Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Piperazines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources
PubMed1982

[The whole body autoradiographic studies on the distribution of 14C-labelled sodium 7 beta-[(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazine-carboxamido)-3-hydroxybutanamido]-7 alpha-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate (14C-T-1982) in mice].

The distribution of T-1982, a new semisynthetic cephamycin antibiotic, was studied with whole body autoradiography in normal male mice, pregnant mice and experimental pyelonephritic mice following a single intravenous administration of 80 mg/kg of 14C-T-1982. 1. In normal male mice, the radioactivity was distributed at high concentration in the liver, kidney, lung, gastrointestinal tracts, skin, salivary gland, tongue and muscle, but was hardly observed in the central nervous system that composed of the brain and spinal cord. 2. In pregnant mice, the radioactivity was hardly observed in the fetuses. 3. In experimental pyelonephritic mice, considerable radioactivity was concentrated on the acute inflammatory area.

Animals↗
PubMed2006

Axial coordination changes the morphology of porphyrin assemblies in an organogel system.

The gelation properties of a zinc porphyrin bearing peripheral urea groups (1 x Zn) were evaluated in the absence and the presence of several diamines. In aromatic solvents such as benzene, toluene and p-xylene, 1 x Zn only provided the precipitate. In contrast, 1 x Zn with 0.5 and 1.0 equiv. of piperazine formed gels, and the gel with 0.5 equiv. of piperazine showed a unique physical property called 'thixotropy'. On the other hand, upon addition of similar diamines such as DABCO, ethylenediamine and N,N'-dimethylethylenediamine, 1 x Zn did not gelate these solvents. When the critical gelation concentration was plotted against the ratio of piperazine versus 1 x Zn, it afforded a minimum breakpoint at 0.5 equiv. and the critical concentration increased with further increase in the fraction of piperazine, indicating that the stable gel is formed from the 1 x Zn + piperazine 2:1 complex and the subsequent transformation to the 1:1 complex rather destabilizes the gel. Very interestingly, it was clearly shown by SEM and TEM observations that such structural changes of the unit complex induced by the ratio of piperazine versus 1 x Zn can lead to gradual morphological transitions: that is, spherical structure at 0 equiv., 1-D fibrous structure at 0.5 equiv. and 2-D sheet-like structure at 1.0 equiv. In addition, UV-VIS spectra revealed that 1 x Zn itself adopts a J-aggregation mode, whereas 1 x Zn + piperazine 2:1 and 1:1 complexes adopt an H-like aggregation mode. On the other hand, upon addition of 0.5 equiv. of other diamines, 1 x Zn + diamine complexes result in different morphologies other than the 1-D fibrous structure. To explore a reasonable rationale for these results, we conducted computational studies. As a result, we found that the complex symmetry of the unit complex plays an important role in determining the final ordered structure.

Diamines↗
PubMed2002

Synthesis, structural evaluation, and estrogen receptor interaction of 2,3-diarylpiperazines.

To develop novel estrogen receptor (ER) ligands, ring-fused derivatives of the hormonally active (1R,2S)/(1S,2R)-1-(2-chloro-4-hydroxyphenyl)-2-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine 4b were synthesized. (2R,3S)/(2S,3R)-2-(2-Chloro-4-hydroxyphenyl)-3-(2,6-dichloro-4-hydroxyphenyl)piperazine 4 induced ligand-dependent gene expression in MCF-7-2a cells, stably transfected with the plasmid ERE(wtc)luc and was therefore used as a lead structure. The influence of the substitution pattern in the aromatic rings (4-OH (1), 2-F,4-OH (2), 2-Cl,4-OH (3), 2,6-Cl2,3-OH (5), and 2,6-Cl2,4-OH (6)) and the effect of N-ethyl chains on the ER binding and activation of gene expression were studied. The synthesis started from the respective methoxy-substituted (1R,2S)/(1S,2R)-configurated 1,2-diarylethylenediamines 6b to 4b, which were reacted with dimethyl oxalate in order to get 5,6-diarylpiperazine-2,3-diones. Reduction with BH3*tetrahydrofuran and ether cleavage with BBr3 yielded the piperazines 1-6. The N-alkylation of the piperazines 1a-3a, which was employed for obtaining compounds 7-11, was succeeded by acetic anhydride followed by reduction and ether cleavage. Nuclear magnetic resonance (NMR) spectroscopical studies revealed a synclinal conformation of the 1,2-diarylethane pharmacophore and a preference of the substituents at the heterocyclic ring for an equatorial position. This spatial structure prevents an interaction with the ER analogously to that of estradiol (E2). Therefore, the piperazines can displace E2 from its binding site only to a very small extent. Only the N-ethyl (8) and N,N'-diethyl (11) derivatives of piperazine 3 showed relative binding affinity values > 0.1% (8, 0.42%, and 11, 0.17%). Nevertheless, ER-mediated gene activation was verified for the piperazines 4 (20%), 6 (73%), 7 (34%), 8 (74%), and 11 (37%) (concentration, 1 microM; E2, 100% activation) on the MCF-7-2a cell line. O-methylation led to completely inactive compounds and showed the necessity of H bridges from the piperazines to the ER for activating gene expression.

