Tolvaptan

Names

[ Name ]:
Tolvaptan

[Synonym ]:
(±)-4'-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-o-tolu-m-toluidide
Tolvaptan
UNII-21G72T1950
olvaptan
N-{4-[(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl}-2-methylbenzamide
Benzamide, N-[4-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methyl-
Samsca
benzazepine derivative,32
N-[4-(9-chloro-6-hydroxy-2-azabicyclo[5.4.0]undeca-8,10,12-triene-2-carbonyl)-3-methyl-phenyl]-2-methyl-benzamide

Biological Activity

[Description]:

Tolvaptan is a selective, competitive arginine vasopressin receptor 2 antagonist with an IC50 of 1.28μM for the inhibition of AVP-induced platelet aggregation.IC50 value: 1.28 uM (inhibition of AVP-induced platelet aggregation)Target: vasopressin receptor 2Tolvaptan (OPC-41061) is a selective, competitive arginine vasopressin receptor 2 antagonist with an IC50 of 1.28μM for the inhibition of AVP-induced platelet aggregation. Tolvaptan (OPC-41061) is used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan (OPC-41061) is also in fast-track clinical trials for polycystic kidney disease. Treatment with t tolvaptan (OPC-41061) causes rapid and sustained body weight reductions concurrent with increases in urine output, improves and/or normalizes serum sodium in hyponatremic patients, reduces signs and symptoms of congestion and increases thirst. However, tolvaptan (OPC-41061) has not been shown to decrease heart failure re-hospitalization or mortality. As an adjunct to standard therapy, tolvaptan (OPC-41061) is unique in that it is virtually the only novel agent tested in patients hospitalized for acute heart failure syndrome (AHFS) to reach its primary end point for short-term efficacy without causing deleterious side effects.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> GPCR/G Protein >> Vasopressin Receptor

Research Areas >> Cardiovascular Disease

[References]

[1]. Friedman B, Cirulli J.Hyponatremia in critical care patients: Frequency, outcome, characteristics, and treatment with the vasopressin V(2)-receptor antagonist tolvaptan.J Crit Care. 2012 Aug 8.

[2]. Inomata T.Tolvaptan (vasopressin receptor antagonist).Nihon Rinsho. 2011 Nov;69 Suppl 9:408-11.

[3]. Vaduganathan M, Gheorghiade M, Pang PS, Konstam MA, Zannad F, Swedberg K, Grinfeld L, Burnett JC Jr, Krasa HB, Zimmer C, Blair J, Ouyang J, Maggioni AP; EVEREST investigators.Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment.J Cardiovasc Med (Hagerstown). 2012 Jul;13(7):415-22.

[4]. Y Yamamura et al. OPC-41061, a Highly Potent Human Vasopressin V2-Receptor Antagonist: Pharmacological Profile and Aquaretic Effect by Single and Multiple Oral Dosing in Rats. J. Pharmacol. Exp. Ther. 1998, 287(3), 860-867.

[5]. RW Schrier et al. Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia. N Engl J Med 2006, 355, 2099-2112.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
594.4±50.0 °C at 760 mmHg

[ Melting Point ]:
219-222°C

[ Molecular Formula ]:
C₂₆H₂₅ClN₂O₃

[ Molecular Weight ]:
448.941

[ Flash Point ]:
313.3±30.1 °C

[ Exact Mass ]:
448.155365

[ PSA ]:
69.64000

[ LogP ]:
4.09

[ Appearance of Characters ]:
white to tan

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.664

[ Storage condition ]:
Refrigerator

[ Water Solubility ]:
DMSO: ≥15mg/mL

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Relation of serum uric acid levels and outcomes among patients hospitalized for worsening heart failure with reduced ejection fraction (from the efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan trial).

Am. J. Cardiol. 114(11) , 1713-21, (2014)

We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) ≤40%, with...

Tolvaptan plus pasireotide shows enhanced efficacy in a PKD1 model.

J. Am. Soc. Nephrol. 26(1) , 39-47, (2015)

Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of ESRD. A central defect associated with ADPKD pathology is elevated levels of 3', 5'-cyclic AMP (cAMP). Compounds such as tolv...

Association of arginine vasopressin levels with outcomes and the effect of V2 blockade in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial.

Circ. Heart Fail. 6(1) , 47-52, (2013)

Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between...