- Synthesis and pharmacological screening of some N-(4-substituted-piperazin-1-ylalkyl)-3,4-pyrroledicarboximides
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As an extension of our previous work we describe the synthesis and pharmacological investigation of a new series of derivatives of pyrrole-3,4-dicarboximide possessing the 4-substituted-piperazin-1-ylalkyl group linked to the imide nitrogen. The products were evaluated for acute toxicity, and effectiveness in a series of CNS and arterial blood pressure tests. The preliminary pharmacological screening was determined in animal models. Several compounds demonstrated moderate to high analgesic activity in the 'writhing syndrome' test (5f-1/640 LD50). Some of the structure-activity relationships are also discussed.
- Malinka, Wieslaw,Sieklucka-Dziuba, Maria,Rajtar, Grazyna,Rubaj, Andrzej,Kleinrok, Zdzislaw
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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 0172-0175
(2019/02/10)
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- CONTINUOUS PROCESS FOR THE PREPARATION OF TRAZODONE
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The present invention relates to an improved process for the preparation of trazodone. In particular, the present invention relates to a continuous process for the preparation of trazodone. More in particular, the present invention relates to a new method for the preparation of trazodone, said method comprising at least one step consisting of a continuous process performed in a flow reactor.
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Page/Page column 23-25
(2019/08/29)
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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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- 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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- 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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- A search for new 5-HT(1A)/5-HT(2A) receptor ligands. In vitro and in vivo studies of 1-[ω-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones
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A series of 1-[ω-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5- HT(1A)/5-HT(2A) activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT(1A) (K(i) = 2 - 44 nM) and/or 5-HT(2A) affinity (K(i) = 51 and 39 for 5 and 7, respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these elects evoked by 8-hydroxy- 2-(di-n-propyl-amino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT(1A) receptors. The 5-HT(2A) antagonistic activity was assessed by the blocking effect on the head twitches induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-{3-[4-(3-chlorophenyl)-1- piperazinyl]propyl}-6-fluoroindolin-2(1H)-one (5) and 1-{3-[4-(2- methoxyphenyl)-1-piperazinyl]propyl}indolin-2(1H)-one (7), demonstrated a high 5-HT(1A)/5-HT(2A) affinity and an in vivo antagonistic activity towards both receptor subtypes.
- Mokrosz, Maria J.,Duszynska, Beata,Misztal, Stanislaw,Klodzinska, Aleksandra,Tatarczynska, Ewa,Chojnacka-Wojcik, Ewa,Dziedzicka-Wasylewska, Marta
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p. 325 - 330
(2007/10/03)
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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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- 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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- Triazoloquinolones
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2-[3-[4-Arylpiperazin-1-yl]propyl]-1,2,4-triazolo[4,3-a]-quinolin-3(2H)-ones are antidepressant agents.
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