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 1,459 records · Page 81Linked to original sources
PubMed2003

Piperazine quaternary diammonium salts as additives to background electrolytes in capillary zone electrophoresis.

The differential behavior of five different quaternary mono- and diammonium salts, among the 18 investigated, in modulating the electroendoosmotic flow (EOF) and analyte separations in capillary zone electrophoresis is evaluated. It is found that quaternary diammonium salts with positive charges separated by more than four carbon atoms, while exhibiting a very strong affinity for chromatographic silica beads, to the point of exhibiting Rf values close to zero, display, on the contrary, a very poor affinity for the silica wall of capillaries. Compounds separated only by a C2 unit (i.e., 1,4-dialkyl-1,4-diazoniabicyclo[2,2,2,]octane, salts 17 and 18) show high Rf values due to strong ion pair association. The unique behavior of quaternary monoammonium salts possessing an iodinated alkyl (butyl or octyl) tail (i.e., 1, 6, and 7) is attributed to their ability to be covalently affixed to the silica wall via alkylation of ionized silanols at alkaline pH values. They thus strongly modulate and typically invert the EOF, even when not present in the background electrolyte. On the contrary, all diammonium salts, devoid of such alkyl tails, are unable to modulate the EOF and to prevent analyte binding to the silica wall, since they are rapidly removed from the wall by the voltage gradient. However, if added in small amount to the background electrolyte, they offer excellent separations of mixtures of very similar organic acids and prevent any interaction with the capillary wall.

Chromatography, Thin Layer↗
PubMed1979

Studies on the absorption, distribution and elimination of 6-o-chlorophenyl-2,4-dihydro-2(N-methyl-piperazin-1-yl)-methylene-8-nitro-1H-imidazo[1,2-a] [1,4]benzodiazepin-1-one methanesulphonate in the male rat and rabbit.

The fate of a novel imidazo-benzodiazepine (I) was studied in male rats and rabbits using 14C and 3H-labelled I. In both species the compound was rapidly and widely absorbed after an oral dose of 5 mg/kg to give peak tissue and plasma levels after 1 hour in the rat and 4 hours in the rabbit. The highest concentrations of radioactivity were present in the liver (rat) and liver, kidney and subcutaneous fat (rabbit). Plasma levels of radioactivity fell to 3% of the maximum value in 24 hours in the rat but 48 hours were required for a similar fall in the rabbit. The main route of elimination of radioactivity was via the bile followed by excretion in the faeces. For the rat the rate of biliary elimination was 16.6% of the administered dose/hour; for the rabbit this rate was 5.6%/hour. Recovery of administered radioactivity during 0-24 hours for urine and faeces respectively was 4.8% and 69% for the rat and 23.2% and 10.9% for the rabbit. Up to 97% of the radioactivity administered to rats could be recovered in the excreta in the 7 days following dosing. Up to 90% of the dose administered to rabbits appeared in the excreta during 10 days. No unchanged (I) could be detected in the urine or bile. The radioactive metabolites were polar products, some of which were in the form of glucuronide conjugates.

Animals↗
PubMed1987

A water-soluble derivative of prazosin prazosinamine hydrochloride [1-(4'-amino-6',7'-dimethoxyquinazolin-2'-yl)-4-(6''-aminohexanoyl) piperazine hydrochloride], reversibly inhibits the calcium-mobilizing action of alpha 1-adrenergic agonists in the perfused rat liver.

A newly-synthesized derivative of prazosin, prazosinamine hydrochloride, was examined for its ability to antagonize the interaction of the alpha 1-adrenergic agonist phenylephrine with liver cells. Using a Ca2--selective electrode to measure changes in perfusate Ca2+ concentration, prazosinamine was found to be as effective as prazosin in inhibiting the phenylephrine-induced efflux of Ca2+ from the perfused liver. Maximal and half-maximal inhibition occurred at 150 nM and 25 nM prazosinamine, respectively. Prazosinamine appears to share the alpha 1-specificity of prazosin, but has other unique and desirable properties. Its solubility in aqueous media is about three orders of magnitude higher than that of prazosin. Also, its antagonistic effects are rapid in onset, and are reversed within seconds of terminating its infusion into the liver. These attributes seem to make this agent more useful than prazosin for adrenergic receptor studies in perfused tissues. The molecule can also be readily coupled to other ligands.

