- Synthesis, in vitro cytotoxicity and biological evaluation of twenty novel 1,3-benzenedisulfonyl piperazines as antiplatelet agents
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In order to discover antiplatelet drug with novel structure and expand our research scope, total twenty 1,3-benzenedisulfonyl piperazines, were designed and synthesized. These target compounds were divided into two series, namely 4-methoxy-1,3-benzenedisulfonyl piperazines of series 1 and 4-ethoxy-1,3-benzenedisulfonyl piperazines of series 2. With adenosine diphosphate (ADP), arachidonic acid (AA) and collagen as inducers, respectively, the Born turbidimetric method was used to screen the antiplatelet activity in vitro of all target compounds at a concentration of 1.3 μM, with aspirin and picotamide as positive control drugs. And of which, the activities of five compounds for collagen were higher than both picotamide and aspirin. In ADP or AA channel, compounds with an inhibition rate greater than 33% were selected, and their corresponding IC50 values were obtained. According to the IC50, the in vitro activity of one compound for ADP was higher than picotamide, and for AA, two compounds were higher than two positive control drugs and other two compounds only higher than or equal to aspirin. The preliminary analysis of the structure-activity relationship of the target compounds involved in this study was completed. Further, eight compounds exhibiting higher activity in one or two test channels, were subjected to cytotoxicity test on mouse fibroblasts (L929) by CCK-8 method. The in vitro cytotoxicity of most test compounds showed less than or same to control drug picotamide at 10 μM, but at the higher concentration of 100 μM, merely two compounds exhibited higher cell survival rate than that of picotamide. In addition, compound N1,N3-di(4-ethoxy-1,3-phenylenedisulfonyl)bis(1-(m-tolyl)piperazine), which is delivery activity in the three test channels, and another compound N1,N3–di(4-methoxy-1,3-phenylenedisulfonyl)bis(1-(m-tolyl)piperazine), which has the lowest cytotoxic in vitro compound among series 1 and series 2, respectively, are found and selected for simulation analysis as two most likely to dock with the receptor P2Y12. Each of synthesized compounds in silico molecular property and ADME (absorption, distribution, metabolism and excretion) are predicted by using Molinspiration property engine v2018.10 and PreADMET online servers, respectively. Compared with other series of compounds in the previous stage, the two series compounds obtained after the introduction of piperazinyl have a similar in vitro activity.
- Liu, Xiu-jie,Wang, Yan,Wang, Xiao,Zhang, Zhi-hao
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- PHARMACEUTICAL 6,5 HETEROBICYCLIC RING DERIVATIVES
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The invention relates to 6,5 heterobicyclic ring derivatives, processes for preparing them, pharmaceutical compositions containing them and their use for the treatment of inflammatory conditions driven by STING activation, such as SLE and geographic atrophy.
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Paragraph 0064-0065; 0088-0089
(2019/09/01)
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- Design, synthesis, and biological evaluation of structurally constrained hybrid analogues containing ropinirole moiety as a novel class of potent and selective dopamine D3 receptor ligands
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Two series of hybrid analogues were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine D3 receptor. Binding affinities of target compounds were determined (using the method of radioligand binding assay). Compared to comparator agent BP897, compounds 2a and 2c were found to demonstrate a considerable binding affinity and selectivity for D3 receptor, and especially compound 2h was similarly potent and more selective D3R ligand than BP897, a positive reference. Thus, they may provide valuable information for the discovery and development of highly potent dopamine D3 receptor ligands with outstanding selectivity.
- Zhou, Benhua,Hong, Kwon Ho,Ji, Min,Cai, Jin
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p. 1597 - 1609
(2018/07/31)
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- Pd-Catalyzed Synthesis of Piperazine Scaffolds under Aerobic and Solvent-Free Conditions
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A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures.
- Reilly, Sean W.,Mach, Robert H.
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supporting information
p. 5272 - 5275
(2016/10/31)
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- Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1-phenylpiperazine scaffold
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Previously, we identified 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2- methoxyphenyl)piperazin-1-yl)propan-2-ol (1) as a novel Hsp90 inhibitor with moderate activity through virtual screening. In this study, we report the optimization process of 1. A series of analogues containing the 1-phenylpiperazine core scaffold were synthesized and evaluated. The structure-activity relationships (SAR) for these compounds was also discussed for further molecular design. This effort afforded the most active inhibitor 13f with improved activity in not only target-based level, but also cell-based level compared with the original hit 1.
- Jia, Jian-Min,Liu, Fang,Xu, Xiao-Li,Guo, Xiao-Ke,Jiang, Fen,Cherfaoui, Bahidja,Sun, Hao-Peng,You, Qi-Dong
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supporting information
p. 1557 - 1561
(2014/03/21)
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- Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
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High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11β-HSD1 IC50 = 3 nM).
- Sun, Daqing,Wang, Zhulun,Di, Yongmei,Jaen, Juan C.,Labelle, Marc,Ma, Ji,Miao, Shichang,Sudom, Athena,Tang, Liang,Tomooka, Craig S.,Tu, Hua,Ursu, Stefania,Walker, Nigel,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
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scheme or table
p. 3513 - 3516
(2009/04/11)
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- A general and convenient synthesis of N-aryl piperazines
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A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.
- Liu, Kevin G.,Robichaud, Albert J.
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p. 7921 - 7922
(2007/10/03)
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- Mono N-arylation of piperazine(III): Metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate
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A novel application of Pd0-catalyzed arylation to mono N-arylated piperazines, its mechanism, and its application towards the novel syntheses of the key differentially N,N′-diarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N′-(4-aminophenyl)piperazine 5 as well as posaconazole 1 are described.
- Hepperle, Michael,Eckert, Jeffrey,Gala, Dinesh,Shen, Lan,Anderson Evans,Goodman, Andrew
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p. 3359 - 3363
(2007/10/03)
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- Nickel-catalysed selective N-arylation or N,N′-diarylation of secondary diamines
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The selective synthesis of N-aryl or N,N′-diaryl piperazines and trimethylene(bis)piperidines from the corresponding diamines and aryl chlorides using a catalyst combination of Ni(0) associated to 2,2′-bipyridine is described. The Ni/2,2′-bipyridine catalyst is also effective for the sequential arylation of piperazine. The preparation of novel and unsymmetrical 1,4-diaryl piperazines is reported.
- Brenner, Eric,Schneider, Rapha?l,Fort, Yves
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p. 6913 - 6924
(2007/10/03)
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- Nickel-mediated amination chemistry. Part 2: Selective N-arylation or N,N'-diarylation of piperazine
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The 2,2'-bipyridine liganded Ni catalyst has revealed a good selectivity in the mono arylation of piperazine starting from aryl chlorides allowing a selective and efficient synthesis of N-arylpiperazines using stoichiometric amounts of reagents. The preparation of N,N'-diaryl substituted piperazines is also described. (C) 2000 Elsevier Science Ltd.
- Brenner, Eric,Schneider, Rapha?l,Fort, Yves
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p. 2881 - 2884
(2007/10/03)
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- Process for producing heterocyclic aromatic amine or arylamine
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A heterocyclic aromatic halide or an aryl halide is reacted with an amine compound in the presence of a base to give a heterocyclic aromatic amine or an arylamine, respectively. In this reaction, a catalyst comprising a palladium compound and a tertiary phosphine is used for the preparation of a heterocyclic aromatic amine, and a catalyst comprising a palladium compound and a trialkylphosphine is used for the preparation of an arylamine.
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- Microwave assisted rapid synthesis of 1-arylpiperazines
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1-Arylpiperazines, an important class of compounds were synthesized rapidly under Microwave irradiation from diethanolamine and substituted anilines using Pollard's method of synthesis. The yields obtained were comparable with the conventional yields and drastic reduction in reaction time was observed.
- Jaisinghani, Harsha G.,Chowdhury, Boudhayan Roy,Khadilkar
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p. 1175 - 1178
(2007/10/03)
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- Synthesis of N-arylpiperazines from aryl halides and piperazine under a palladium tri-tert-butylphosphine catalyst
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A Pd/P(t-Bu), catalyst system has revealed very high activity and selectivity for the amination of N-(hetero)aryl halides with unprotected piperazine. A wide variety of N-(hetero)arylpiperazines could be prepared using this catalyst. Turnover numbers up to 6400mol/mol have been obtained.
- Nishiyama, Masakazu,Yamamoto, Toshihide,Koie, Yasuyuki
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p. 617 - 620
(2007/10/03)
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- Synthesis of arylpiperazines via palladium-catalyzed aromatic amination reaction with unprotected piperazines
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A series of arylpiperazines were synthesized in moderate to good yields by palladium-catalyzed coupling reaction of aryl halides with unprotected piperazines. Very high regioselectivities were observed when using 2-methyl or 2,6-dimethylpiperazine.
- Zhao, Shu-Hai,Miller, Aubry K.,Berger, Jacob,Flippin, Lee A.
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p. 4463 - 4466
(2007/10/03)
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- Use of 2-Oxazolidinones As Latent Aziridine Equivalents. III. Preparation of N-Substituted Piperazines.
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A number of N-aryl and N-alkyl substituted piperazines 1 were prepared from variously substituted 2-oxazolidinone derivatives 3.The method involved treatment of 3 with HBr in glacial acetic acid followed by heating the resulting ring-opened salts 5 in alcoholic solvent.The piperazines 1a-1q were isolated by crystallization in yields ranging from 23-91percent.
- Poindexter, Graham S.,Bruce, Marc A.,LeBoulluec, Karen L.,Monkovic, Ivo
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p. 7331 - 7334
(2007/10/02)
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- Antiviral agents
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Antiviral compounds (I): the symbols being as defined in the specification, are efficacious against infections caused by a variety of DNA viruses, RNA viruses and retroviruses. Other specified compounds also exhibit activity. The compounds have a wider spectrum of activity than known antiviral substances.
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- Oxazolopyridine compounds
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Compounds of general formula (I): STR1 in which: R1 and R2 each represent a hydrogen atom or, with the oxygen and nitrogen, form an --O--CO--N-- linkage, W represents a halogen atom or a lower alkyl or alkoxy group optionally substituted with one or more halogen atoms, such as trifluoromethyl, and m being between 0 and 3, A represents a linear or branched lower alkylene group, and Ar represents an aryl or heteroaryl group optionally substituted with one or more halogen atoms or with one or more lower alkyl, hydroxy, hydroxysulfonyloxy, lower alkoxy or aryloxy groups optionally substituted with one or more halogen atoms, such as a trifluoromethyl group, on the understanding that lower alkyl or lower alkyloxy radical is understood to mean a linear or branched alkyl group comprising from 1 to 6 carbon atom, their isomers, epimers and diastereoisomers. Medicinal products useful in the treatment of pain.
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- ISOINDOLINYL-ALKYL-PIPERAZINES
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The invention is generally concerned with isoindolinyl-alkylpiperazine compounds generally characterized by the formula STR1 wherein X is halogen or trifluoromethyl; n is an integer ranging from 2 to 5; Y is STR2 in which R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano; R 2 is hydrogen, halogen, lower alkyl, lower alkoxy; and R 3 is hydrogen, cyano. These compounds are useful as diuretic and/or antihypertensive agents.
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- Synthesis and Insecticidal Activity of N4-Aryl-N1-(O,O-dialkyl thiophosphoryl)Piperazines
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Eleven new N4-aryl-N1-(O,O-dialkyl thiophosphoryl) piperazines have been synthesised as possible insecticides by the condensation of N-aryl piperazines with O,O-dialkyl chloro-tiophosphates and tested against Periplanata americana.
- Agarwal, Kamlesh C.
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p. 1170 - 1171
(2007/10/02)
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