- Preparation method of flibaserin hydrochloride
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The invention relates to the technical field of synthesis of medical intermediates, particularly to a preparation method of flibaserin hydrochloride. According to the preparation method, o-phenylenediamine and 3-trifluoromethylphenylpyrazine are used as raw materials; o-phenylenediamine reacts with ethyl acetoacetate to obtain a compound 10-1-G; the 3-trifluoromethylphenylpyrazine compound I is subjected to a two-step substitution reaction to obtain a compound 10-1-B; and the compound 10-1-B and the compound 10-1-G are subjected to a substitution reaction to obtain a final product compound flibaserin hydrochloride. The invention aims to reduce the cost, optimize the process and facilitate industrial production. The method is simple and convenient to operate, reasonable in reaction process,low in production cost, good in product quality, free of environmental pollution and suitable for industrial production, wherein the content of the product is higher than 99.5%.
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- A new method for synthesizing flibanserin (by machine translation)
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The invention relates to a new method for synthesizing of flibanserin, which belongs to the technical field of organic synthesis. The invention respectively in order to triethanolamine and between amino benzotrifluoride as the starting material, to prepare the piperazine intermediate; then to the O-phenylene diamine and the original four carbonate as raw material, the preparation of the ethoxy and imidazole intermediate; the obtained piperazine intermediate and benzimidazole intermediate undergo the substitution reaction, and hydrochloric acid deprotection to obtain the target product of flibanserin. The invention has few synthetic steps, few by-products, intermediate products and the target product yield is relatively high, intermediate product 2 - ethoxy and imidazole yield up 94.2%, the target product yield can reach 56.2%, it can be seen, the invention overcomes the substance in the prior art synthesis step is tedious, and more byproducts, target low yield of product defect. In addition, the present invention has a simple structure, high purity of product, the economic and environmental protection industrial line, has a very wide range of use and potential economic benefits. (by machine translation)
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Paragraph 0052; 0060; 0061; 0070; 0076; 0077; 0081; 0087
(2019/02/04)
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- Benzo-aza-alkyl aryl piperazine derivative and applications in preparation of drugs
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The invention discloses a benzo-aza-alkyl aryl piperazine derivative and applications in preparation of drugs. The derivative shows the effect on central nervous systems, especially on the double highaffinity activity of a 5-HT acceptor and a Sigma-1 acceptor. Various physiological and pharmacological effects are brought into play in the body; and the compound can be used as a pharmaceuticalactive substance, especially used for anti-depression, anti-anxiety, anti-bipolar affective disorder and anti-neuropathic pain, and can also be used as an intermediate to prepare other pharmaceuticalactive compounds. The compound is fast in effect and small in toxic and side effect, and can meet demands of clinical applications; and the compound is a compound or a free base or salt thereof havingthe following structural formula (IV). The structure of the compound or the free base or salt thereof is shown as the structural formula (IV).
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Paragraph 0193-0196
(2019/02/10)
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- The preparation method of the flibanserin
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The invention discloses a preparation method of flibanserin. The preparation method uses trifluoromethylbenzene, triamine (2-halogen ethyl) and ortho-nitroaniline which are easy to obtain as raw materials and adopts classical elementary reactions such as cyclization, substitution, reduction and condensation, so that the flibanserin is prepared. The raw materials of the preparation method are easy to obtain, the technology is succinct, the yield is high, the preparation method is economical and environment-friendly, and a new preparation way is provided for the industrial production of the flibanserin.
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Paragraph 0033; 0034
(2017/08/24)
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- Preparation method of flibaserin intermediate
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The invention discloses a method belonging to the field of heterocyclic compounds, and concretely relates to a preparation method of a flibaserin intermediate. The preparation method comprises the following steps of (1) dissolving 1-(3-trifluoromethylphenyl) piperazine hydrochloride in a solvent a, and reacting with 2-halogenated ethanol or ethylene oxide in the presence of alkali to obtain 2-(4-(3-trifluoromethylphenyl) piperazine-1-ethanol; (2) reacting the 2-(4-(3-trifluoromethylphenyl) piperazine-1-ethanol with a chloride agent compound to obtain a compound as shown in a formula I. According to the preparation method, the reaction selectivity is improved, the generation of impurities is reduced, the product purity is improved, and the preparation method is simple and convenient to operate, environmentally-friendly, and beneficial for industrialized mass production.
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Paragraph 0036; 0037; 0038; 0039; 0040; 0041; 0042-0044
(2017/07/19)
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- HETEROARYLTHIO COMPOUNDS
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Heteroarylthio compounds covalently linked to an arylpiperazine moiety for the treatment of neurological conditions.
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Page/Page column 36
(2012/05/04)
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- TREATMENT OF ORGANOPHOSPHATE EXPOSURE WITH TETRAHYDROINDOLONE ARYLPIPERAZINE COMPOUNDS
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A method of treating exposure to organophosphate agents through the use of compounds comprising tetrahydroindolone and arylpiperazine moieties.