Animals↗
PubMed1984

Discriminative stimulus properties of the serotonin agonist 1-(3-trifluoromethylphenyl)piperazine (TFMPP).

Using a standard two-lever drug discrimination procedure, twelve rats were trained to discriminate 1.0 mg/kg of the serotonin (5-HT) agonist TFMPP from saline. Once trained, the animals displayed a dose-related decrease in discriminative performance upon administration of lower doses of TFMPP. Tests of stimulus generalization were performed using the purported 5-HT agonist RU-24, 969 and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). While TFMPP produced stimulus effects similar to those of RU-24,969, these effects seem to be dissimilar to those of DOM. The results of the present study suggest that the discriminative stimulus effects of TFMPP may involve a 5-HT1-related mechanism.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1991

High-performance liquid chromatographic assay of alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a potential antipsychotic drug, in monkey and rat plasma.

A high-performance liquid chromatographic-fluorescence method was developed for the quantitative analysis of BMY-14802 (I) in monkey and rat plasma. After the addition of the internal standard (BMY-14853 I.S.), 250 microliters of plasma were made basic by the addition of 2 ml of saturated sodium carbonate buffer. Compound I and the I.S. were then extracted into 5 ml of methyl tert.-butyl ether. The organic phase was evaporated and the resulting residue was reconstituted in mobile phase. Final separation and quantitation of I was achieved on an octadecyl column with a 0.05 M potassium phosphate-acetonitrile-triethylamine-85% phosphoric acid (650:350:0.1:0.05, v/v) mobile phase. Fluorescence detection was used to monitor the eluent at an excitation wavelength of 240 nm and an emission wavelength of 400 nm. The limit of detection was 0.5 ng/ml. The standard curve was linear over the range 5.0-1000 ng/ml. Intra-assay and inter-assay precision values were less than 4.0% relative standard deviation and accuracy was within 12% of nominal values. Compound I was shown to be stable in monkey and rat plasma for at least six months when stored at -20 degrees C.

Animals↗
PubMed1985

The effect of low-dose piperazine oestrone sulphate and low-dose levonorgestrel on blood lipid levels in post-menopausal women.

Prolonged used of oestrogens has been shown to reduce the risk of arteriosclerotic heart disease by increasing the levels of circulating high density lipoprotein cholesterol. It has also been shown that progestogens derived from the 19-nortestosterone molecule will reverse this beneficial effect when given in 250-500 mg doses. When levonorgestrel was used in doses as low as 30 micrograms daily, there was no change in cholesterol levels over a period of 6 mth, suggesting that the adverse effect of the androgenic type progestogens is dose-related and is probably only significant when extremely high dosages are administered.

Cholesterol↗
PubMed2004

Facile synthesis of 4-substituted-4-aminopiperidine derivatives, the key building block of piperazine-based CCR5 antagonists.

4-Substituted-4-aminopiperidine is an interesting structural motif found in a number of bioactive compounds. An efficient and convenient method for the synthesis of 4-differently substituted-4-aminopiperidine derivatives was described, employing isonipecotate as a starting material and Curtius rearrangement as a key step. The alkylation of isonipecotate could introduce various substituents at the 4-position of the piperidine ring. With this key building block, we are able to efficiently synthesize piperazino-piperidine based CCR5 antagonist in a highly convergent manner free of using toxic reagents such as diethylaluminum cyanide. The concise synthesis of a potent bioavailable CCR5 antagonist as HIV-1 entry inhibitor, Sch-350634 (1) was accomplished in excellent yield using N'-Boc-4-methyl-4-aminopiperidine 5a as a smart building block. The new methodology provides a facile and practical access to the piperazino-piperidine amide analogs as HIV-1 entry inhibitors.

