Name | Lixivaptan |
Synonyms | VPA985 VPA-985 VPA 985 Lixivaptan LIXIVAPTAN WAY-VPA-985 LIXIVAPTAN (VPA 985) Lixivaptan (VPA-985) N-[3-Chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide N-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide N-[3-Chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepine-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide BenzaMide,N-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-Methyl- N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methyl-benzamide N-[3-Chloro-4-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide |
CAS | 168079-32-1 |
InChI | InChI=1/C27H21ClFN3O2/c1-17-8-9-19(29)13-23(17)26(33)30-20-10-11-22(24(28)14-20)27(34)32-16-21-6-4-12-31(21)15-18-5-2-3-7-25(18)32/h2-14H,15-16H2,1H3,(H,30,33) |
InChIKey | PPHTXRNHTVLQED-UHFFFAOYSA-N |
Molecular Formula | C27H21ClFN3O2 |
Molar Mass | 473.93 |
Density | 1.32 |
Melting Point | >114°C (dec.) |
Boling Point | 626.5±55.0 °C(Predicted) |
Flash Point | 332.7°C |
Solubility | DMSO: soluble20mg/mL, clear |
Vapor Presure | 1.3E-15mmHg at 25°C |
Appearance | powder |
Color | white to beige |
pKa | 11.86±0.70(Predicted) |
Storage Condition | Sealed in dry,Room Temperature |
Refractive Index | 1.657 |
In vitro study | Lixivaptan displays competitive antagonist activity at V2 receptors. |
In vivo study | In conscious dogs, water-loaded with 30 mL/kg (po) and arginine vasopressin (AVP)-treated (0.4 µg/kg in oil, sc), lixivaptan (1, 3, and 10 mg/kg po) increases U vol over the AVP-treated vehicle group by 438, 1018, and 1133%, respectively, while U osm decreases from 1222 mOsm/kg (water-loaded and AVP treated vehicle) to 307, 221, and 175 mOsm/kg, respectively. In homozygous Brattleboro rats lacking AVP, lixivaptan at 10 mg/kg po (i.e., 10 times the dose producing V2 antagonist activity) b.i.d. for 5 days, shows a sustained antagonist action without evidence of agonist effects. In a randomized double-blind placebo-controlled ascending single dose study, patients (deprived of fluids overnight before dosing) are dosed orally with 30, 75, or 150 mg of lixivaptan. All three doses increase urine flow and serum sodium concentrations and produced significant dose-related decreases in urinary osmolality. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system. |
WGK Germany | 3 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.11 ml | 10.55 ml | 21.1 ml |
5 mM | 0.422 ml | 2.11 ml | 4.22 ml |
10 mM | 0.211 ml | 1.055 ml | 2.11 ml |
5 mM | 0.042 ml | 0.211 ml | 0.422 ml |