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- 2-[(3-Methoxyphenylethyl)phenoxy]-based ABCB1 inhibitors: Effect of different basic side-chains on their biological properties
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Recently, 2-[(3-methoxyphenylethyl)phenoxy]-moiety has been selected for the design and synthesis of new small ABCB1 inhibitors. In the present paper, this moiety has been linked through a spacer of 2-5 carbon atoms to the nitrogen of three different basic nuclei such as: (i) N-4-arylpiperazine, (ii) N-4-methylpiperazine, and (iii) 6,7-dimethoxytetrahydroisoquinoline. The results demonstrated that all the selected basic nuclei were well tolerated and that, globally, the best inhibitory activity for each series was obtained when the spacer between the 2-[(3-methoxyphenylethyl)phenoxy] moiety and the basic nucleus consisted of a four-carbon chain. Among the synthesized compounds, N-4-methylpiperazine- 10c (IC50 = 0-15 μM) and tetrahydroisoquinoline-derivatives 11c (IC50 = 0.08 μM) with the spacer n = 4 for both series, displayed the best potency to inhibit ABCB1 activity. Moreover, for each compound, the ABCB1 interacting mechanism has been evaluated by three combined biological assays. N-4-methylpiperazine- (10a-d) and tetrahydroisoquinoline- (11a-d) derivatives were Cyclosporin A-like ABCB1 nontransported substrates.
- Colabufo, Nicola Antonio,Berardi, Francesco,Perrone, Roberto,Rapposelli, Simona,Digiacomo, Maria,Vanni, Michael,Balsamo, Aldo
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supporting information; experimental part
p. 7602 - 7613
(2009/11/30)
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- Composition and method for treating emesis
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Methods for treating emesis using compositions comprising a bicyclic ring moiety covalently linked to a substituted arylpiperazine moiety are disclosed.
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Page/Page column 8
(2010/02/11)
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- Microwave-assisted solvent-free synthesis of 3-[(4-substituted piperazin-1-yl)alkyl] imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones as serotonin3 (5-HT3) receptor antagonists
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A series of novel 3-[(4-substituted piperazin-1-yl)alkyl]imidazo[2,1-b][1, 3]benzothiazol-2(3H)-ones were prepared by microwave irradiation using alumina as solid support and also by a conventional method. The compounds were characterized by spectral data and the purity was ascertained by microanalysis. The synthesized compounds were evaluated for 5-hydroxytryptamine3 antagonisms in a longitudinal muscle-myenteric plexus preparation from guinea pig ileum against the 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine. Among the test compounds, 3-[2-(4-methylpiperazin- 1-yl)ethyl]imidazo[2,1-6][1,3]benzothiazol-2(3H)-one (3b) showed most favorable 5-hydroxytryptamine3 antagonism (pA2 6.7) in the isolated guinea pig ileum.
- Mahesh,Venkatesha Perumal,Pandi
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p. 411 - 414
(2007/10/03)
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- Tetrahydroindolone and purine derivatives linked to arylpiperazines
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Pharmaceutical composite compositions comprising tetrahydroindolones linked to arylpiperazines and derivatives thereof are disclosed. Specifically, composite compositions useful in treating anti-psychotic disorders are disclosed. The composite compositions disclosed herein can effectively ameliorate symptoms and treat psychotic disorders without causing a decrease in cognitive function. Generally, the composite compounds consist of two moieties, moiety A and B in which a tetrahydroindolone comprises a moiety A linked through a linker L to a moiety B, where B is an arylpiperazinyl moiety. The composite compound provides anti-psychotic actively by interaction with GABA, seratoninne and dopamine receptors. The composite molecules with the combined activities will provide treat psychiatric and neurological diseases without cognitive impairment.
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- TETRAHYDROINDOLONE AND PURINE DERIVATIVES LINKED TO ARYLPIPERAZINES
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Pharmaceutical composite compositions comprising tetrahydroindolones linked to arylpiperazines and derivatives thereof are disclosed. Specifically, composite compositions useful in treating anti-psychotic disorders are disclosed. The composite compositions disclosed herein can effectively ameliorate symptoms and treat psychotic disorders without causing a decrease in cognitive function. Generally, the composite compounds consist of two moieties, moiety A and B in which a tetrahydroindolone comprises a moiety A linked through a linker L to a moiety B, where B is an arylpiperazinyl moiety. The composite compound provides anti-psychotic actively by interaction with GABA, seratoninne and dopamine receptors. The composite molecules with the combined activities will provide treat psychiatric and neurological diseases without cognitive impairment.
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- Substitute pyrimidine compounds and the use thereof
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The present invention relates to the use of pyrimidine compounds of the following formula: wherein R1, R2, R3, A, B and Ar have the meanings indicated in the description. The compounds according to the invention have a high affinity for the dopamine D3receptor and can therefore be used to treat disorders which respond to dopamine D3ligands.
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- Synthesis of new 1,2,3-benzotriazin-4-one-arylpiperazine derivatives as 5-HT(1A) serotonin receptor ligands
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A series of novel 1,2,3-benzotriazin-4-one derivatives was prepared and evaluated as ligands for 5-HT receptors. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT(1A) receptor, some of which were selective with respect 5-HT(2A) and 5-HT(2C) receptors. Six analogues (1a, 2a, 2b, 2c, 2e and 2i) were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and α1-, α2-adrenergic receptors. A o-OCH3 derivative (2e) bound at 5-HT(1A) sites with subnanomolar affinity (IC50=0.059 nM) and shows high selectivity over all considered receptors and may offer a new lead for the development of therapeutically efficacious agents. Copyright (C) 2000 Elsevier Science Ltd.
- Caliendo, Giuseppe,Fiorino, Ferdinando,Grieco, Paolo,Perissutti, Elisa,Santagada, Vincenzo,Severino, Beatrice,Bruni, Giancarlo,Romeo, Maria Rosaria
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p. 533 - 538
(2007/10/03)
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