Animals↗
PubMed2006

Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives.

Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity. The antiparasitic screening showed that compounds 18-24 exhibited higher activity against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H-benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2-(4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo than albendazole and exhibited the same efficacy as piperazine, but in twice lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2-ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%, 76%, and 77%, respectively.

Animals↗
PubMed1998

Isoindol-1-one analogues of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridyl)-p-iodobenzamido]ethyl]pipera zine (p-MPPI) as 5-HT1A receptor ligands.

In developing radioiodinated antagonists for in vivo imaging of 5-HT1A receptors with SPECT, a series of new arylpiperazine benzamido derivatives, including 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridyl)-p-iodobenzamido]ethyl]p iperazine (p-MPPI, 31) (Kd = 0.36 nM), as potential ligands for 5-HT1A receptors were reported previously. However, rapid in vivo metabolism may have caused the breakdown of the amide bond of [123I]-31 and rendered this agent obsolete as an in vivo imaging agent in humans. To improve the in vivo stability of 31, a series of cyclized amide analogues were designed and synthesized. In vitro binding, metabolic stability, and in vivo biodistribution of these new derivatives were investigated. Several five-membered-ring isoindol-1-ones displayed very high in vitro binding affinity, especially 2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-6-nitro-3-phenyl-2, 3-dihydroisoindol-1-one, 15, 3-hydroxy-6-iodo-2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}- 3- phenyl-2,3-dihydroisoindol-1-one, 18, and 6-iodo-2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-3-phenyl-2, 3-dihydroisoindol-1-one, 21, which showed Ki values of 0.05, 0.65, and 0.07 nM, respectively. The affinities for 5-HT1A receptors of other cyclized amide derivatives, 5-(4-bromophenyl)-1-{2-[4-(2-methoxyphenyl)- piperazin-1-yl]ethyl}pyrrolidin-2-one, 25, 5-(4-iodophenyl)-1-{2-[4-(2-methoxyphenyl)piperazin- 1-yl]ethyl}pyrrolidin-2-one, 27, and 2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-2,3-dihydro- isoindol-1-one, 29, were 1.09, 2.54, and 14.9 nM, respectively. Compared to [125I]-31, iodinated cyclized amide derivatives [125I]-21 and [125I]-27 displayed a slower metabolism in human liver microsomal and cytosolic preparations. Biodistribution of [125I]-21 and [125I]-27 in rats (after an i.v. injection) displayed moderate to low brain uptakes with little or no specific localization in hippocampal region, where 5-HT1A receptors are concentrated. These data indicate that the new iodinated ligands showed high binding affinities and better metabolic stability but displayed unexpectedly low selective binding to 5-HT1A receptors in vivo. Additional structural modifications may be needed to correct the unfavorable properties displayed for these iodinated cyclized amide derivatives for in vivo biodistribution in rats.

Aminopyridines↗
PubMed1986

[Biotransformation of selected gyrase inhibitors].

