119532-26-2Relevant articles and documents
Synthesis method of cariprazine key intermediate 1-(2,3-dichlorophenyl)piperazine hydrochloride
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Paragraph 0042-0044; 0051-0056, (2021/11/26)
The invention discloses a synthesis method of a cariprazine key intermediate 1-(2,3-dichlorophenyl)piperazine hydrochloride, and belongs to the field of medicine synthesis. The method comprises the following steps: (1) taking a compound 1 and a compound a as raw materials, and conducting reacting to obtain a compound 2; (2) carrying out nitro reduction reaction by taking the compound 2 and a reducing agent as raw materials to obtain a compound 3; and (3) taking the compound 3 as a raw material, and carrying out diazotization reaction and deprotection reaction to obtain the 1-(2,3-dichlorophenyl)piperazine hydrochloride. The raw materials used in the synthesis method are low in toxicity, low in cost and easy to obtain, no noble metal catalyst or phosphorus ligand is used, the equipment requirement is simple, the product yield is high, the purity is high, and the synthesis method is suitable for large-scale industrial production and has a good application prospect.
Compound with dopamine D3 receptor adjusting activity, and applications thereof
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Paragraph 0191-0194, (2019/03/22)
The invention relates to a compound with dopamine D3 receptor adjusting activity, and applications thereof, and more specifically discloses dopamine receptor D3R as a novel target of post-traumatic stress disorder (PTSD) in prevention, treatment/or auxiliary treatment of PTSD, and screening of anti-PTSD medicines, and relates to applications of a compound with dopamine receptor D3R adjusting activity in preparation of medicines used for preventing, treatment and/or auxiliary treatment of PTSD.
Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D3 receptor agonists
Cao, Yongkai,Sun, Ningning,Zhang, Jiumei,Liu, Zhiguo,Tang, Yi-zhe,Wu, Zhengzhi,Kim, Kyeong-Man,Cheon, Seung Hoon
supporting information, p. 1457 - 1465 (2018/10/02)
The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathways and the sequence similarity between D2R and D3R have rendered the development of D3R-selective ligands challenging. Herein, we designed and synthesized a series of piperazine-phthalimide bitopic ligands based on a fragment-based and molecular docking inspired design. Compound 9i was identified as the most selective D3R ligand among these bitopic ligands. Its selectivity was improved compared to reference compounds 1 and 2 by 9- and 2-fold, respectively, and it was 21-fold more potent than compound 2. Molecular docking demonstrated that the orientation of Leu2.64 and Phe7.39 and the packing at the junction of helices may affect the specificity for D3R over D2R. Functional evaluation revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity at D3R with a 199-fold increase in potency compared to quinpirole. These results may be useful for the fragment-based design of bitopic compounds as selective D3R ligands.