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At least 235 records · Page 13Linked to original sources
PubMed2001

Mass spectrometric studies on small open-chain piperazine-containing ligands and their transition metal complexes.

Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry was used to characterize the complexes formed between open-chain piperazine-containing ligands and transition metal salts (Cobalt, Copper, Zinc, and Cadmium as chlorides, nitrates, and acetates). Only single-charged complexes were observed, formed of one ligand (L) and mainly one metal ion (M). Since the net charge of the complexes was one, a counterion (X) was attached to some of the complexes, with formation of [L + M + X]+ complexes, and a proton was lost from others, as in [L - H + M]+ complexes. In most cases the composition of the complexes was more dependent on the ligand than the metal salt. Collision-induced dissociation measurements showed that complexes with related composition often differed in structure, or that interactions between the ligand and the metal ion were not alike. The metal ion influenced considerably the fragmentation pathways of the ligands, so that the fragmentation products could be used to deduce the binding sites of the metal. The variations observed in fragmentation behavior of complexes possessing the same ligand but different metal ions can mostly be explained by the ionic radius and electronic configuration of the metal ion. The results indicated a preference of the piperazine ring of the coordinated ligand for the boat conformation.

Cobalt↗
PubMed1976

Photochromism of an anticonvulsant, 1-diphenylmethyl-4-(6-methyl-2-pyridylmethylene-amino) piperazine, in the solid state.

The light-induced color change of 1-diphenylmethyl-4-(6-methyl-2-pyridylmethyleneamino) piperazine in the solid state was investigated. Light in the 420-700-nm visible region had no effect. Elevated temperature, dissolution, or prolonged storage in the dark at room temperatures restored the intrinsic color of the compound. IR, UV (solution), NMR, differential scanning calorimetry, and GC methods showed no detectable difference between the long wave-length UV light-exposed (yellow) and unexposed (colorless) samples of the pure compound. Long wavelength UV light exposure studies with several substituted piperazine analogs revealed a structure-activity requirement for the color conversion process. The data indicated that the transformation process from colorless (or faint yellow) to bright yellow is photochromism (phototropy) and is dependent on the intensity of the "action spectrum" in the 300-400-nm region. Studies in the solid state showed that heat-induced fading of the color followed apparent zero-order kinetics. The energy of activation, Eb, for the photochromic conversion process from the metastable (yellow) to the stable (colorless) state was estimated to be about 19 kcal/mole.

Anticonvulsants↗
PubMed1978

Synthesis and quantitative structure-activity relationships of antibacterial 1-(substituted benzhydryl)-4-(5-nitro-2-furfurylideneamino) piperazines.

1-Benzhydryl -4- (5-nitro-2-furfurylideneamino) piperazine and 11 substituted analogs were prepared and examined for in vitro antimicrobial activity. The compounds were active against Bacillus cereus 7, Bacillus megaterium 122, Bacillus subtilis 104, Clostridium perfringens 13, and the tetracycline-resistant Clostridium perfringens 37. Regression analyses on the antibacterial activity data based on the Hansch approach, using pi, pi2, and sigma parameters, yielded several statistically significant correlation equations. 1-Benzhydryl-4-(5-nitro-2-furfurylideneamino) piperazine stopped the protein and DNA syntheses in C. perfringens 13, as indicated by precipitable radioactivity. The compound, however, showed no effect on the cell wall synthesis in the bacteria.

Anti-Bacterial Agents↗
PubMed2006

Novel water-soluble quaternary piperazine derivatives of chitosan: synthesis and characterization.

Novel synthesis methods for the preparation of quaternary piperazine derivatives of chitosan were developed. Quaternary ammonium moiety can be selectively inserted into either one or both of the piperazine nitrogens, yielding structurally uniform chitosan derivative structures. Water-soluble end products were thoroughly characterized with FT-IR, 1H NMR, 13C NMR and 2D 1H-13C HSQC NMR. The molecular weights of the end products were determined by GPC with triple detection.

Biocompatible Materials↗
PubMed1998

Copper(II) complexation properties and surfactant activity of 3-[N, N-bis(2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid and N-(2-Hydroxyethyl)piperazine-N'-2-hydroxypropanesulfonic acid pH buffers which may affect trace metal speciation in in vitro studies.

