1083076-69-0 Usage
Description
Cariprazine
hydrochloride (IX) is an oral, brain-penetrant, atypical
antipsychotic developed by the Hungarian pharmaceutical
firm Gedeon Richter. It was approved by the FDA in September 2015 for treatment of schizophrenia and for the
acute treatment of manic or mixed episodes of bipolar I
disorder. While the precise mechanism of action of
cariprazine is unknown, its antipsychotic and procognitive
effects may be mediated through partial agonism at dopamine
D2/D3 and serotonin 5-HT1A receptors as well as antagonism
at serotonin 5-HT2A receptors. Unlike many antipsychotics,
cariprazine displays particular selectivity for the D3 receptor
(D3, Ki = 0.085 nM; D2L, Ki = 0.49 nM; D2S, Ki = 0.69 nM).
Cariprazine is extensively metabolized by CYP3A4 and, to a
lesser extent, CYP2D6; desmethyl and didesmethyl cariprazine,
the primary metabolites, are pharmacologically equipotent to
the parent drug. In clinical trials, cariprazine demonstrated
improvement compared to placebo as measured by
Young Mania Rating Scale (YMRS) total scores in patients with
bipolar mania and by Positive and Negative Syndrome Scale
(PANSS) total scores in patients with schizophrenia. Forest
Laboratories (now Allergan) has exclusive rights to cariprazine
in the U.S. and Canada, while Mitsubishi Pharma Corporation
has exclusive rights to the sale of the drug in Japan and Asia.
Definition
ChEBI: A hydrochloride obtained by combining cariprazine with one molar equivalent of hydrochloric acid. Used for treatment of schizophrenia and bipolar disorder.
Synthesis
While the synthesis of cariprazine hydrochloride has been
reported in a number of patents as well as its discovery
synthesis in the publicly disclosed literature, the process route
has not yet been disseminated. Starting with the reduction of commercial 2-(4-
nitrophenyl)acetic acid (69) via hydrogenation in water in
the presence of Pd/C, this reaction proceeds a one-pot,
stepwise reduction of the nitro group. A separate reduction
event converting the phenyl ring to the corresponding
cyclohexane provides 4-aminocyclohexylacetic acid with 60-70% selectivity for the desired trans isomer. Following filtration
and distillation, the crude aqueous solution was treated with
HCl in refluxing ethanol to generate the corresponding ethyl
ester 70. Crystallization from acetonitrile gave the HCl salt in
high purity and 40% yield over two steps (a reaction sequence
that was reported on 200 kg scale). Amine 70 was transformed
into intermediate 73 via Boc protection followed by ester
reduction to the primary alcohol 71, which was obtained as a
solution in toluene following extraction. Next, mesylation of the
alcohol followed by alkylation with commercially available
piperazine 72 provided piperazinyl cyclohexane 73 in 70% over
the four-step sequence. The carbamate protecting group within
73 was removed via acidic ethanolysis, and the resulting
product was treated with triphosgene and dimethylamine to
generate cariprazine as the freebase. Salt formation by means of
methanolic HCl ultimately furnished cariprazine hydrochloride
IX in 85% yield from 73.
Check Digit Verification of cas no
The CAS Registry Mumber 1083076-69-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,8,3,0,7 and 6 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1083076-69:
(9*1)+(8*0)+(7*8)+(6*3)+(5*0)+(4*7)+(3*6)+(2*6)+(1*9)=150
150 % 10 = 0
So 1083076-69-0 is a valid CAS Registry Number.
1083076-69-0Relevant articles and documents
A PROCESS FOR THE PREPARATION OF CARIPRAZINE SALT
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Page/Page column 13; 19, (2021/02/05)
A process for the preparation of cariprazine hydrochloride (Formula I) by reacting trans-4-{2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl}cyclohexanamine (Formula II) or it's salt with N,N-dimethylcarbamoyl chloride (Formula III) in a biphasic solvent system containing an organic solvent phase and an aqueous phase, in the presence of a base.
NOVEL SALTS OF PIPERAZINE COMPOUNDS AS D3/D2 ANTAGONISTS
-
Page/Page column 7, (2009/02/11)
The present invention relates to novel monohydrochloride, dihydrochloride, monohydrobromide, maleate and methanesulphonate salts of trans 4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine and/or their hydrates and/
