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At least 73 records · Page 4Linked to original sources
PubMed2002

Synthesis and antitumor activity of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)propane]dichloroplatinum(II) complexes.

Enantiomerically pure 1, 2-diamino-1-(4-fluorophenyl)propanes were synthesized by stereospecific and stereoselective procedures by use of the (1R, 2S)- and (1S, 2R)-2-amino-1-(4-fluorophenyl)propanols (12a) as intermediates. The enantiomeric purity was determined by (1)H NMR spectroscopy after conversion of the propanolamines and the diamines with (1R)-myrtenal into mono- and diimines. For the coordination to platinum the diamines were reacted with K(2)PtCl(4). The resulting dichloroplatinum(II) complexes 4F-Ph/Me-PtCl(2) were tested for antiproliferative activity on the MCF-7 breast cancer cell line. (SS)- and (RR)-4F-Ph/Me-PtCl(2) produced the strongest inhibitory effect. Both complexes showed cytocidal effects, (SS)-4F-Ph/Me-PtCl(2) even in a concentration of 1 microM. The (1S, 2R)- and (1R, 2S)-configurated complexes were far less active (SS > RR > RS = SR) and comparable in this respect with the standard cisplatin.

Antineoplastic Agents↗
PubMed1996

The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations.

Studies were conducted in healthy male volunteers (n = 171; age range, 19-49 years; 22-27 subjects per study) to examine the following: pharmacokinetics and dose proportionality of the antihistamine clemastine; the effect of coadministration of phenylpropanolamine and clemastine on the pharmacokinetics of the two drugs; and the bioavailability of clemastine tablets and combination tablets of clemastine and sustained-release phenyl-propanolamine under fasted and fed conditions after single-dose administration and at steady state. All studies used crossover designs, with randomized drug treatments separated by a 7-day washout period for the single-dose studies, and with administration every 6 or 12 hours for 7 days per treatment for the steady-state studies. After single oral doses of clemastine solution (1,2, and 4 mg), the area under the concentration-time curve (AUC) and maximum concentration (Cmax) were dose proportional. Clemastine showed a first-pass reduction in the extent of absorption, with oral bioavailability calculated as 39.2 +/- 12.4%. Extravascular distribution of drug was suggested by the high volume of distribution (799 +/- 315 L) and low Cmax (0.577 +/- 0.252 ng/mL/mg) observed at 4.77 +/- 2.26 hours after administration, and by the biphasic decline in plasma concentration. The terminal elimination half-life (t1/2) of clemastine was 21.3 +/- 11.6 hours. Steady-state concentrations of clemastine were consistent with linear pharmacokinetic processes, and clearance was unaffected by age in the range studied, or by race. Clemastine solution and tablets were bioequivalent, and food had no significant effect on rate and extent of absorption of clemastine. The 1- and 2-mg clemastine tablets showed proportional bioavailability. Coadministration of clemastine with phenylpropanolamine did not significantly influence the pharmacokinetics of clemastine or the AUC and elimination t1/2 of phenylpropanolamine, but reduced the rate of absorption of phenylpropanolamine. Combination tablets containing 1 mg or 2 mg of immediate-release clemastine plus 75 mg of sustained-release phenylpropanolamine for twice daily administration were bioequivalent to the separate components and showed no significant interaction with food.

Adult↗
PubMed2004

Physicochemical and crystallographic characterization of mefenamic acid complexes with alkanolamines.

The preparation of mefenamic acid (MH)-alkanolamine (propanolamine, diethanolamine, triethanolamine) complexes was attempted to increase the transdermal flux of MH. Differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray crystallographic studies demonstrated that MH and each alkanolamine formed an ion pair complex. The series of amine complexes had a lower melting point and higher solubility in water compared with pure MH.

Alkanes↗
PubMed1985

Anticonvulsant properties of phencyclidine-like drugs in mice.

Primarily on the basis of activity in [3H]phencyclidine (PCP) binding assays and drug discrimination studies, a number of structurally dissimilar compounds have been found to be PCP-like. Drugs from four of these classes of PCP-like compounds were examined for anticonvulsant activity in the pentylenetetrazol (PTZ) seizure test. Male albino mice, eight per dose, were administered the drug or vehicle i.p. 10 min before PTZ (125 mg/kg s.c.). At each dose, the number of subjects and latency to clonic and/or tonic seizures within 15 min following PTZ were recorded. The anticonvulsant properties of PCP, ketamine, (+)-N-allylnormetazocine, etoxadrol, dexoxadrol and (-)-2-methyl-3,3-diphenyl-3-propanolamine ((-)-2-MDP) were selective for tonic seizures. The highest dose tested for each compound completely prevented the occurrence of tonic seizures. Levoxadrol and (+)-2-MDP, drugs devoid of PCP-like activity in other tests, were also inactive in the PTZ seizure test. These results demonstrate that similarities among PCP-like drugs previously shown using binding assays and drug discrimination procedures can be extended to include anticonvulsant effects, and they suggest common cellular sites of action for these properties.

