168079-32-1

168079-32-1 structure

Name: Lixivaptan
Chemical Name: N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methylbenzamide
CAS Number: 168079-32-1
Molecular Formula: C₂₇H₂₁ClFN₃O₂
Molecular Weight: 473.926
Catalog: Signaling Pathways GPCR/G Protein Vasopressin Receptor
Create Date: 2018-02-28 08:00:00
Modify Date: 2024-01-02 10:24:56
Lixivaptan (VPA-985, WAY-VPA 985) is an orally active and selective vasopressin receptor V2 antagonist, with IC50 values of 1.2 and 2.3 nM for human and rat V2, respectively.

Name	N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methylbenzamide
Synonyms	N-[3-Chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide WAY-VPA-985 VPA-985 Benzamide, N-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methyl- lixivaptan UNII-8F5X4B082E

Description	Lixivaptan (VPA-985, WAY-VPA 985) is an orally active and selective vasopressin receptor V2 antagonist, with IC50 values of 1.2 and 2.3 nM for human and rat V2, respectively.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> Vasopressin Receptor Research Areas >> Cardiovascular Disease
Target	IC50: 1.2 nM (human V2), 2.3 nM (rat V2)[1]
In Vitro	Lixivaptan displays competitive antagonist activity at V2 receptors[1].
In Vivo	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 Uvol over the AVP-treated vehicle group by 438, 1018, and 1133%, respectively, while Uosm 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[1]. 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[2].
References	[1]. Albright JD, et al. 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors. J Med Chem. 1998 Jul 2;41(14):2442-4. [2]. Ghali JK, et al. Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia. IDrugs. 2010 Nov;13(11):782-92.

Density	1.3±0.1 g/cm3
Boiling Point	626.5±55.0 °C at 760 mmHg
Molecular Formula	C₂₇H₂₁ClFN₃O₂
Molecular Weight	473.926
Flash Point	332.7±31.5 °C
Exact Mass	473.130646
PSA	57.83000
LogP	7.23
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.658