Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PIPERIDINES”

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 901 records · Page 50Linked to original sources
PubMed2003

Synthesis and repellent efficacy of a new chiral piperidine analog: comparison with Deet and Bayrepel activity in human-volunteer laboratory assays against Aedes aegypti and Anopheles stephensi.

Optically active (1S,2'S)-2-methylpiperidinyl-3-cyclohexen-1-carboxamide (SS220) is a new synthetic arthropod repellent. A three-step synthesis based on a chiral Diels-Alder reaction and diastereomeric resolution of 2-methylpiperidine was developed to prepare the compound. Quantitative laboratory assays using human volunteers compared the effectiveness of SS220 with the commonly used repellents Deet and Bayrepel against Aedes aegypti (Linnaeus) and Anopheles stephensi Liston mosquitoes. In two experiments using Aedes aegypti, one using a single identical dose and one with varying doses used to develop a dose-response curve, SS220 was as effective as Deet and both compounds were more effective than Bayrepel. The three compounds were equally effective against An. stephensi. Based on the ease of its synthetic preparation and its repellent efficacy, we surmise that SS220 is a candidate to serve as a new and effective alternate repellent for protection against arthropod disease vectors.

Aedes↗
PubMed2005

Influence of trishomocubanes on sigma receptor binding of N-(1-benzyl-piperidin-4-yl)-4-[123I]iodobenzamide in vivo in the rat brain.

Three new trishomocubane analogues based on the 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)] dodecane-3-ol skeleton have been synthesised and assessed for their affinities at both sigma-1 and sigma-2 receptors. The effect of various N-substitution on the polycyclic moiety was examined. All synthesised compounds displayed high affinity for sigma-1 receptors (9-10 nM) and good affinity for sigma-2 receptors (230-310 nM), suggesting that substitution at the nitrogen moiety of the trishomocubane is well tolerated and represents a platform for the development of improved higher affinity sigma receptor ligands. The interaction of these functionalised trishomocubanes on the binding of the known sigma receptor radioligand, 4-[123I]IBP, was evaluated in the rat brain. Although 4-[123I]IBP had been used for imaging sigma receptors in tumours, this is the first examination of sigma receptor binding in the rat brain and therefore the potential of 4-[123I]IBP for imaging the brain was also evaluated. In vivo specificity and selectivity of 4-[123I]IBP binding was examined by studying the effects of pre-administration of sigma receptor binding drugs (+)-pentazocine and unlabelled 4-IBP. This resulted in a blockade of only 42% of 4-[123I]IBP uptake in the brain indicating high degree of non-specific binding suggesting that it may not be suitable for imaging sigma receptors in the brain. The inhibition of 4-[123I]IBP uptake using the two of the three trishomocubanes displayed a consistent blockade of 48-30% in all brain structures. This demonstrates for the first time the ability of functionalised trishomocubanes to interact with sigma receptors in vivo.

Animals↗
PubMed1991

Comparison of coupling subsites and inhibition effects of piperidine alkaloids and aminoketones on plant amine oxidases.

In the present work we compare the binding subsites of inhibitors from a series of alkaloids and aminoketones on pea and sainfoin diamine oxidase (EC 1.4.3.6; DAO) by the graphical method. As standard competitive inhibitors we have chosen oxoanalogs of the substrates, namely, 1,4-diamino-2-butanone and 1,5-diamino-3-pentanone, which were compared with the alkaloids (+)-sedamine, (-)-norallosedamine, (-)-norsedamine, L-lobeline, cinchonine and aromatic analogs of aliphatic aminoketones such as 1-amino-3-phenyl-3-propanone and 1-amino-3-phenyl-2-propanone. In the case of pea DAO all inhibitors compete for the same subsites with 1,4-diamino-2-butanone and 1,5-diamino-3-pentanone (alpha = infinity). In the case of sainfoin enzyme they are bound to other subsites and the interaction constants (0 < alpha < 1) point to a positive attraction between these two types of inhibitors. With sainfoin DAO, 1-amino-3-phenyl-3-propanone is bound into the same subsite as 1,4-diamino-2-butanone. Cinchonine and 1-amino-3-phenyl-3-propanone are bound to two different subsites and the value of the interaction constant (1 < alpha < infinity) shows repulsion between the inhibitors.

Alkaloids↗
PubMed1990

Multiple congenital contractures (MCC) and cleft palate induced in goats by ingestion of piperidine alkaloid-containing plants: reduction in fetal movement as the probable cause.

Fetal movement, observed by ultrasound imaging, was significantly reduced (P less than or equal to 0.001) in pregnant goats gavaged with Conium seed and Nicotiana glauca and temporarily reduced with fresh Conium plant. Conium seed and Nicotiana glauca induced cleft palate and multiple congenital contractures in 100% of the kids born to pregnant goats gavaged with these plants. Multiple congenital contractures included torticollis, scoliosis, lordosis, arthrogryposis, rib cage anomalies, over extension, and flexure and rigidity of the joints. However, in goats gavaged with fresh Conium plant, fetal movement was inhibited for only about 5 hours after each individual dosage and gradually returned to control levels 12 hours after dosing. Fetal malformations in this group were limited from modest to moderate contractures of the front limbs, which resolved by 8-10 weeks post partum. No cleft palates were induced. Fetal movement was not inhibited in goats fed Lupinus caudatus and no cleft palates or multiple congenital contractures were induced in their offspring. The duration of the reduction in fetal movement appears to be an important factor in the severity and permanence of the deformities, particularly with cleft palate, spinal column defects, and severe joint deviation and fixation.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Evidence for peroxidative oxidation of substituted piperidine nitroxides, acting as apoptosis inducers in Yoshida Sarcoma cells in vivo.