The common structure of the gyrase inhibitors norfloxacin, ciprofloxacin, pefloxacin, and ofloxacin is 3-carboxy-4-oxo-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-quinolone. Several biotransformations of these substances are reported in the literature, mostly in animals and partly in humans: 1. Conjugation of the carboxylic acid to glucuronic acid (formation of an O-methyl ester of norfloxacin was found only in the rat); 2. Oxidation of the piperazine ring to the oxo derivative and subsequent metabolisation (or degradation) of the piperazine ring to several intermediates and finally to elimination of the side chain; 3. Substitution of the piperazine side chain to the 4-N-acetyl or 4-N-formyl-derivative (norfloxacin, ciprofloxacin); 4. Methylation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). 5. N-oxidation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). The glucuronides are microbiologically inactive. The activity of metabolites with a modified piperazine side chain varies from high (oxo derivatives) to low (after splitting of the ring). Quantitative data on the formation of the described transformation products in humans are presently still incomplete. The oxo derivative appears to be the main metabolite of norfloxacin and ciprofloxacin. Additional metabolites to the described ones are likely to be detected in the near future.

Anti-Infective Agents↗
PubMedDate not supplied

Evidence that blood pressure reduction by serotonin antagonists is related to alpha receptor blockade in spontaneously hypertensive rats.

In vitro affinity for vascular 5HT2 and alpha receptors was determined for several compounds (spiperone, ketanserin, mianserin, trazodone, mepiprazole, benzoctamine, m-trifluoro-methylphenylpiperazine, m-chlorophenylpiperazine, and 1-(1-naphthyl)piperazine) known to interact with serotonin receptors. All compounds competitively inhibited 5HT2 and alpha receptors with differing degrees of selectively. Based on these observations, ketanserin, benzoctamine, and 1(1-naphthyl)piperazine were evaluated as antihypertensive agents in spontaneously hypertensive rats (SHR). Of these compounds, 1-(1-naphthyl)piperazine was a highly selective 5HT2 receptor antagonist with a ratio of 5HT2 to alpha receptor affinity of greater than 2000. The ratio of 5HT2 to alpha receptor affinity for ketanserin and benzoctamine was 63 and 16, respectively. However, the order of affinity toward 5HT2 receptors was ketanserin greater than 1-(1-naphthyl)piperazine greater than benzoctamine whereas the order of affinity toward alpha receptors was ketanserin greater than benzoctamine greater than 1-(1-naphthyl)piperazine. A similar order of potency toward both 5HT2 and alpha receptors was found in pithed SHR based on antagonism of the pressor response to serotonin and methoxamine, respectively. In the SHR, maximum blood pressure reduction at a dose of 10 mg/kg i.p. was approximately 65 and 30 mm Hg for ketanserin and benzoctamine, respectively; 1-(1-naphthyl)piperazine did not affect blood pressure. Thus, blood pressure reduction more closely paralleled the in vitro and in vivo potency of these agents toward vascular alpha rather than 5HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The influence of bicarbonate ions on the GABA-mimetic activity of ethylenediamine.

A study was performed to investigate the GABA-mimetic activity of ethylenediamine (EDA) and piperazine at mammalian gamma-aminobutyric acid (GABA) receptors using radioligand binding assays and in vitro isolated tissues. The potency of ethylenediamine and piperazine as inhibitors of the binding of GABA receptors to synaptic membranes from rat brain was measured in Tris-buffers and Krebs-Henseleit solution (KHS). The potency of ethylenediamine and piperazine at GABAA and ethylenediamine at GABAB receptors was raised if Krebs-Henseleit solution was used for the assay. Piperazine was inactive at GABAB receptors. The potency of the antagonist of GABAA receptors bicuculline methobromide, was also increased in Krebs-Henseleit when compared with Tris-citrate buffer. Of the ions present in Krebs-Henseleit, bicarbonate ions were responsible for the increase in the GABA-mimetic potency of ethylenediamine and piperazine. Addition of either NaHCO3 or KHCO3 (25 mM) to Tris-HCl buffer (for GABAA binding) or Tris-HCl plus 2.5 mM CaCl2 (for GABAB binding) yielded IC50 values similar to those measured in Krebs-Henseleit solution. Bicarbonate ions also enhanced the ability of ethylenediamine to potentiate the binding of [3H]diazepam to membranes from rat brain (raising both the potency of ethylenediamine and its maximum effect) in this system. In the absence of HCO-3 ions, ethylenediamine potentiated the binding of [3H]diazepam by raising the maximum binding capacity (Bmax) without changing the affinity (Kd) of the receptors. Potassium bicarbonate (25 mM) caused ethylenediamine to further potentiate the binding of [3H]diazepam by changing both Bmax and Kd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification of a GBR12935 homolog, LR1111, which is over 4,000-fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters.

The di-substituted piperazines, GBR12909 (1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-[3- phenylpropyl]piperazine) and GBR12935 (1-[2-(diphenyl-methoxy)-ethyl]-4-(3-phenylpropyl)piperazine), are potent and selective (20-to 100-fold) inhibitors of [3H]dopamine reuptake, relative to [3H]5-HT and [3H]norepinephrine uptake. The GBR12935 analog, 1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)homopiperazine (LR1111), was synthesized as part of a systematic structure-activity study of analogs of GBR12935 and GBR12909. LR1111 differs from GBR12935 by the addition of a methylene group into the piperazine ring to yield a compound with a seven-member homopiperazine ring. The IC50 values for LR1111 at the dopamine, norepinephrine, and serotonin transporters were 7.2 nM, 34,072 nM, and greater than 20,000 nM, respectively, whereas the IC50 values of GBR12935 were 3.7 nM, 289 nM, and 1261 nM for these same transporters. This demonstrates that the addition of a single methylene group in the piperazine ring results in a compound with similar affinity but significantly higher selectivity for the dopamine transporter. LR1111 increased motoric activity in rats after intravenous administration. These indicate that LR1111 is a potent and highly selective inhibitor of the dopamine transporter.

Animals↗
PubMed1993

d-Fenfluramine- and d-norfenfluramine-induced hypophagia: differential mechanisms and involvement of postsynaptic 5-HT receptors.

Severe depletion of 5-hydroxytryptamine (5-HT) by para-chlorophenylalanine (pCPA, 150 mg/kg per day x3) did not alter the hypophagic effect of d-fenfluramine (1-3 mg/kg i.p.) 1 h after food presentation in 24-h food-deprived rats, and moderately and comparably increased the hypophagic effects of its metabolite, d-norfenfluramine (0.35-1.0 mg/kg i.p.), and of the 5-HT1C receptor agonist, 1-(3-chlorophenyl)piperazine (mCPP; 1.5, 2.0 mg/kg i.p.). Chronic treatment with mCPP (2.5 mg/kg i.p. x 14) attenuated the hypophagia induced by d-norfenfluramine (1, 1.5 mg/kg) but not d-fenfluramine (1, 3 mg/kg). 1-(1-Naphthyl)piperazine (3, 8 mumol/kg s.c.), which has greater affinity for 5-HT1C than for 5-HT2 receptors, had no effect on the hypophagia induced by d-fenfluramine (1.25, 2.0 mg/kg), but 1.3 and 3 mumol/kg 1-(1-naphthyl)piperazine largely and comparably attenuated the substantial hypophagic effect of d-norfenfluramine (0.75 mg/kg). The essentially complete hypophagic action of d-norfenfluramine (1.25 mg/kg) was inhibited by 1-(1-naphthyl)piperazine with ID50 = 2.13 mumol/kg. Ketanserin, which binds more weakly than 1-(1-naphthyl)piperazine to 5-HT1C receptors and more strongly to 5-HT2 receptors, attenuated weaker but not stronger hypophagic effects of d-fenfluramine (1.25, 2.0 mg/kg) when given at high dosage (8, 16 mumol/kg s.c.). Ketanserin (16 mumol/kg) also weakly attenuated the hypophagia due to d-norfenfluramine (0.75 mg/kg), but not the essentially complete hypophagia due to d-norfenfluramine (1.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

O-526, a piperidine analog of GBR 12909, retains high affinity for the dopamine transporter in monkey caudate-putamen.

