- Synthesis, 5-HT(1A) and 5-HT(2A) receptor affinity of new 1-phenylpiperazinylpropyl derivatives of purine-2,6- and pyrrolidine-2,5-diones
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Two series of 1-phenylpiperazinylpropyl derivatives 10, 11, 16, 17 and 19-24, structurally related to previously described 5-HT(1A) or 5-HT(2A) ligands 4 and 1, respectively, were synthesized and their binding properties were determined. Structural modifi
- Pawlowski, Maciej,Chlon, Grazyna,Obniska, Jolanta,Zejc, Alfred,Charakchieva-Minol, Sijka,Mokrosz, Maria J.
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- Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma
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Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5–7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.
- Ali, Wesam,Battistelli, Cecilia,D?browska, Monika,Handzlik, Jadwiga,Honkisz-Orzechowska, Ewelina,Jacob, Claus,Kincses, Annamária,Latacz, Gniewomir,Nové, Márta,Rasile, Manuela Monica,Romanelli, Annalisa,Spengler, Gabriella,Starek, Ma?gorzata,Szymańska, Ewa,Zwergel, Clemens
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supporting information
(2020/06/05)
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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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- Indoline-2-ketone D3 receptor ligand and preparation method and application thereof
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The invention discloses an indoline-2-ketone D3 receptor ligand, which is a compound as shown in the formula I or pharmaceutical salt thereof, wherein n=2 or 3; R represents H, 4-CH3, 2,3-diCH3, 2-CH3, 4-OCF3, 3-OCH3, 3,4-diCH3 or 4-Cl. In comparison with the prior art, the compound has a strong activity to a dopamine D3 receptor, is used in treating or preventing central nervous and metal diseases such as schizophrenia, Parkinson's disease, drug dependence and relapse, etc., can be used in neuroprotection, and is used as a tool drug for researching D3 receptor structure, function and diseases related to D3 receptor dysfunction.
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Paragraph 0044; 0051; 0052
(2016/10/08)
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- Hexahydropyrazine-quinoline D3 receptor ligand and preparation method and use
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The present invention discloses a hexahydropyrazino-quinoline D3 receptor ligand, which is a compound shown as formula I or a pharmaceutically acceptable salt thereof, wherein n = 2,3 or 4; R is H, 4-Cl, 2,3-diCl, 4-CH3, 2,3-diCH3, 4-OCF3, 4-OCH3, 2-OCF3, 2,6-di CH3, 3,4-di CH3, 3-CF3, 4-Cl, 3-OCH3, 2-C2H5 or 2-CH3. Compared with the prior art, the compound has strong activity to a dopamine D3 receptor, and can be used for effective treatment of Parkinson's disease, schizophrenia, drug dependence and other central nervous and mental diseases.
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Paragraph 0054
(2016/10/08)
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- Design, synthesis, and biological evaluation of arylpiperazine-benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities
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The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitors necessitate the development of safer and more effective therapeutic agents. Based on the structures of 4-benzylpiperidine carboxamides and trazodone, arylpiperazine-benzylpiperidines with chemical scaffolds different from those of marketed drugs were designed, synthesized, and evaluated for their neurotransmitter reuptake inhibitory activities. The majority of the synthesized compounds showed greater NE than 5-HT reuptake inhibition. The activities were even greater than those of the standard drug, venlafaxine hydrochloride were. The derivatives with a three-carbon linker showed better activities than the derivatives with a two-carbon linker. Among the newly synthesized compounds, 2d exhibited the strongest reuptake inhibition of the neurotransmitters (IC50 = 0.38 μM for NE and 1.18 μM for 5-HT). The biological activity data demonstrate that arylpiperazine-benzylpiperidines have the potential to be developed as a new class of therapeutic agents to treat neuropsychiatric and neurodegenerative disorders.
- Paudel, Suresh,Acharya, Srijan,Kim, Kyeong-Man,Cheon, Seung Hoon
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p. 2137 - 2145
(2016/04/20)
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- Process for preparing selected regioisomer of piperazinylalkyltriazole
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The present invention refers to relates to manufacturing method for the alkyl tree which it will keep Oh it will doze piperidinyl, piperidinyl 1, 3-dipole [...] derivatives and acetylene derivatives the alkyl tree which it will keep Oh it will doze piperi
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Paragraph 0640-0642
(2016/10/10)
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- Synthesis, characterization, and anticancer studies of S and N alkyl piperazine-substituted positional isomers of 1,2,4-triazole derivatives
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A series of 3-[3-[4-(substituted)-1-cyclicamine] propyl]thio-5- substituted[1,2,4]triazoles (8a-m) and 2-[3-[4-(substituted)-1-cyclicamine] propyl]-5-(substituted)-2,4-dihydro-3H[1,2,4]triazole-3-thiones (9a-h) were synthesized with good yields starting from corresponding carboxylic acids using two different methods. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Six compounds had shown good anticancer activity. The triazole derivatives, 9d, 8j, and 8i were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinant of their biological activity. Springer Science+Business Media 2013.