Disadvantages of the some zwitterionic pH buffers are (i) that they can interact with metal ions as well as protons, and (ii) that they may have a surfactant effect in chemical or in vitro biological or biochemical studies. This has to be taken into account when a buffer is selected. Here, the copper-complexing capacity and the surfactant activity of three compounds, 3-[N,N-bis (2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (DIPSO), N-(2-hydroxyethyl)piperazine-N'-(2-hydroxypropanesulfonic acid) (HEPPSO), and piperazine-N,N'-bis(2-ethanesulfonic acid) (Pipes), were investigated. Global stability constants (log betaabc) of copper(II)-buffer complexes were determined, at 25 degrees C, 0.5 M ionic strength, and at 0.8 mM buffer concentration, by pH and pCu ion-selective electrode measurements. Here, betaabc corresponds to the equilibrium: aCu2+ + bL- + cH+ left and right arrow (CuaLbHc)(2a-b+c); HL = DIPSO or HEPPSO; c: +1 = proton; -1 = hydroxide. Using SUPERQUAD constants were calculated, giving: DIPSO: log beta110 = 5.02, log beta120 = 8.99, log beta130 = 13.0, log beta140 = 16.3, log beta14-1 = 9.26, log beta14-2 = 0.645, log beta150 = 20.5, log beta160 = 24.3, log beta16-1 = 16.1, log beta16-2 = 8.98; HEPPSO: log beta110 = 4.29, log beta120 = 8.35, log beta130 = 12.1, log beta140 = 15.9, log beta150 = 19.6, log beta160 = 23.4, log beta16-1 = 14.9. The pKa values were determined at higher buffer concentrations, giving a value 7.33 for DIPSO and 7.84 for HEPPSO at 2.0 mM buffer concentration. Effects of buffer concentration on stability and acidity constants were investigated and compared with measurements using voltammetric and potentiometric stripping analysis, confirming no copper(II) complexation by Pipes. Surfactant activities were determined using alternating current polarography, confirming marked surface activity of 10 mM of DIPSO or HEPPSO.

Buffers↗
PubMed1984

Serotonin-releasing effects of substituted piperazines in vitro.

The effects of various piperazine-containing compounds on the release of endogenous serotonin (5-HT) from rat hypothalamic slices were evaluated. Incubation of hypothalamic slices with m-chlorophenylpiperazine ( mCPP ) or m- trifluoromethylphenylpiperazine ( mTFMPP ) evoked a potent, dose-dependent release of endogenous 5-HT that was similar in magnitude to that seen with tryptamine, p-chloroamphetamine, or fenfluramine. In the presence of the 5-HT uptake blockers fluoxetine or chlorimipramine, this release was reduced dramatically. Furthermore, removal of calcium from the incubation medium had little effect on the drug-induced release, suggesting that the release mechanism involved displacement of 5-HT stores and not depolarization-induced exocytosis. Trazodone, MK-212, and quipazine had only small effects on release. These studies show that several piperazine-containing compounds can evoke a potent release of endogenous stores of hypothalamic 5-HT in vitro, actions which should be considered together with their direct agonist activity when interpreting the CNS effects in vivo.

Animals↗
PubMed1995

[3H]GBR 12935 labels mainly the piperazine acceptor site in the rat prefrontal cortex.

The binding characteristics of [3H]GBR 12935, a ligand for the dopamine (DA) transporter, have been extensively investigated in the striatum. The present study was designed to characterize [3H]GBR 12935-binding to prefrontal cortex (PFC) in rats. This region receives a dense DA input from the ventral tegmental area and is suspected to play a major role in higher associative functions. We demonstrated high-affinity, saturable, mazindol-sensitive [3H]GBR 12935-binding in the rat PFC; however, in contrast to the striatum, such binding was inhibited by increasing concentrations of Na+. This fact, together with the irregular pattern of the association kinetics and the marked sensitivity of [3H]GBR 12935-binding to piperazine derivatives, indicates the possible presence of more than one [3H]GBR 12935-binding site in the PFC. Furthermore, it appears that [3H] 12935 in the rat PFC labels mainly 'the piperazine acceptor site' and not the DA transporter.

Animals↗
PubMed1992

The effects of intraventricular administration of eltoprazine, 1-(3-trifluoromethylphenyl)piperazine hydrochloride and 8-hydroxy-2-(di-n-propylamino)tetralin on resident intruder aggression in the rat.

