- A New and Practical Synthesis of Cariprazine through the Facile Construction of 2-[ trans -4-(3,3-Dimethylureido)cyclohexyl]acetic Acid
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A new, practical, and improved synthetic route to cariprazine is described. The key step is the facile preparation of 2-[4-(3,3-dimethylureido)cyclohexyl]acetic acid in the trans configuration through direct recrystallization. The entire synthetic procedure was accomplished under mild conditions while avoiding tedious purification processes. The trans configuration of cariprazine was confirmed by X-ray crystallographic analysis.
- Chen, Xiaowen,Ni, Feng,Liu, Yu,Fu, Lei,Li, Jianqi
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- Preparation method of carlyrazide and intermediate compound
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The present invention provides a method for preparing carlirazine and an intermediate compound. The preparation method of the present invention is simple, no need for high temperature and high pressure conditions and the use of a precious catalyst, cost savings, and the yield and purity of carilazine are high.
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Paragraph 0174-0185
(2022/03/27)
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- Nitrogen-containing ring derivative regulator as well as preparation method and application thereof
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The invention relates to a nitrogen-containing ring derivative regulator as well as a preparation method and an application thereof. In particular, the present invention relates to a compound represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the compound, and an application of the compound as a G-protein coupled receptor modulator in the treatment or prevention of central nervous system diseases and/or mental diseases.
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- D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine
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Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-bi
- Shen, Yudao,McCorvy, John D.,Martini, Michael L.,Rodriguiz, Ramona M.,Pogorelov, Vladimir M.,Ward, Karen M.,Wetsel, William C.,Liu, Jing,Roth, Bryan L.,Jin, Jian
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p. 4755 - 4771
(2019/05/08)
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- Method for preparing medicinal carliflazine composition
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The invention provides a medicinal high-purity carliflazine composition and a method for preparing the medicinal high-purity carliflazine composition. The preparation process of the medicinal carliprazine composition can obviously reduce the content of mo
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- Preparation method of cariprazine
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The invention discloses a preparation method of cariprazine (Cariprazine, RGH 188). The method includes the preparation steps of preparing 4-[2-[4-(2,3-dichlorophenyl)piperazine]-1-based]ethyl]cyclohexanone by making 4-(2-hydroxyethyl)cyclohexanone and 1-(2,3-dichlorophenyl)piperazine subjected to a condensation reaction, preparing trans-4-[[2-]4-(2,3-dichlorophenyl)piperazine]-1-based]ethyl]cyclohexylamine by making the obtained intermediate subjected to a reduction ammonolysis reaction, and preparing cariprazine by making the intermediate and N,N-dimethylcarbamyl chloride subjected to an acylation reaction. According to the preparation method, raw materials can be easily obtained, the process is simple, and the method is economical, environmentally friendly and suitable for industrialized production.
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Paragraph 0033-0034
(2017/01/19)
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- 1,4-CYCLOHEXYLAMINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
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The invention relates to a process for the synthesis of Cariprazine, an antipsychotic compound useful in the treatment of positive and negative symptoms associated to schizophrenia, with the following structural formula: (A) The invention further relates to the synthesis of intermediates useful in the preparation of Cariprazine.
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- A structure-activity analysis of biased agonism at the dopamine D2 receptor
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Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin- 2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.
- Shonberg, Jeremy,Herenbrink, Carmen Klein,López, Laura,Christopoulos, Arthur,Scammells, Peter J.,Capuano, Ben,Lane, J. Robert
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p. 9199 - 9221
(2014/01/06)
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- Discovery of cariprazine (RGH-188): A novel antipsychotic acting on dopamine D3/D2 receptors
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Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D3/D 2 compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D3/
- ágai-Csongor, éva,Domány, Gy?rgy,Nógrádi, Katalin,Galambos, János,Vágó, István,Keser, Gy?rgy Miklós,Greiner, István,Laszlovszky, István,Gere, Anikó,Schmidt, éva,Kiss, Béla,Vastag, Mónika,Tihanyi, Károly,Sághy, Katalin,Laszy, Judit,Gyertyán, István,Zájer-Balázs, Mária,Gémesi, Larisza,Kapás, Margit,Szombathelyi, Zsolt
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p. 3437 - 3440
(2012/06/29)
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- Novel cyclohexyl amides as potent and selective D3 dopamine receptor ligands
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The dopamine D3 receptor is an attractive target for the treatment of schizophrenia. We identified PD137557 (V) as a ligand for the D2 receptor and desired to prepare a selective D3 compound. SAR studies involving different amides and different phenyl piperazines have led to the discovery of 8a and 8c as selective D3 receptor ligands.
- Belliotti, Thomas R.,Kesten, Suzanne R.,Rubin, John R.,Wustrow, David J.,Georgic, Lynn M.,Zoski, Kim T.,Akunne, Hyacinth C.,Wise, Lawrence D.
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p. 2403 - 2408
(2007/10/03)
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