The results presented herein clearly indicate that nitroxide derivatives--free radicals are effective as substrates for one-electron oxidation in the peroxidase cycle involving hydrogen peroxide, which have been the subject of considerable controversy. This oxidation is catalyzed enzymatically and it might occur in tumor cells (in vivo) where the level of ROS (H2O2 and O2.-) is increased. The result of this reaction involving hydrogen peroxide is the obligative formation of the oxo-ammonium cation involved in the superoxide dismutase-mimic reaction of nitroxides with superoxide and/or in reaction with H2O2 leading to superoxide formation and regeneration of the parent nitroxide molecule. The efficiency of this enzymatically catalyzed oxidation of nitroxide(s) depends on the structure of the substituent in position 4 of nitroxide ring as follows: -OCH3 > -NHCOCH3 > -NHCOCH2CH3. Notably, the reduced nitroxide salt was not substrate for peroxidatic oxidation clearly indicating the importance of the free radical moiety of the nitroxide molecule. These findings may have some relevance in the recent investigations of antioxidant properties/mechanisms of nitroxides. Based on these considerations we hypothesize that the administration of oxidizable free radical nitroxide compounds--antioxidants may be a useful strategy in the treatment and investigations of cancer diseases. An in vivo study ("Screening test of chemicals employing Yoshida Sarcoma animals") was carried out to verify whether the structure and/or the chain length of substituent of oxidizable nitroxide derivatives--antioxidants could influence their apoptotic activity. The results reported in this study are encouraging as we found a limited correlation between the molecular oxidative properties of nitroxides under study, their structure and antitumor (apoptotic) action. In conclusion, this work demonstrates that investigation of the structure-dependent oxidation of antioxidatively acting nitroxides can become a very important step in their future screening and selection for applications in vivo and in vitro.

Animals↗
PubMed1975

Tumor initiation by N-acyloxy derivatives of piperidine and N-arylacetamides.

Four N-Acetoxy-N-arylacetamides previously found to be local sarcomagens in the rat have been found to be initiators of tumorigenesis in mouse skin. The order of activity was: N-acetoxy-2-acetamidophenanthrene greater than N-acetoxy-4-acetamino-stilbene similar to N-acetoxy-2-acetamido-fluorene greater than N-acetoxy-4-acetamidobiphenyl. Two substituted N-benzoyloxypiperidines previously shown to yield nitrenium ions on solvolysis in methanol also had initiating activity in mouse skin.

Acetamides↗
PubMed2001

A new antiestrogen, 2-(4-hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol hydrochloride (ERA-923), inhibits the growth of tamoxifen-sensitive and -resistant tumors and is devoid of uterotropic effects in mice and rats.

PURPOSE: Tamoxifen is an antiestrogen used in women who have estrogen receptor (ER)-alpha-positive breast cancer. Unfortunately, resistance to tamoxifen is common in women with metastatic disease and side effects, including increased risk of endometrial cancer, exist. Here we describe the activity of a new selective ER modulator, ERA-923, in preclinical models focused on these limitations. EXPERIMENTAL DESIGN: The ability of ERA-923, 4-OH tamoxifen, or raloxifene to inhibit estrogen-stimulated growth was evaluated in cell-based and xenograft assays with tumor cells that are sensitive or resistant to tamoxifen. Uterine effects of selective ER modulators were compared in rodents. RESULTS: ERA-923 potently inhibits estrogen binding to ER-alpha (IC(50), 14 nM). In ER-alpha-positive human MCF-7 breast carcinoma cells, ERA-923 inhibits estrogen-stimulated growth (IC(50), 0.2 nM) associated with cytostasis. In vitro, a MCF-7 variant with inherent resistance to tamoxifen (10-fold) or 4-OH tamoxifen (>1000-fold) retains complete sensitivity to ERA-923. Partial sensitivity to ERA-923 exists in MCF-7 variants that have acquired profound tamoxifen resistance. In tumor-bearing animals, ERA-923 (10 mg/kg/day given p.o.) inhibits 17beta-estradiol-stimulated growth in human tumors derived from MCF-7, EnCa-101 endometrial, or BG-1 ovarian carcinoma cells, including a MCF-7-variant that is inherently resistant to tamoxifen. Raloxifene is inactive in the MCF-7 xenograft model. Unlike tamoxifen, droloxifene, or raloxifene, ERA-923 is not uterotropic in immature rats or ovariectomized mice. Consistent with this, tamoxifen, but not ERA-923, stimulates the growth of EnCa-101 tumors. CONCLUSIONS: In preclinical models, ERA-923 has an improved efficacy and safety compared with tamoxifen. Clinical trials with ERA-923 are in progress.

Animals↗
PubMed2001

Piperidine-containing histamine H3-receptor antagonists of the carbamate series: variation of the spacer length.

Ten carbamate derivatives have been prepared from appropriate isocyanates and omega-piperidino-1-alkanols. All compounds belong to the new generation of non-imidazole histamine H3-receptor ligands which may have beneficial pharmacokinetic properties compared with the classical imidazole-containing H3-receptor antagonists. The carbamates were evaluated in vitro for antagonist activity at guinea-pig (gp) H3, H2, H1, and M3 receptors, respectively. They displayed moderate affinity for H3 receptors (pA2 5.8-7.0 in the gp ileum assay) as well as low to moderate selectivities vis-à-vis H2 (gp atrium), H1 (gp ileum), and M3 (gp ileum) receptors. A typical member of this series is 7-piperidino-1-heptyl N-(4-phenyl-1-butyl)carbamate (17) with pA2 values of 7.02 (H3), 5.92 (H1), and 6.38 (M3), respectively, and a pD'2 value of 5.46 (H2).

Animals↗