- 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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- 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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- 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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- Antidiabetic piperazine derivatives, processes for their preparation and compositions containing them
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Piperazine derivatives of formula (I) wherein Z, X, n, Ar and i have the meanings defined herein are usefull in the treatment of pathologies associated with insulin-resistance syndrome.
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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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- Synthesis and biological activity of benzotriazole derivatives structurally related to trazodone
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This paper outlines the synthesis and the pharmacological screening of a series of novel 1- and 2-ethyl>benzotriazoles and 1-propoxy>benzotriazoles, which are structurally related to trazodone.Antiserotonergic, antiadrenergic and antihistaminic in vitro activity and in vivo analgesic action are described.Some of the investigated compounds show overall pharmacological profiles similar to that of the antidepressant trazodone. benzotriazole / antiserotonergic activity / antiadrenergic activity / antihistaminic activity / analgesic activity
- Caliendo, G.,Carlo, R. Di,Greco, G.,Meli, R.,Novellino, E.,et al.
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- Oxazolopyridine compounds, compositions and use
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The invention relates to the analgesic compounds of general formula (I): STR1 in which: R1, R2, R3, R4, A, Z and m are as defined in the description, their isomers, epimers and diastereoisomers, their addition s
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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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- (S)-1-[2-(4-HYDROXY-S-(1-ALKYLAMINO-PROPOXY)PHENYLALKYL]-4-PHENYLPIPERAZINES
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There are disclosed compounds of the formula STR1 wherein R 1 is selected from the group consisting of lower alkyl; R 8 is selected from the group consisting of--O--(CH 2) n--wherein n is 2 to 20, STR2 and R 6 is selected from the group consisting of hydrogen or lower alkoxy, and STR3 wherein R 1 is selected from the group consisting of lower alkyl; R 8 is selected from the group consisting of--O--(CH 2) n--wherein n is 2 to 20, STR4 and R 6 is selected from the group consisting of hydrogen or lower alkoxy and racemates thereof.There are also disclosed processes and intermediates utilized to produce the end products. The end products have utility as agents exhibiting both α and selective β adrenergic blocking action.
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- 1-Heterocyclic alkyl-1,2,3,4-tetrahydroquinazolinones
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1-Heterocyclic alkyl-1,2,3,4-tetrahydroquinazolinones, acid addition salts thereof, and intermediate compounds having analgesic properties. A representative quinazolinone compound is 1-[2-(1-phenyl-4-piperazinyl)-ethyl]-2-phenyl-1,2,3,4-tetrahydro-4-quina
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- 1-Heterocyclic alkyl-1,2,3,4-tetrahydroquinazolinones and analgesic intermediates thereof
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1-heterocyclic alkyl-1,2,3,4-tetrahydroquinazolinones, acid addition salts thereof, and intermediate compounds having analgesic properties. A representative quinazolinone compound is 1-[2-(1-phenyl-4-piperazinyl)-ethyl]-2-phenyl-1,2,3,4-tetrahydro-4-quinazolinone. A representative analgesic intermediate is 2-[2-(4-[1-phenyl]piperazinyl)ethylamino]benzamide.
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