150683-30-0 Usage
Description
Different sources of media describe the Description of 150683-30-0 differently. You can refer to the following data:
1. Tolvaptan(trade names Samsca and Jinarc) is an oral selective vasopressin antagonist developed by Otsuka for the treatment of hyponatremia, and it is a non-peptide selective antidiuretic hormone receptor antagonist. The drug can increase the concentration of sodium ions in the plasma, and help the excess water discharge from the urine. The drug could enhance the ability of the kidney to deal with water, and significantly reduce the weight and edema of patients while not accompanied by increased electrolyte excretion, without destroying the blood electrolyte balance. The drug can be used to treat hyponatremia caused by congestive heart failure, various edematous diseases, cirrhosis and antidiuretic hormone deficiency syndrome. The study found that, when the plasma sodium concentration decreased, in order to maintain the balance of sodium concentration inside and outside the cell, extracellular fluid will enter the cell, so the cells will swell. When the brain cells swell, it will lead to a variety of hyponatremia symptoms, including dizziness, weakness, headache, nausea, confusion, consciousness and convulsions. Severe hyponatremia can lead to coma and death. There is no corresponding study of tolvaptan tablets in patients with severe hyponatremia.
2. Tolvaptan is a nonpeptide vasopressin V2 receptor antagonist (IC50 = 3 nM for rat receptor) and a diuretic agent. It is selective for V2 over V1 receptors (IC50 = 0.58 μM). Tolvaptan increases urine volume by 3-fold in rats when administered at a dose of 0.54 mg/kg. It also reduces left ventricular end-systolic volumes and improves left ventricular ejection fraction in a rat model of myocardial infarction. Formulations containing tolvaptan have been used to treat hyponatremia.
3. 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
<135 mmol/L). This electrolyte imbalance increases mortality rates by
60-fold. Selective antagonism of the AVP V2receptor 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
<125 mmol/L or less distinct hyponatremia that is symptomatic and
has resisted correction with fluid restriction).
As a more potent and
selective V2 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.
.
Synthesis
Different sources of media describe the Synthesis of 150683-30-0 differently. You can refer to the following data:
1. Fugure 1: Synthesis of Tolvaptan
2. Tolvaptan may be prepared in 11 steps starting from 5chloro- 2-nitrobenzoic acid. Following esterification, reduction of the nitro moiety with tin(II) chloride, subsequent protection (tosylation) and alkylation of the resulting aniline, and a Dieckmann cyclization with potassium tert-butoxide generate the benzazepinone core that is ultimately decarboxylated by heating with hydrochloric acid in acetic acid. After deprotection of the amine group, condensation with 2methyl- 4-nitrobenzoyl chloride affords another nitro handle that is reduced with tin(II) chloride. This aniline is coupled with 2-methylbenzoyl chloride to give the penultimate intermediate. In the final step, reduction of the ketone functionality with sodium borohydride provides racemic tolvaptan that is formulated into 15- and 30-mg tablets for oral administration.
Precautions
Tolvaptan(SAMSCA) should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.
Tolvaptan(SAMSCA) is contraindicated in the following conditions:
Urgent need to raise serum sodium acutely
Inability of the patient to sense or appropriately respond to thirst
Hypovolemic hyponatremia
Concomitant use of strong CYP 3A inhibitors
Anuric patients
Hypersensitivity (e.g. anaphylactic shock, rash generalized) to tolvaptan or its components
References
https://www.samsca.com/dosing-and-administration
https://en.wikipedia.org/wiki/Tolvaptan
Chemical Properties
White Solid
Originator
Otsuka Pharmaceutical (US)
Uses
Different sources of media describe the Uses of 150683-30-0 differently. You can refer to the following data:
1. Tolvaptan (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) assoc
2. Labelled Tolvaptan
s, and the syndrome of inappropriate antidiuretic hormone (SIADH).
3. It is a selective, competitive arginine vasopressin V2 receptor antagonist
f inappropriate antidiuretic hormone (SIADH).
Brand name
Samsca
Biochem/physiol Actions
Tolvaptan (OPC 41061) is a potent, orally active non-peptide vasopressin V2 selective antagonist. IC50 = 3 nM at the rat V2 receptor; 29 times more selective for the V2 than for V1a. Tolvaptan has also been shown to inhibit the development of polycystic kidney disease in several animal models.
