913611-97-9 Usage
Description
Different sources of media describe the Description of 913611-97-9 differently. You can refer to the following data:
1. Brexpiprazole is a kind of atypical antipsychotic. It is a dopamine D2 receptor partial agonist. As a novel serotonin-dopamine activity modulator, it can be used for the treatment of schizophrenia, and for the adjunctive treatment for depression. It can also provide efficacy and tolerability over established adjunctive treatments formajor depressive disorder(MDD).Recent study has also suggested it can ameliorate PCP-induced cognitive deficits in mice via 5-HT1A receptors.
2. Brexpiprazole is a novel
antipsychotic drug which serves as a serotonin ? dopamine
activity modulator and has demonstrated efficacy as an
adjunctive treatment in patients with major depressive disorder
(MDD). The drug exhibits a unique pharmacological profile,
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, with similar subnanomolar
binding affinity. The drug, which was developed by Otsuka
and Lundbeck, was approved in 2015 by the FDA for the
treatment of schizophrenia and as an adjunctive treatment for
depression. Brexpiprazole is widely considered to be a
successor to Otsuka’s antipsychotic drug aripiprazole (trade
name Abilify) whose patent expired in August 2014.
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.
Uses
Brexpiprazole is a drug candidate useful in treatment and prevention of mental disorders including CNS disorders.
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
-
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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Paragraph 0028; 0070-0073, (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.
Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole
Chen, Weiming,Suo, Jin,Liu, Yongjian,Xie, Yuanchao,Wu, Mingjun,Zhu, Fuqiang,Nian, Yifeng,Aisa, Haji A.,Shen, Jingshan
, p. 852 - 857 (2019/04/01)
Efforts toward route evaluation and process optimization for the preparation of brexpiprazole (1) are described. Starting from commercially available dihydroquinolinone 11, a three-step synthesis route composed of O-alkylation, oxidation, and N-alkylation was selected for industry-oriented process development aiming to reduce side reactions and achieve better impurity profiles. The reaction conditions of the three steps were investigated, and the control strategy for the process-related impurities was established. The optimized process was validated on the kilogram scale and now is viable for commercialization, with the results of not less than 99.90% purity of 1 (by HPLC) and not more than 0.05% of persistent impurities 15 and 16.