Animals↗
PubMedDate not supplied

Pharmacokinetic studies using multiple administration of RO 03-8799, a 2-nitroimidazole radiosensitizer.

It has been shown that the propanolamine 2-nitroimidazole Ro 03-8799, is about an order of magnitude more efficient than misonidazole as a radiosensitizer in vitro, which is more than its electron affinity would predict. However, in vivo studies have so far shown only a minimal improvement compared to misonidazole. One reason for this could be that diffusion to the site of action in the hypoxic cell is restricted by the short half-life in the mouse and the net positive charge carried by the drug at physiological pH. Ways of maintaining a constant blood or tumor concentration over a period of 1--2 hours were investigated so that the tumor response could be assessed after this time. Initial experiments used multiple intraperitoneal or intravenous injections, for which the amount of drug required can be calculated theoretically provided sufficient pharmacokinetic data are available. Later experiments using continuous infusion of the drug were aimed at maintaining the gross tumor concentration equal to that found at the time of peak sensitization following a single administration. Results will be presented using each of these approaches. The technical feasibility and advantages of each method, together with general problems associated with interpreting any radiobiological results obtained using this approach will be discussed.

Animals↗
PubMed2006

Synthesis and antitubercular activity of substituted phenylmethyl- and pyridylmethyl amines.

A total of 42 benzyl- and pyridylmethyl amines were synthesized either by reductive amination of aromatic/heteroaromatic aldehydes with amines or by conjugate addition of amines to the cinnamates followed by reduction of the ester group with lithium aluminium hydride to the respective propanolamines. All the synthesized compounds were evaluated against both avirulent and virulent strains of Mycobacterium tuberculosis. Many of the compounds exhibited MIC as low as 1.56microg/mL. Few of potent compounds were also evaluated against clinical isolates of MDR TB and found to be active at one or other concentrations with MIC as low as 3.12microg/mL.

Amines↗
PubMed2004

The selective utilization of substrates in vivo by the phosphatidylethanolamine and phosphatidylcholine biosynthetic enzymes Ept1p and Cpt1p in yeast.

In yeast, the aminoalcohol phosphotransferases Ept1p and Cpt1p catalyze the final steps in the CDP-ethanolamine and CDP-choline routes leading to phosphatidylethanolamine (PE) and phosphatidylcholine (PC), respectively. To determine how these enzymes contribute to the molecular species profiles of PE and PC in vivo, wild-type, cpt1Delta, and ept1Delta cells were pulse labeled with deuterated ethanolamine and choline. Analysis of newly synthesized PE and PC using electrospray ionization tandem mass spectrometry revealed that PE and PC produced by Ept1p and Cpt1p have different species compositions, demonstrating that the enzymes consume distinct sets of diacylglycerol species in vivo. Using the characteristic phospholipid species profiles produced by Ept1p and Cpt1p as molecular fingerprints, it was also shown that in vivo CDP-monomethylethanolamine is preferentially used as substrate by Ept1p, whereas CDP-dimethylethanolamine and CDP-propanolamine are converted by Cpt1p.

Diacylglycerol Cholinephosphotransferase↗
PubMed2000

High-speed recovery of germanium in a convection-aided mode using functional porous hollow-fiber membranes.

A porous hollow-fiber membrane capable of recovery of germanium from a liquid stream was prepared by radiation-induced graft polymerization of an epoxy-group-containing vinyl monomer, glycidyl methacrylate, and subsequent functionalization with 2,2'-iminodiethanol, di-2-propanolamine, N-methylglucamine, and 3-amino-1,2-propanediol. The functional group density was as high as 1.4 mol per kg of the resultant hollow fiber. The polymer chains containing functional groups surrounding the pores enabled a high-speed recovery of germanium during permeation of a germanium oxide (GeO2) solution through the pores of the hollow fiber. Because of a negligible diffusional mass-transfer resistance, germanium concentration changes with the effluent volume, i.e., breakthrough curves, overlapped irrespective of the residence time of the solution, which ranged from 0.37 to 3.7 s across the hollow fiber. After repeated use of adsorption and elution, the adsorption capacity did not deteriorate.

Chromatography↗
PubMed1999

beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines.

To further explore the structure-activity relationships of beta-adrenoceptor (beta-AR) antagonists, a series of 25 para-substituted N-isopropylphenoxy-propanolamines were synthesised, nine of which are new compounds. All have been examined for their ability to antagonise beta(1)-ARs in rat atria and beta(2)-ARs in rat trachea. Substitution in the para-position of the phenyl ring is thought to confer beta(3)-specificity and the selectivity of these compounds for the beta(1)-AR ranges from 1.5-234. None of the compounds tested were selective for the beta(2)-AR. Of the 25 compounds studied, 22 had reasonable (pA(2) > 7) potencies for the rat beta(1)-AR. Only compound 1 displayed reasonable (pA(2) > 7) potency for the rat beta(2)-AR. Twenty two compounds were used as the training set for comparative molecular field analysis (CoMFA) of antagonist potency (pA(2)) at the rat beta(1)- and beta(2)-ARs. The inclusion of a number of additional physical characteristics improved the QSAR analysis over models derived solely using the CoMFA electrostatic and steric fields. The final models predicted the beta(1)- and beta(2)-AR potency of the compounds in the training set with high accuracy (r(2) = 0.93 and 0.86 respectively). The final beta(1)-AR model predicted the beta(1)-potencies of two out of the three test compounds, not included in the training set, with residual pA(2) values < -0.14, whereas the test compounds were not as well predicted by our final beta(2)-AR model (residual pA(2) values < -0.38).