Clinical Use
Tolvaptan, also known as OPC-41061, is a selective, competitive
arginine vasopressin receptor 2 antagonist used to treat hyponatremia
(low blood sodium levels) associated with congestive heart
failure, cirrhosis, and the syndrome of inappropriate antidiuretic
hormone (SIADH). Otsuka Pharmaceutical licensed tolvaptan
under the trade name Samsca after the FDA approved the drug in
May 2009. Tolvaptan has also shown efficacy against polycystic
kidney disease. In a 2004 trial, tolvaptan administered with traditional
diuretics was noted to increase excretion of excess fluids and
improve blood sodium levels in patients with heart failure without
producing side effects such as hypotension (low blood pressure) or
hypokalemia (decreased blood levels of potassium). The drug also
exhibited no adverse effect on kidney function.
Side effects
The most common adverse events were thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia. The recommended starting dose is 15 mg daily with a daily 15-mg adjustment to a maximum of 60 mg daily to raise serum sodium concentration. Initiation should be in a hospital setting where serum sodium and volume status may be monitored since too rapid correction of hyponatremia (>12 mEq/L/24 h) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, spastic quadriparesis, seizures, coma, and death. In addition to avoiding concomitant use of strong CYP3A4 inhibitors, tolvaptan is contraindicated in settings of urgent need to raise serum sodium acutely, in patients with an inability to sense or appropriately respond to thirst, in hypovolemic hyponatremia conditions, and in anuric patients.
references
[1] miyazaki t, fujiki h, yamamura y, et al. tolvaptan, an orally active vasopressin v2-receptor antagonist-pharmacology and
Check Digit Verification of cas no
The CAS Registry Mumber 150683-30-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,0,6,8 and 3 respectively; the second part has 2 digits, 3 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 150683-30:
(8*1)+(7*5)+(6*0)+(5*6)+(4*8)+(3*3)+(2*3)+(1*0)=120
120 % 10 = 0
So 150683-30-0 is a valid CAS Registry Number.
InChI:InChI=1/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31)/t24-/m1/s1
150683-30-0Relevant articles and documents
INTERMEDIATES AND METHODS FOR THE PREPARATION OF TOLVAPTAN AND ITS DERIVATIVES
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, (2021/12/31)
The present invention relates to new intermediates for the synthesis of tolvaptan and its derivatives, as well as a method for its preparation involving said intermediates.
MANUFACTURING METHOD OF TOLVAPTAN, SALT THEREOF AND SOLVATE
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, (2020/04/18)
PROBLEM TO BE SOLVED: To provide a manufacturing method of high purity and high yield tolvaptan, a salt thereof, or a solvate thereof without using a solvent with large environmental load, and having enhanced operability of a reaction. SOLUTION: There is provided a manufacturing method of tolvaptan, a salt thereof, or a solvate thereof, including a process for reacting following a described carboxylic acid derivative (I) with a chlorination agent such as thionyl chloride to convert it to a corresponding acid chloride (I), in which the reaction process is conducted in a presence of a solvent having relative dielectric constant of 10 or more and donor number of 20 or more, and represented by N,N-dimethyl acetamide, N-methyl-2-pyrrolidone, N.N'-dimethyl propylene urea or N,N,N',N'-tetramethyl urea. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Preparation method of high-purity tolvaptan
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Paragraph 0023; 0024; 0025; 0026; 0027; 0028, (2018/03/01)
The invention discloses a preparation method of high-purity tolvaptan. The preparation method comprises the step of reducing N-[4-[(5R)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1-benazepine-1-formyl]-3-methyl phenyl]-2-methyl benzamide with sodium bis(2-methoxyethoxy) aluminumhydride, thereby obtaining the high-purity tolvaptan with the purity higher than or equal to 99.95%. The preparation method disclosed by the invention has the advantages that sodium bis(2-methoxyethoxy) aluminumhydride is adopted as a reducing agent for preparing tolvaptan by reducing N-[4-[(5R)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1-benazepine-1-formyl]-3-methyl phenyl]-2-methyl benzamide, the production of a dechlorination impurity IV can be extremely effectively inhibited, and finally the high-purity tolvaptan with the purity higher than or equal to 99.95% can be obtained, and high yield being 90% or above can be obtained while tetrahydrofuran or methyltetrahydrofuran is adopted as a reaction solvent.
