[4-[(4,5-Dihydro-2-methylimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl]-[1,1'-biphenyl]-2-carboxamide
conivaptanumN-(4-((4-methyl-3,5,9-triazatricyclo(8.4.0.0^(2,6))tetradeca-1(10),2(6),3,11,13-pentaen-9-yl)carbonyl)phenyl)-2-phenylbenzamideN-(4-(2-methyl4,5-dihydro-3H-imidazo(5,4-d)(1)benzazepine-6-carbonyl)phenyl)-2-phenylbenzamideN-[4-({4-methyl-3,5,9-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),2(6),3,11,13-pentaen-9-yl}carbonyl)phenyl]-2-phenylbenzamideN-[4-(2-methyl4,5-dihydro-3H-imidazo[5,4-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamideRefChem:56750DTXCID3097711C03XA02
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 5,7
- Polarare Oberfläche (TPSA)
- 78,1 Ų
- H-Brücken-Donoren
- 2
- H-Brücken-Akzeptoren
- 3
- Frei drehbare Bindungen
- 4
- Schwere Atome
- 38
- Formalladung
- 0
- Komplexität
- 820
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
LogP6.3
Solubility
Very slightly soluble (0.15 mg/mL at 23 °C)
1.75e-03 g/L
Physical DescriptionSolid
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
Toxikologische Informationen
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
conivaptan
DILI Negative
Intravenous
DOI:10.1016/j.drudis.2019.09.022
Chemie und Industrie
Pharmakologische Informationen
ATC Code
C - Cardiovascular system
QC - Cardiovascular system
Protein Binding99%
Pharmacodynamics
Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V<sub>1A</sub> and V<sub>2</sub> receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V<sub>2</sub> receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular <sub>1A</sub> receptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V<sub>2</sub> antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V<sub>1A</sub> receptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.
Mechanism of Action
Conivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin V<sub>1A</sub> and V<sub>2</sub> receptors <i>in vitro</i>. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.
Biological Half-Life5 hours
Metabolism/Metabolites
CYP3A4 is the sole cytochrome P450 isozyme responsible for the metabolism of conivaptan. Four metabolites have been identified. The pharmacological activity of the metabolites at V<sub>1a</sub> and V<sub>2</sub> receptors ranged from approximately 3-50% and 50-100% that of conivaptan, respectively.
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