Alkylation↗
PubMed2004

Identification of 4-piperazin-1-yl-quinazoline template based aryl and benzyl thioureas as potent, selective, and orally bioavailable inhibitors of platelet-derived growth factor (PDGF) receptor.

4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives such as 14 (CT53986) have been identified to be potent and selective inhibitors of the phosphorylation of PDGFR. SAR-investigations are described in the arylamine segment, C-7 appendage, and the thiourea moiety. Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity. PK profiles of the optimized compounds in rat, dog, and cynomolgus monkey are described.

Administration, Oral↗
PubMed2005

Synthesis of isonicotinic acid N'-arylidene-N-[2-oxo-2-(4-aryl-piperazin-1-yl)-ethyl]-hydrazides as antituberculosis agents.

A new series of antituberculosis agents 6-9 was designed, synthesized and evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv and clinical isolates in an agar dilution method. Compound 9h showed comparable in vitro activity (MIC) to isoniazid against M. tuberculosis H37Rv and clinical isolates (sensitive strains) and superior activity against resistant strains of M. tuberculosis.

Antitubercular Agents↗
PubMed2006

Dithiocarbamic acid esters as anticancer agent. Part 1: 4-substituted-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl esters.

A variety of 4-N atom substituted derivatives were synthesized and evaluated for their in vitro anticancer activities using 4-methylpiperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl ester 4 as lead compound. Among them, compound 6a without any substituent on 4-N atom (R(1) = H) was found to be the most active anticancer agent with IC(50) = 5.3 microM against HL-60 and IC(50) = 11.5 microM against Bel-7402, respectively. Increase in the polarity and/or introduction of suitable acyl groups at the 4-N atom of the lead compound 4 are favorable for the improvement of activity.

Antineoplastic Agents↗
PubMed2004

The metabolism of the piperazine-type phenothiazine neuroleptic perazine by the human cytochrome P-450 isoenzymes.

Identification of cytochrome P-450 isoenzymes (CYPs) involved in perazine 5-sulphoxidation and N-demethylation was carried out using human liver microsomes and cDNA-expressed human CYPs (Supersomes). In human liver microsomes, the formation of perazine metabolites correlated significantly with the level of CYP1A2 and ethoxyrezorufin O-deethylase activity, as well as with the level of CYP3A4 and cyclosporin A oxidase activity. Moreover, the formation of N-desmethylperazine also correlated well with S-mephenytoin 4'-hydroxylase activity (CYP2C19). alpha-Naphthoflavone (a CYP1A2 inhibitor) and ketoconazole (a CYP3A4 inhibitor) significantly decreased the rate of perazine 5-sulphoxidation, while ticlopidine (a CYP2C19 inhibitor) strongly reduced the rate of perazine N-demethylation in human liver microsomes. The cDNA-expressed human CYPs generated different amounts of perazine metabolites, but the preference of CYP isoforms to catalyze perazine metabolism was as follows (pmol of product/pmol of CYP isoform/min): 1A1>2D6>2C19>1A2>2B6>2E1>2A6 approximately 3A4>2C9 for 5-sulphoxidation and 2C19>2D6>1A1>1A2>2B6>3A4>2C9>2A6 for N-demethylation. In the light of the obtained results and regarding the contribution of each isoform to the total amount of CYP in human liver, it is concluded that CYP1A2 and CYP3A4 are the main isoenzymes catalyzing 5-sulphoxidation (32% and 30%, respectively), while CYP2C19 is the main isoform catalyzing perazine N-demethylation (68%). CYP2C9, CYP2E1 CYP2C19 and CYP2D6 are engaged to a lesser degree in 5-sulphoxidation, while CYP1A2, CYP3A4 and CYP2D6 in perazine N-demethylation (6-10%, depending on the isoform).

Adult↗