Category: 839712-12-8

Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies was written by Marder, Stephen;Fleischhacker, W. Wolfgang;Earley, Willie;Lu, Kaifeng;Zhong, Yan;Nemeth, Gyorgy;Laszlovszky, Istvan;Szalai, Erzsebet;Durgam, Suresh. And the article was included in European Neuropsychopharmacology in 2019.Synthetic Route of C21H32Cl2N4O This article mentions the following:

Schizophrenia affects various symptom domains, including pos. and neg. symptoms, mood, and cognition. Cariprazine, a dopamine D₃/D₂ receptor partial agonist and serotonin 5-HT_1A receptor partial agonist, with preferential binding to D₃ receptors, is approved for the treatment of adult patients with schizophrenia and mania associated with bipolar I disorder. Post hoc analyses evaluated mean change from baseline to week 6 in PANSS-derived symptom factors (pos. symptoms, neg. symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression) and PANSS single items for cariprazine vs. placebo. P values were not adjusted for multiple comparisons. At week 6, statistically significant differences vs. placebo were seen for cariprazine on all 5 PANSS factors (P < 0.01 all). Effects sizes ranged from 0.21 (anxiety/depression) to 0.47 (disorganized thought). Dose-response anal. from the fixed-dose studies found significant differences for all cariprazine doses (1.5, 3.0, 4.5, and 6.0 mg/d) vs. placebo in PANSS total score, and in neg. symptom and disorganized thought factor scores (P < 0.001). Differences between cariprazine and placebo were also statistically significant on 26 of 30 PANSS single items (P < 0.05). In these post hoc analyses, cariprazine was effective vs. placebo in improving all 5 PANSS factor domains, suggesting that it may have broad-spectrum efficacy in patients with acute schizophrenia. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Synthetic Route of C21H32Cl2N4O).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Synthetic Route of C21H32Cl2N4O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

[Cariprazine, a new type – dopamine D₃ receptor preferring – partial agonist atypical antipsychotic for the treatment of schizophrenia and the primary negative symptoms]. was written by Laszlovszky, Istvan;Kiss, Bela;Barabassy, Agota;Kapas, Margit;Nemeth, Gyorgy. And the article was included in Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja in 2019.Recommanded Product: 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea This article mentions the following:

Dopamine D₂ receptor partial agonists represent a new generation of atypical antipsychotics. Cariprazine, which has received centralized market authorization from the European Medicines Agency in 2017 for the treatment of adult patients with schizophrenia (including those with predominant negative symptoms of schizophrenia) differs from the other two partial agonist antipsychotics aripiprazole and brexpiprazole due to its unique features. Cariprazine is a dopamine D₃ preferring D₃/D₂ partial agonist with very similar dopamine receptor subtype selectivity as dopamine. It has proven efficacy in the treatment of positive and negative symptoms of schizophrenia, as well as for relapse prevention. Further phase-3 clinical studies proved the efficacy of cariprazine in the acute treatment of manic or mixed episodes associated with bipolar I disorder, as well as in bipolar depression. For the adjunctive treatment of major depressive disorder, phase 3 studies are in progress. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Recommanded Product: 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Recommanded Product: 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Binding kinetics of cariprazine and aripiprazole at the dopamine D₃ receptor was written by Frank, Annika;Kiss, Dora J.;Keseru, Gyoergy M.;Stark, Holger. And the article was included in Scientific Reports in 2018.Computed Properties of C21H32Cl2N4O This article mentions the following:

The dissociation behaviors of aripiprazole and cariprazine at the human D₂ and D₃ receptor are evaluated. A potential correlation between kinetics and in vivo profiles, especially cariprazine’s action on neg. symptoms in schizophrenia, is investigated. The binding kinetics of four ligands were indirectly evaluated. After the receptor preparations were pre-incubated with the unlabeled ligands, the dissociation was initiated with an excess of [³H]spiperone. Slow dissociation kinetics characterizes aripiprazole and cariprazine at the D₂ receptor. At the D₃ receptor, aripiprazole exhibits a slow monophasic dissociation, while cariprazine displays a rapid biphasic behavior. Functional ss-arrestin assays and mol. dynamics simulations at the D₃ receptor confirm a biphasic binding behavior of cariprazine. This may influence its in vivo action, as the partial agonist could react rapidly to variations in the dopamine levels of schizophrenic patients and the ligand will not quant. dissociate from the receptor in one single step. With these findings novel agents may be developed that display rapid, biphasic dissociation from the D₃R to further investigate this effect on in vivo profiles. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Computed Properties of C21H32Cl2N4O).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Computed Properties of C21H32Cl2N4O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis was written by Genaro-Mattos, Thiago C.;Anderson, Allison;Allen, Luke B.;Tallman, Keri A.;Porter, Ned A.;Korade, Zeljka;Mirnics, Karoly. And the article was included in Molecular Psychiatry in 2020.Electric Literature of C21H32Cl2N4O This article mentions the following:

Cariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7⁺/^– and wild-type mouse offspring, and tested the biochem. effects of CAR in human serum samples. Dhcr7^+/- and wild-type time-pregnant mice were exposed to vehicle or 0.2 mg/kg CAR from E12 to E19. Levels of CAR, CAR metabolites, sterols, and oxysterols were measured in the brain of maternally exposed offspring at various time points using LC-MS/MS. Embryonic exposure to CAR significantly increased levels of 7-DHC in all organs of exposed embryos, with a particularly strong effect in the brain. Detectable levels of CAR and elevated 7-DHC were observed in the brain of newborn pups 14 days after drug exposure. In addition, CAR altered sterol metabolism in all animals analyzed, with the strongest effect on the brain of Dhcr7⁺/^– pups born to Dhcr7⁺/^– dams. Furthermore, CAR elevated toxic oxysterols in the brain of maternally exposed Dhcr7⁺/^– offspring to levels approaching those seen in a mouse model of Smith-Lemli-Opitz syndrome. Finally, we observed that patients taking CAR have elevated 7-DHC in their serum. In summary, maternal DHCR7 heterozygosity, combined with offspring DHCR7 heterozygosity might represent a vulnerability factor to medications that interfere with sterol biosynthesis. Due to the conserved sterol biosynthesis between mice and humans, we suggest that the 1-3% of patient population with single-allele DHCR7 mutations might not be ideal candidates for CAR use, especially if they are nursing, pregnant or plan to become pregnant. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Electric Literature of C21H32Cl2N4O).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Electric Literature of C21H32Cl2N4O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study. was written by Earley, Willie;Burgess, Maria Victoria;Rekeda, Ludmyla;Dickinson, Regan;Szatmári, Balázs;Németh, György;McIntyre, Roger S;Sachs, Gary S;Yatham, Lakshmi N. And the article was included in The American journal of psychiatry in 2019.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea This article mentions the following:

OBJECTIVE: Cariprazine, a dopamine D₃/D₂ and 5-HT_1A receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression. METHODS: In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity. RESULTS: Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups. CONCLUSIONS: Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

[The newer antipsychotic cariprazine (reagila): perspectives for use in different stages of schizophrenia therapy]. was written by Ivanov, S V;Voronova, E I. And the article was included in Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova in 2021.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea This article mentions the following:

Cariprazine is a newer 3rd generation antipsychotic acting as partial agonist for dopamine receptors with unique higher affinity for D3 than D2 receptors. This review article summarizes key data from preclinical and clinical studies of cariprazine including pharmacodynamics, pharmacokinetics, clinical efficacy and safety/acceptability in acute short-term and long-term maintenance and relapse prevention therapy in patients with schizophrenia. Efficacy and safety of cariprazine in patients schizophrenia with predominantly negative symptoms resistant to previous antipsychotic therapy is discussed as well. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics