- Substituted indole compound and method and use thereof
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The invention provides a new indole compound, pharmaceutically acceptable salts and medicinal preparations thereof, and a use of the new indole compound in selective inhibition of 5-hydroxytryptamine reuptake and /or excitation of a 5-HT1A receptor. The invention also relates to medicinal compositions comprising the compounds, and a method for treating the central nervous system dysfunction of mammals, especially humans by using the medicinal compositions.
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Paragraph 0310; 0327; 0328
(2018/11/03)
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- Chrysin-piperazine conjugates as antioxidant and anticancer agents
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Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH+ and ABTS++, particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.
- Patel, Rahul V.,Mistry, Bhupendra,Syed, Riyaz,Rathi, Anuj K.,Lee, Yoo-Jung,Sung, Jung-Suk,Shinf, Han-Seung,Keum, Young-Soo
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p. 166 - 177
(2016/05/24)
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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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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 50; 51
(2011/04/14)
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- Discovery of a novel 5-HT3 antagonist/5-HT1A agonist 3-amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl} quinazolin-4(3 H)-one (TZB-30878) as an orally bioavailable agent for irritable bowel syndrome
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We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT 3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315 -1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT 1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT 1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.
- Asagarasu, Akira,Matsui, Teruaki,Hayashi, Hiroyuki,Tamaoki, Satoru,Yamauchi, Yukinao,Minato, Kouichi,Sato, Michitaka
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experimental part
p. 7549 - 7563
(2010/12/30)
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- TRIAZOLE DERIVATIVES HAVING ANTIFUNGAL ACTIVITY, METHOD FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A triazole derivative of formula 1 or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof is superior to the conventional antifungal drugs in antifungal activity against a wide spectrum of pathogenic fungi, and has advantageously low toxicity.
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Page/Page column 43
(2009/01/24)
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- ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS
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The present invention provides Stearoyl CoA Desaturase (SCD) inhibitors, hi particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase 1 (SCD 1) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase (SCD) inhibitors.
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Page/Page column 50
(2008/12/05)
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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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- FACTOR XA COMPOUNDS
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The present invention is directed to novel compounds of Formula (I) and forms and pharmaceutical compositions thereof, and the use thereof as inhibitors of Factor Xa.
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Page/Page column 37-38
(2008/06/13)
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- Oligomeric aminodiol-containing compounds, libraries thereof, and process of preparing the same
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Oligomeric compounds comprising a plurality of aminodiol monomer subunits joined by linking groups are provided, as well as libraries of such compounds and processes for preparing the oligomeric compounds and libraries.
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- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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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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- Benzenesulfonamide derivatives and their use as MEK inhibitors
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Benzenesulfonamides of formula (I), in which W is OR1, NR2OR1, NRARB, NR2NRARB, or NR2(CH2)2-4NRARBand the other variables as defined in the claims, are inhibitors of MEK and are effective in the treatment of proliferative diseases, cancer, stroke, heart failure, xenograft rejection, arthritis, cystic fibrosis, hepatomegaly, cardiomegaly, Alzheimer's disease, complications of diabetes, septic shock, and viral infection.
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- Fused heterocyclic compounds and pharmaceutical applications thereof
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The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism. The inventive compound is expected to make a highly safe antipsychotic agent associated with less side effects, such as extrapyramidal symptoms and endocrine disturbance, which are observed when a conventional antipsychotic agent having a D2receptor blocking action is administered. Therefore, the inventive compound can be used as a therapeutic agent for the diseases such as schizophrenia.
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- D4 receptor selectivity piperazine derivatives
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Piperazine derivatives of the formula I in which R1and R2have the meanings given in claim1are dopamine ligands with a selectivity for the D4 receptor and are suitable for the treatment and prophylaxis of states of anxiety, depression, schizophrenia, obsessions, Parkinson's disease, tardive dyskinesia, nausea and disorders of the gastro-intestinal tract.
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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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- Nickel-catalysed couplings of aryl chlorides with secondary amines and piperazines
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The reaction of aryl chlorides with secondary amines or piperazines in the presence of an in situ generated liganded nickel catalyst gives arylamines in good yields. Our process provides a mild, convenient and cheap method of arylamination starting from readily available substrates.
- Brenner, Eric,Schneider, Raphael,Fort, Yves
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p. 12829 - 12842
(2007/10/03)
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- Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl- containing thiazolidinediones
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A series of substituted pyridyl- and quinolinyl-containing 2,4- thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPARγ by 5a/5a maleate did not show any significant transactivation of PPARα or PPARγ.
- Lohray,Bhushan, Vidya,Reddy, A. Sekar,Rao, P. Bheema,Reddy, N. Jaipal,Harikishore,Haritha,Vikramadityan, Reeba K.,Chakrabarti, Ranjan,Rajagopalan,Katneni
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p. 2569 - 2581
(2007/10/03)
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- Marcfortine/paraherquamide derivatives useful as antiparasitic agents
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There are disclosed 18-thiomarcfortine derivatives of the natural products marcfortine A, B and C, C-18 thioparaherquamide and derivatives thereof, novel N-1 marcfortines A, B, and C and derivatives thereof, novel N-1 paraherquamide and derivatives thereof usefull in the treatment and prevention of helninth and arthropod infections of animals and plants. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Examiner Robert T. Bond whose telephone number is (703)308-4711. The examiner can normally be reached on Monday through Friday from 8:00 AM to 4:30 PM.
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- (1-BENZODIOXIN-6-YLMETHYL)-4-SUBSTITUTED PIPERAZINES HAVING ANTIPSYCHOTIC ACTIVITY
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Benzodioxine compounds of the formula: STR1 in which Het is a five-or six-membered heterocyclic radical containing from one to three hetero atoms, and from one to three double bonds, optionally substituted by one or more alkyl or alkoxy radicals each from C 1 to C 5. These compounds and physiologically tolerable acid addition salts thereof may be used as medicines, especially in the treatment of psychoses.
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