78069-54-2Relevant articles and documents
An improved synthesis of the 5-HT1A receptor agonist Eptapirone free base
Peng, Wei,Chen, Jian,Liu, Hui,Li, Xiufang,Deng, Zhiwei,Yuan, Jing,Peng, Yizhou,Yang, Yanjing,Zhong, Shian
, p. 1321 - 1331 (2019/05/06)
Eptapirone free base, F11440,4-methyl-2-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-1,2,4-triazine-3,5(2H,4H)-dione, represents a potent and selective 5-HT1A receptor agonist with high efficacy and the potential to regulate anxiety disorders. Herein, we report a method to retro-synthesize eptapirone free base. The compound consists of heterocyclic aromatic portion and aliphatic portion, and the synthetic route consisted of a total of nine steps with an overall yield of 8.8% starting from the commercially available materials. The key steps in the synthetic method involved: (1) using sodium hydroxide and ethylene glycol as solvent resulted in a better cyclization and yield (61.6%) of 1,2,4-triazine-3,5(2H,4H)-dione; (2) an acceptable yield (63.1%) of 4-tert-butyl(pyrimidin-2-yl)piperazine-1-carboxylate was obtained under an optimized conditions of using triethylamine as a base, ethanol as a solvent, and a reaction temperature of 50?°C for 16?h with non-metal catalysis and less byproducts; (3) the reaction step of eptapirone could get a better yield (49.6%) with an optimized condition of potassium carbonate as a base, acetonitrile as a solvent, NaI as a catalyst, and a reaction temperature of 50?°C for 12?h by nucleophilic substitution reaction. The main advantages of this route were an acceptable product purity, the commercial availability of all starting materials and the absence of high temperature, high pressure and noble metal catalysts, which could result in more feasible commercial applications.
Full synthesis method of eptapirone
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Paragraph 0089; 0126; 0127; 0128; 0137, (2018/09/12)
The invention discloses a full synthesis method of eptapirone. The full synthesis method comprises the following steps: (1) taking aminourea hydrochloride and trichloracetic aldehyde as raw materialsand carrying out a series of reaction to obtain 2-[2-(aminocarbonyl)hydrazono](CD-1); (2) synthesizing 6-azauracil(CD-2) by the 2-[2-(aminocarbonyl)hydrazono] under the action of sodium hydroxide; (3)taking the 6-azauracil and acetic anhydride to react to obtain 2-acetyl-2H-[1,2,4]triazine-3,5(2H,4H)-diketone(CD3); (4) taking the 2-acetyl-2H-[1,2,4]triazine-3,5(2H,4H)-diketone to react to obtain3-methyl-6-azauracil(CD-4); (5) taking the 3-methyl-6-azauracil to react to obtain 2-(4-chlorobutyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-diketone(CD-5); (6) taking 2-bromopyrimidine, 1-Boc-piperazine and triethylamine to react to obtain 4-(pyrimidine-2-yl)piperazine-1-tert-butyl formate(CD-6); furthermore, reacting to obtain 2-(1-piperazinyl)pyrimidine hydrochloride (1 to 1)(CD-7); (7) taking the 2-(4-chlorobutyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-diketone in step (5) to react with the 2-(1-piperazinyl)pyrimidine hydrochloride in step (6) to obtain the eptapirone(CD-8). The product disclosed by the invention is high in purity and yield and is suitable for industrialized production.
Design, synthesis and biological evaluation of N,N-3-phenyl-3-benzylaminopropanamide derivatives as novel cholesteryl ester transfer protein inhibitor
Zhao, Dongmei,Xie, Honglei,Bai, Changlin,Liu, Chunchi,Hao, Chenzhou,Zhao, Shizhen,Yuan, Hongli,Luo, Changqun,Wang, Jian,Lin, Bin,Zheng, Jiang,Cheng, Maosheng
, p. 1589 - 1597 (2016/04/05)
A series of N,N-3-phenyl-3-benzylaminopropanamide derivatives were identified as novel CETP (cholesteryl ester transfer protein) inhibitors. In our previous study, lead compound L10 was discovered by pharmacophore-based virtual screening (Dong-Mei Zhao et al., 2014). Based on L10 (IC50 8.06 μM), compound HL6 (IC50 10.7 μM) was discovered following systematic structure variation and biological tests. Further optimization of the structure-activity relationship (SAR) resulted in N,N-3-phenyl-3-benzylaminopro panamides derivatives as novel CETP inhibitors. They were synthesized and evaluated against CETP by BODIPY-CE fluorescence assay. Among them, HL16 (IC50 0.69 μM) was a highly potent CETP inhibitor in vitro. In addition, HL16 exhibited favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. The molecular docking of HL16 into the CETP was performed. The binding mode demonstrated that HL16 occupied the CETP binding site and formed interactions with the key amino acid residues.
Exploration of substituted arylpiperazine–tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors
Paudel, Suresh,Acharya, Srijan,Yoon, Goo,Kim, Kyeong-Man,Cheon, Seung Hoon
, p. 5546 - 5555 (2016/10/22)
In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers. Interestingly, six compounds, 9b, 9c, 9d, 9o, 9q and 9u displayed more effective activity than the standard drug, bupropion. The provided SAR data and potent biological activity can offer useful guidelines for designing dual norepinephrine and dopamine reuptake inhibitors as effective therapeutic agents for treatment of several central nervous system diseases.
THERAPEUTIC COMPOUNDS AND COMPOSITIONS
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Page/Page column 27, (2011/01/05)
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
