913611-97-9 Usage
Description
Brexpiprazole is a novel atypical antipsychotic drug that serves as a serotonin-dopamine activity modulator. It is a dopamine D2 receptor partial agonist and exhibits unique pharmacological properties, acting as a partial agonist of serotonin 5-HT1A and dopamine D2 receptors, and as a full antagonist of 5-HT2A and noradrenaline α1B/2C receptors. Developed by Otsuka and Lundbeck, it was approved by the FDA in 2015 for the treatment of schizophrenia and as an adjunctive treatment for depression. Brexpiprazole is considered a successor to Otsuka’s antipsychotic drug aripiprazole (trade name Abilify) and has shown potential in ameliorating PCP-induced cognitive deficits in mice via 5-HT1A receptors.
Uses
Used in Psychiatry:
Brexpiprazole is used as an atypical antipsychotic for the treatment of schizophrenia, a chronic mental disorder characterized by delusions, hallucinations, and disorganized thinking. Its unique pharmacological profile allows for efficacy and tolerability over established treatments.
Used in Depression Treatment:
Brexpiprazole is used as an adjunctive treatment for major depressive disorder (MDD), a mood disorder characterized by persistent feelings of sadness, hopelessness, and a lack of interest in activities. It has demonstrated efficacy in improving symptoms and providing an alternative to conventional treatments.
Used in CNS Disorders:
Brexpiprazole is used as a drug candidate for the treatment and prevention of mental disorders, including central nervous system (CNS) disorders. Its multi-receptor pharmacology offers potential benefits in managing various psychiatric conditions.
Used in Cognitive Deficit Amelioration:
Brexpiprazole has shown potential in preclinical studies as a treatment to ameliorate cognitive deficits induced by phencyclidine (PCP) in mice, suggesting a possible application in improving cognitive function in certain conditions via 5-HT1A receptors.
References
https://en.wikipedia.org/wiki/Brexpiprazole
https://www.drugbank.ca/drugs/DB09128
Maeda, K, et al. "Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator." Journal of Pharmacology & Experimental Therapeutics 350.3(2014):589-604.
Maeda, K, et al. "Brexpiprazole II: antipsychotic-like and procognitive effects of a novel serotonin-dopamine activity modulator." Journal of Pharmacology & Experimental Therapeutics 350.3(2014):605.
Yoshimi, N, et al. "Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors. " Pharmacology Biochemistry & Behavior 124(2014):245.
Synthesis
Commercially available fluorobenzaldehyde (60) underwent
a substitution reaction with commercial tert-butyl piperazine-1-
carboxylate (61) under basic conditions to afford the
piperazinyl benzaldehyde 62 in excellent yield. Next, the
construction of the benzothiophene was affected by initial
condensation of thioglycolic acid ethyl ester 63 with ochlorobenzaldehyde
62 under mildly basic conditions at
elevated temperatures. Treatment with aqueous base and
adjustment of pH to roughly 5 through the use of 4 N HCl
furnished the 2-carboxylic acid benzothiophene 64 in 80% yield
across the three-step operation. Next, decarboxylation through
the use of cuprous oxide using conditions slightly modified
from those originally described by Goosen followed by acidic
removal of the Boc protecting group on the terminal piperazine
nitrogen secured the key piperazinyl benzothiophene subunit
65 as the corresponding hydrochloride salt.
The hydroxyquinolone and linker component synthesis
began with alkylation of commercially available quinolone 66
with 1,4-bromochlorobutane (67) under basic conditions to
furnish chloroalkoxyquinolone 68. A subsequent alkylation with
hydrochloride salt 65 using potassium carbonate and warm
aqueous ethanol followed by recrystallizative workup resulted
in clean conversion to brexpiprazole (VIII) in 78% yield from
68.
Enzyme inhibitor
This serotonin-dopamine activity modulator, or SDAM (FW = 433.60 g/mol; CAS 913611-97-9), also known as OPC-34712, Rexulti?, 7-{4-[4-(1- benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one, is an atypical antipsychotic drug that acts as a dopamine D2L (Ki = 1.1 nM) and D3 (Ki = 0.3 nM) receptor partial agonist and a partial agonist of 5-HT1A receptors (Ki = 0.12 nM). Brexpiprazole is also an antagonist of the 5-HT2A (Ki = 0.47 nM), 5-HT2B (Ki = 1.9 nM), 5-HT7 (Ki = nM), α1B-adrenergic (Ki = 0.17 nM), α2C-adrenergic (Ki = 0.59 nM), and histamine H1 receptors (Ki = 19 nM). It has negligible affinity for the mACh receptors. Rexulti is an FDA-approved add-on medication for major depressive disorder in adults. See Aripiprazole
Check Digit Verification of cas no
The CAS Registry Mumber 913611-97-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,1,3,6,1 and 1 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 913611-97:
(8*9)+(7*1)+(6*3)+(5*6)+(4*1)+(3*1)+(2*9)+(1*7)=159
159 % 10 = 9
So 913611-97-9 is a valid CAS Registry Number.
913611-97-9Relevant articles and documents
Large-steric-hindrance N-heterocyclic carbene palladium complex, preparation method and application thereof, and synthesis method of sonidegib based on large-steric-hindrance N-heterocyclic carbene palladium complex
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Paragraph 0195; 0208-0210, (2021/01/24)
The invention belongs to the technical field of organic synthesis and chemical catalysis, and discloses a large-steric-hindrance N-heterocyclic carbene palladium complex, a preparation method thereof,an application of the complex in efficient catalysis of a C-N coupling reaction under a room-temperature air condition, and a synthesis method of sonidegib based on the complex. According to the large-steric-hindrance N-heterocyclic carbene palladium complex, diphenyl imidazole serves as a main ligand framework, functionalized allyl serves as an auxiliary ligand, the functionalized allyl is introduced beside a metal center of a catalyst to serve as an auxiliary ligand, the catalytic activity and stability are remarkably improved, the large-steric-hindrance N-heterocyclic carbene palladium complex can be applied to efficient catalysis of a CN coupling reaction, particularly, the CN coupling reaction can be efficiently catalyzed under the room temperature condition, and the yield can reachup to 99%. The invention also provides a method for synthesizing sonidegib by taking aryl/aliphatic amine and aryl chloride as reactants and a three-step method at room temperature under the catalysisof a palladium catalytic system, the synthetic method has few steps, and the total yield can reach 74.5%.
Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone
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, (2021/05/05)
The invention belongs to the field of chemical engineering, and particularly relates to a preparation method of a brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone. According to the novel method for preparing the 7-hydroxy-1H-quinoline-2-ketone, DDQ is replaced with palladium on carbon, the obtained product is high in yield, few in impurity and easy to operate, the catalyst can be recycled, a target compound is synthesized through direct catalytic dehydrogenation, and the method has green atom economy and is suitable for industrial production.
Preparation method and application of substituted quinoline-2(1H)-one compound
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Paragraph 0085-0088, (2019/11/29)
The invention belongs to the field of pharmaceutical chemistry and chemical synthesis, and concretely relates to a preparation method of a substituted quinoline-2(1H)-one compound. The invention provides a preparation method of the substituted quinoline-2(1H)-one compound. The preparation method performs an oxidation reaction on a compound represented by a formula I and an oxidant in a solvent toobtain a compound represented by a formula II. The preparation method has the advantages of simple method, high yield and low cost and is suitable for industrial production. The substituted quinoline-2(1H)-one represented by the formula II is an important intermediate of a variety of pharmaceutical active ingredients.