Various serotonergic agents may reduce aggression in rats, but how they act in different parts of the brain is unknown. This study attempted to unravel part of this question by application of different serotonergic ligands into the lateral ventricle (i.c.v.) of male rats (resident-intruder aggression). 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin; 1 and 10 micrograms), a specific 5-HT1A agonist, affected neither aggression nor any other behaviour. The mixed 5-HT1A,B,C agonist, TFMPP (1-(3-trifluoromethylphenyl)piperazine hydrochloride), and the 5-HT1A/1B agonist, eltoprazine ((1-(2,3)-dihydro-1,4-benzodioxin-5-yl)piperazine hydrochloride), suppressed aggression at i.c.v. doses of 10 and 30 micrograms. This reduction was not caused by sedation. These data suggest a role of postsynaptic 5-HT1B receptors in mediating the anti-aggressive effects of mixed 5-HT1 agonists.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Interaction between substituted 1-[2-(diphenylmethoxy)ethyl] piperazines and dopamine receptors.

Substituted 1-[2-(diphenylmethoxy)ethyl]piperazines were tested for their affinity to specific [3H]dopamine binding sites in membrane preparations from the corpus striatum of the rat. In particular, 4-(3-phenyl-2-prop(en)yl)- and 4-(3-phenyl-2-butyl)-substitution yielded compounds potent in displacing [3H]dopamine from its binding sites, with IC50-values in the order of 10 nM. There was a significant correlation between the IC50-values determined in this binding assay and the IC50-values obtained for the same compounds in a previous study on their potency to inhibit the uptake of dopamine in synaptosomal preparations of the striatum of the rat. Current insight in structural requirements for binding to dopamine receptors, as obtained mainly with rigid analogues of dopamine, gives no satisfactory explanation for the dopaminergic activity of the piperazine derivatives tested.

Animals↗
PubMed1991

Substituted piperazine and indole compounds increase extracellular serotonin in rat diencephalon as determined by in vivo microdialysis.

In vivo microdialysis was used to examine the effects of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU24969) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) on extracellular 5-hydroxytryptamine (5-HT) in the diencephalon of unanesthetized rats. Both RU24969 and TFMPP are potent 5-HT autoreceptor agonists but both compounds caused a dose-dependent increase in extracellular 5-HT, when infused into the diencephalon at micromolar concentrations. The piperazine compound, TFMPP, also caused an increase in 5-HT when administered peripherally (2.5-10 mg/kg i.p.). In contrast, peripheral administration of RU24969 (2.5 mg/kg i.p.) caused a decrease in extracellular 5-HT. Since the effects of local infusion with RU24969 and TFMPP were not additive with the increase produced by the inhibitor of the uptake of 5-HT, fluoxetine, these compounds may be acting at the site of the membrane carrier. These results suggest that direct 5-HT1 agonist activity is not the only factor involved in the physiological and behavioral consequences of peripheral administration of TFMPP.

Animals↗
PubMed1993

Carcinogenic effects in rats of nitrosopiperazines administered intravesically: possible implications for the use of piperazine.

Two nitrosamines derived from nitrosation of piperazine, 1-nitrosopiperazine (NO-PIP) and 1,4-dinitrosopiperazine (DNP), were administered to groups of twelve female F344 rats intravesically. The doses were, respectively, 40 mg and 5.2 mg twice a week for 48 and 36 weeks in aqueous solution. Ten DNP-treated animals survived the treatment; six had tumors related to the treatment, nasal mucosa adenocarcinomas or neuroblastomas in five and a transitional cell carcinoma of the bladder in one. Rats treated with NO-PIP received a ten times greater dose, and all died by week 59, two with transitional cell neoplasms of the bladder and four with carcinomas of the nasal mucosa. NO-PIP was probably in part converted by transnitrosation to DNP. Piperazine, widely used as an oral anti-helminthic, could interact with nitrosating agents in vivo to form the two nitrosamines here shown to pose a possible carcinogenic risk if present in the bladder, by absorption through the bladder wall.

Adenocarcinoma↗
PubMed2005

1-Aryl-4-(4-succinimidobutyl)piperazines and their conformationally constrained analogues: synthesis, binding to serotonin (5-HT1A, 5-HT2A, 5-HT7), alpha1-adrenergic, and dopaminergic D2 receptors, and in vivo 5-HT1A functional characteristics.