- Murty,Ram, Kesur R.,Rao, B. Ramalingeswara,Rao, Rayudu Venkateswara,Katiki, Mohana Rao,Rao, Janapala Venkateswara,Pamanji,Velatooru
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p. 1661 - 1671
(2014/05/06)
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- Synthesis of new S-alkylated-3-mercapto-1,2,4-triazole derivatives bearing cyclic amine moiety as potent anticancer agents
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A series of 3-[3-[4-(Substituted)-1-cyclicamine]propyl]thio-5- substituted[1,2,4]triazoles (8a-j) were synthesized with good yields starting from corresponding carboxylic acids. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Three compounds had shown good anticancer activity. The triazole derivatives, 8i and 8j were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinants of their biological activity.
- Murty,Ram, Kesur R.,Rao, Rayudu Venkateswara,Yadav,Rao, Janapala Venkateswara,Pamanji,Velatooru
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experimental part
p. 276 - 281
(2012/06/18)
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- Synthesis and preliminary evaluation activity studies of novel 4-(aryl/heteroaryl-2-ylmethyl)-6-phenyl-2-[3-(4-substitutedpiperazine-1-yl) propyl]pyridazin-3(2H)-one derivatives as anticancer agents
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A series of new 4-(aryl/heteroaryl-2-ylmethyl)- 6-phenyl-2-[3-(4- substituted piperazine-1-yl)propyl] pyridazin- 3(2H)-one derivatives were synthesized. The structures of the compounds were confirmed by IR, 1H NMR, and mass spectral data. All the compounds were evaluated for their cytotoxicity toward five human cancer cell lines of different origins viz; HeLa (Cervical), SKBR3 (Breast), HCT116 (Colon), A375 (Skin) & H1299 (Lung) at different concentrations and the IC50 values were determined. HCT116 and HeLa are the most sensitive against the compounds studied. One of them displayed moderate cytotoxicity against SKBR3. Majority of the compounds exhibited good to moderate activity.
- Murty, M. S. R.,Rao, B. Ramalingeswara,Ram, Kesur R.,Yadav, J. S.,Antony, Jayesh,Anto, Ruby John
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p. 3161 - 3169,9
(2020/08/20)
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- Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands
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A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D3 receptor, low or no affinity at the D1 and D2 receptors. Compounds 7f and 11c stood out as the most potent at the D3 receptor among our newly synthesized aporlogues with Ki values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT1A receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with Ki values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D3 over 5-HT1A receptors. Such D3/5-HT1A dual property of these compounds may be useful in the treatment of several brain disorders.
- Ye, Na,Wu, Qianqian,Zhu, Liyuan,Zheng, Longtai,Gao, Bo,Zhen, Xuechu,Zhang, Ao
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experimental part
p. 1999 - 2008
(2011/04/26)
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- Synthesis and in vitro evaluation of novel indole-based sigma receptors ligands
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To investigate the molecular features involved in sigma (σ) receptors binding, a series of compounds based on indole scaffolds were synthesized and their chemical structures were confirmed by 1H-NMR, IR, and elemental analysis. Their affinity t
- Yarim, Mine,Koksal, Meric,Schepmann, Dirk,Wuensch, Bernard
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experimental part
p. 869 - 875
(2012/07/03)
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- Preparation of piperazine derivatives as 5-HT7 receptor antagonists
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Twenty-four compounds of 4-methoxy-N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] benzene sulfonamides and N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] naphthyl sulfonamides were prepared and evaluated as 5-HT7 receptor antagonists. Most of the compounds showed the IC50 values of 12-580 nM. Four methyl branched analogues were also obtained, but the activity for methyl branched analogues was almost same as its straight chain congeners. Among the synthesized compounds, 3c showed a good activity on 5-HT7 receptors and a good selectivity on 5-HT1a, 5-HT2a, 5-HT2c, and 5-HT6 receptors.
- Yoon, Juhee,Yoo, Eun A,Kim, Ji-Yeon,Pae, Ae Nim,Rhim, Hyewhon,Park, Woo-Kyu,Kong, Jae Yang,Park Choo, Hea-Young
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p. 5405 - 5412
(2008/12/21)
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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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- New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors.
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A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.