1,4-Disubstituted piperazines such as GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) and GBR 12935 (1-[2-(bis(phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) are among the most potent and selective ligands for the dopamine transporter in brain. However, they also bind to a widely distributed "piperazine acceptor site". In order to assess whether the piperazine moiety of GBR 12909 is critical for binding to the dopamine transporter, two piperidine analogs of GBR 12909, one with the nitrogen proximal to the diphenylmethyloxy moiety (O-549, (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperidine), the other distal to this moiety (O-526, 4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1- (3-phenylpropyl)piperidine) were synthesized. The affinities of O-526, O-549 and GBR 12909 for the dopamine and serotonin transporters in monkey caudate-putamen (Macaca fascicularis) were evaluated using [3H]WIN 35,428 ([3H]CFT, 2 beta-carbomethoxy-3 beta-4-(fluorophenyl)tropane) or [3H]GBR 12935 and [3H]citalopram to label the dopamine and serotonin transporters, respectively. O-526 inhibited [3H]WIN 35,428 binding with potencies that were similar to GBR 12909 (IC50: 24.9 +/- 3.23 vs. 22.0 +/- 2.2 nM, respectively) whereas O-549 was 24 times less potent than O-526 (IC50: 595 +/- 148 nM). The selectivity of GBR 12909 for the dopamine over the serotonin transporter was retained by O-526 but not by O-549 which was relatively non-selective. These results indicate that only one of the two nitrogens on the basic GBR structure is needed for high affinity binding to the dopamine transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

The putative 5-HT1A receptor antagonist DU125530 blocks the discriminative stimulus of the 5-HT1A receptor agonist flesinoxan in pigeons.

Twelve homing pigeons were trained to discriminate the 5-HT1A receptor agonist flesinoxan (0.25 mg/kg p.o.) from its vehicle in a fixed ratio (FR) 30 two-key operant drug discrimination procedure. Tests for generalization and antagonism showed that compounds with agonistic action at the 5-HT1A receptor, such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), buspirone and ipsapirone all substituted for the flesinoxan cue. Compounds with mixed agonistic action at the 5-HT(1A/1B) receptor fully (eltoprazine) or partially (RU24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl-1H-indole)) substituted for flesinoxan. TFMPP (1-(3-trifluoromethylphenyl)piperazine) and mCPP (1-(3-chlorophenyl)piperazine), both acting at the 5-HT(1B/2C) receptor, did not substitute for flesinoxan, neither did the selective 5-HT re-uptake inhibitor fluvoxamine. The results of the antagonism tests showed that the 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine), WAY 100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-he xane-carboxamide) and the newly developed DU125530 (2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl ]butyl]-1,2-benzisothiazol-3(2H)-one-1,1-dioxide) fully (more than 80%) blocked the flesinoxan cue without having substantial effects when given alone. WAY100135 (N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide ), (+/-)-pindolol and (S)-UH-301 ((S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin) all partially antagonized the flesinoxan cue. However, both WAY100135 as well as (+/-)-pindolol also partially substituted for flesinoxan in generalization tests. NAN190, (S)-UH-301, WAY100635 and DU125530 were without any activity in the generalization test at the doses tested. The putative 5-HT1A receptor antagonist S15535 (4-benzodioxan-5-yl) 1-(indan-2-yl)piperazine) was identified as a full agonist in the present procedure. Taken together these results suggest that the flesinoxan cue in pigeons is mediated by the 5-HT1A receptor and that DU125530 acts as a full antagonist on the 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Structure-affinity relationship study on N-[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamides as potent and selective dopamine D(3) receptor ligands.

The benzamide PB12 (N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide) (1), already reported as potent and selective dopamine D(4) receptor ligand, has been modified searching for structural features that could lead to D(3) receptor affinity. Changes in the aromatic ring linked to N-1 piperazine ring led to the identification of 2-methoxyphenyl and 2,3-dichlorophenyl derivatives (compounds 6 and 13) displaying moderate D(3) affinity (K(i) = 145 and 31 nM, respectively). Intermediate alkyl chain elongation in compounds 1, 6, and 13 improved binding affinity for the D(3) receptor and decreased the D(4) affinity (compounds 18-26). Among these latter compounds, the N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (19) was further modified with the replacement or of the 2,3-dichlorophenyl moiety (compounds 27-30) or of the 3-methoxyphenyl ring (compounds 31-41). In this way, we identified several high-affinity D(3) ligands (0.13 nM < K(i)'s < 4.97 nM) endowed with high selectivity over D(2), D(4), 5-HT(1A), and alpha(1) receptors. In addition, N-[4-[4-(2,3-dimethylphenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (27) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (41) appear to be valuable candidates for positron emission tomography (PET) because of their affinity values, lipophilicity properties, and liability of (11)C labeling in the O-methyl position.

Animals↗