Starting with the structure of potent 5-HT(1A) ligands, that is, MM77 [1-(2-methoxyphenyl)-4-(4-succinimidobutyl)piperazine, 4] and its constrained version 5 (MP349), previously obtained in our laboratory, a series of their direct analogues with differently substituted aromatic ring (R=H, m-Cl, m-CF(3), m-OCH(3), p-OCH(3)) were synthesized. The flexible and the corresponding 1e,4e-disubstituted cyclohexane derivatives were designed in order to investigate the influence of rigidification on 5-HT(1A) affinity, selectivity for 5-HT(2A), 5-HT(7), D(1), and D(2) binding sites and functional profile at pre- and postsynaptic 5-HT(1A) receptors. The new compounds 19-25 were found to be highly active 5-HT(1A) receptor ligands (K(i)=4-44 nM) whereas their affinity for other receptors was: either significantly decreased after rigidification (5-HT(7)), or controlled by substituents in the aromatic ring (alpha(1)), or influenced by both those structural modifications (5-HT(2A)), or very low (D(2), K(i)=5.3-31 microM). Since a distinct disfavor towards rigid compounds was observed for 5-HT(7) receptors only, it seems that the bioactive conformation of chain derivatives at those sites should differ from the extended one. Several in vivo models were used to asses functional activity of 19-25 at pre- (hypothermia in mice) and postsynaptic 5-HT(1A) receptors (lower lip retraction in rats and serotonin syndrome in reserpinized rats). Unlike the parent antagonists 4 and 5, all the new derivatives tested were classified as partial agonists with different potency, however, similar effects were observed within pairs (flexible and rigid) of the analogues. The obtained results indicated that substitution in the aromatic ring, but not spacer rigidification, controls the 5-HT(1A) functional activity of the investigated compounds. Moreover, an o-methoxy substituent in the structure of 5 seems to be necessary for its full antagonistic properties. Of all the new compounds studied, trans-4-(4-succinimidocyclohexyl)-1-(3-trifluoromethylphenyl)piperazine 24 was the most potent 5-HT(1A) receptor ligand in vitro (K(i)=4 nM) and in vivo, with at least 100-fold selectivity for the other receptors tested.

Animals↗
PubMed2006

Structure-activity relationships in platelet-activating factor. Part 13: synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity.

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure-activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Antioxidative activities of novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter.

A new series of diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter (DAT), which were modified at both the diphenylalkyl moiety and the phenyl ring in the phenylamino moiety of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1, was evaluated for their inhibitory activities against auto-oxidative lipid peroxidation in canine brain homogenates. Some of these were approximately equivalent in activity to alpha-tocopherol as a potent antioxidant with IC(50) values of low micromolar order, and the 4-hydroxyphenyl derivative 11 showed the most potent antioxidative activity with an IC(50) value of 0.32 microM, exhibiting approximately 5-fold more potent activity than alpha-tocopherol. The structure-activity relationship (SAR) studies of the antioxidative activity of these derivatives are presented.

Animals↗
PubMed2005

Pharmacophore-based design, synthesis, biological evaluation, and 3D-QSAR studies of aryl-piperazines as alpha(1)-adrenoceptor antagonists.

Phenyl-piperazines were designed and synthesized based on pharmacophore for uro-selective alpha(1)-adrenoceptor antagonists and 3D chemical database searching. Within this series, three compounds, 2, 3, and 13, showed similar or better alpha(1)-AR antagonistic activity compared with prazosin. The 3D-QSAR study of these compounds may provide useful information for the development of novel aryl-piperazines as uro-selective alpha(1)-adrenoceptor antagonists, which can be used for the treatment of BPH with fewer side effects.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2006

Synthesis of new and potent analogues of anti-tuberculosis agent 5-nitro-furan-2-carboxylic acid 4-(4-benzyl-piperazin-1-yl)-benzylamide with improved bioavailability.

Previously, the lead compound 5-nitro-furan-2-carboxylic acid 4-(4-benzyl-piperazin-1-yl)-benzylamide was identified in our anti-tuberculosis drug discovery program. Although this compound demonstrated excellent in vitro activity, it did not meet the expected in vivo profiles due to structural features that resulted in rapid metabolic cleavage and poor absorption, which therefore limited its bioavailability. In efforts to increase the bioavailability, a new series of analogues was successfully synthesized using three modification schemes: replacement of the benzyl group on the piperazine C-ring with carbamate and urea functional groups; introduction of a nitrogen atom into the aromatic ring-B; and expansion of the ring-B to a bicyclic tetrahydroisoquinoline moiety. These modifications retained strong activity and in some case gained superior anti-tuberculosis activity, increased absorption, and serum half life.

Animals↗