- Gonzalez-Gomez,Santana,Uriarte,Brea,Villazon,Loza,De Luca,Rivas,Montenegro,Fontenla
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p. 175 - 178
(2007/10/03)
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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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- 2-{4-[3-(4-Aryl/heteroaryl-1-piperazinyl)propoxy]phenyl}-2H-benzotriaz-oles and their N-oxides as ligands for serotonin and dopamine receptors
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A small set of 2-{4-[3-(4-aryl/heteroaryl-piperazinyl)propoxy]phenyl}-2H-benzotriazoles and corresponding N-oxides were prepared. The synthesized compounds were able to bind on some serotonin (5-HT(1A), 5-HT(2A)) and dopamine (D2, D3
- Sparatore, Anna,Goegan, Mara,Cagnotto, Alfredo,Sparatore, Fabio
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p. 402 - 410
(2007/10/03)
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- Phenylpiperazine derivatives with strong affinity for 5HT(1A), D(2A) and D3 receptors
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Four 7-[3-(4-phenyl-1-piperazinyl)propoxy]coumarins were synthesized. The affinities of these compounds for DA (D(2A), D3) and 5HT(1A) receptors were evaluated for their ability to displace [3H]-raclopride and [3H]-8- OH-DPAT respectively from their specific binding sites. The affinities of the target compounds were all in the nanomolar range and followed the order 5- HT(1A) > D2 > D3.
- Teran, Carmen,Santana, Lourdes,Uriarte, Eugenio,Fall, Yagamare,Unelius, Lena,Tolf, Bo-Ragnar
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p. 3567 - 3570
(2007/10/03)
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- BENZIMIDAZOLES AND IMIDAZOPYRIDINES AS CENTRAL NERVOUS SYSTEM AGENTS
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Benzimidazoles and imidazopyridines are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful as central nervous system agents and are particularly useful as antipsychotic agents and for the treatment o
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- Synthesis and trazodone-like pharmacological profile of 1- and 2--propyl>benzotriazoles
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A series of 1- and 2--propyl>benzotriazoles were prepared and evaluated for their trazodone-like pharmacological profile; as preliminary pharmacological screening, the compounds were tested for their antiserotonergic, antiadrenergic and antihistaminic in vitro activity as well as for their analgesic in vivo action.Structure-activity relationships showed that among the synthesized compounds, the analogues bearing on the 4-piperazine nitrogen either an unsubstituted phenyl ring or a 2- or 3-chloro phenyl moiety show a pharmacological profilesimilar to that of the antidepressant trazodone. benzotriazoles / antiserotonergic / antiadrenergic / antihistaminic/ analgesic
- Caliendo, G.,Carlo, R. Di,Meli, R.,Perissutti, E.,Santagada, V.,et al.
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p. 969 - 974
(2007/10/02)
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- Dopamine Autoreceptor Agonists as Potential Antipsychotics. 1. (Aminoalkoxy)anilines
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The synthesis and pharmacological properties of a novel type of anilines with dopaminergic properties are described.One of these compounds, 3-benzeneamine (4c), has been identified as a selective
- Jaen, Juan C.,Wise, Lawrence D.,Heffener, Thomas G.,Pugsley, Thomas A.,Meltzer, Leonard T.
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p. 1621 - 1625
(2007/10/02)
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- N-Aryl-N-phenoxy-alkyl-piperazine compounds useful in decreasing intracranial pressure
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A piperazine derivative of the formula: STR1 wherein R1 is hydrogen, alkyl (C1-8), alkyl (C1-4)-sulfonyl or an acyl group of the formula: R3 CO--(wherein R3 is hydrogen, alkyl (C1-7), halogenoalkyl (C1-4), alkoxy (C1-4)-carbonyl-alkyl (C1-4), cycloalkyl (C3-6), alkenyl (C2-5), alkoxy (C1-4), amino, alkyl (C1-4)-amino or anilino), R2 is hydrogen, alkyl (C1-4), alkoxy (C1-4)-carbonyl-alkyl (C1-4), carboxy-alkyl (C1-4), alkenyl (C2-5) or alkyl (C1-4)-sulfonyl, or R1 and R2 are combined together to form succinyl group, Ring A is phenyl, alkyl (C1-4)-phenyl or halogenophenyl, and n is an integer of 2 to 6, or a pharmaceutically acceptable acid addition salt thereof. The piperazine derivative (I) has an intracranial pressure-lowering activity. Said derivative also has a depressing effect on central nervous system.
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- Synthesis and Biological Activities of 3-Substituted 1-Aryloxyaminopropanes
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A number of 3-substituted 1-aryloxyaminopropanes (9-43) have been prepared by the reaction of appropriate hydroxyaryl compound with 1-chloro-3-1-(N4-aryl-piperazinyl/piperidinyl)>propanes (1-8).The 1-(6/7-quinolyloxy)-3-substituted
- Agarwal, Shiv K.,Kumar, Yatendra,Saxena, Anil K.,Jain, Padam C.,Anand, Nitya
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p. 435 - 439
(2007/10/02)
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