Journal Article↗
PubMed2002

Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells.

A variety of anti-cancer drugs elevate endogenous ceramide, thereby inducing apoptosis in tumor cells. Recently, we have introduced novel ceramide analogs of the beta-hydroxy alkyl amide type, which trigger pro-apoptotic signaling pathways without prior elevation of endogenous ceramide. They induce apoptosis specifically in rapidly dividing neuroblastoma cells, but not in resting or differentiated cells. We characterize new ceramide mimics that have been derived from N-acylation of serinol (S), diethanolamine (B), propanolamine (P), and tris(hydroxy-methyl)methylamine (T) with myristic (14), palmitic (16), or oleic (18) acid. The water solubility of these compounds exceeds that of ceramide by more than 100-fold (up to 5 mM). Apoptosis of human neuroblastoma, glioma, medulloblastoma, and adenocarcinoma cells is induced by N-(2-hydroxy-1-(hydroxymethyl)ethyl)-palmitoylamide, C16-serinol (S16), N-(2-hydroxy-1-(hydroxymethyl)ethyl)-oleoylamide, C18-serinol (S18), N-bis(2-hydroxyethyl)-myristoyl-amide (B16), and N-tris(hydroxymethyl)methyl-oleoylamide (T18) within 60 min of incubation, and is completed even after removal of the compound from the medium. This is most likely due to a rapid uptake of the analogs followed by their slow release from the cells. Alteration of the acyl chain length to less than 14 methylene units, removal of the amino group, or reducing the number of hydroxyalkyl residues to less than two significantly lowers or eliminates the pro-apoptotic potential of these compounds. The target specificity of novel ceramide analogs for tumor cells, their water solubility, and fast pro-apoptotic mechanism indicates a high therapeutic potential for cancer treatment.

Apoptosis↗
PubMed2000

Simultaneous estimation of phenylpropanolamine HCl, guaiphenesin and diphenylpyraline HCl in syrups by LC.

A simple, precise and accurate HPLC method was developed for the simultaneous estimation of phenyl-propanolamine HCl, guaiphenesin and diphenylpyraline HCl in syrup. The method was carried out on a Shimpak C8 column with a mobile phase consisting of acetonitrile-triethylamine (pH adjusted to 3.5 using orthophosphoric acid; 0.5%), (35:65, v/v) at a flow rate of 1.2 ml min(-1). Detection was carried out at 210 nm. Diphenhydramine was used as internal standard. The validation of the method was also carried out.

Chromatography, High Pressure Liquid↗
PubMed1998

Synthesis and pharmacological activity of the stereoisomers of GP-88, a propafenone-type modulator of multidrug resistance.

All four stereoisomers of the propafenone-type MDR-modulator GP-88 (1) were synthesized using a combined approach with chiral pool building blocks and an acetalic protective group, which allows not only diastereoseparation but also assignment of absolute configuration via NMR spectroscopy. Those isomers with different configuration on the center of chirality in the propanolamine side chain showed statistically different PGP-inhibitory activity. Generally, the (R)-configured isomers were by a factor of nearby two higher active than the (S)-isomers. No differences in activity were observed for isomers with different configuration on the benzylic center of chirality.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Aminophospholipid translocase of human erythrocytes: phospholipid substrate specificity and effect of cholesterol.

The outside-inside translocation rate and transmembrane equilibrium distribution, at 37 degrees C, of 16 different amphiphilic spin-labeled phospholipids have been determined in human erythrocytes. The transmembrane distribution was assessed by bovine serum albumin extraction of the spin-labels present in the outer monolayer. Within 15 min, more than 90% of the phosphatidylserine analogue was found in the inner monolayer; the equilibrium distribution of phosphatidylethanolamine spin-label was approximately 85-90% inside, with a half-time for translocation of approximately 50 min. In contrast, phosphatidylcholine reached a distribution corresponding to approximately 30% of the labels inside with a half-time of approximately 8 h, and only traces of sphingomyelin were found in the inner monolayer after 16 h. Thus, the spin-label analogues distributed themselves like endogenous phospholipids in red cells with a spontaneous segregation between the amino lipids and the choline-containing phospholipids. Progressive methylation of the amine group of phosphatidylethanolamine resulted in a stepwise decrease of the specific transport; modification of the beta-carbon of the serine also decreased the efficiency of the rapid translocation without abolishing it. Phosphatidyl-propanolamine was not transported. Substitution of the glyceride group by a ceramide abolished the rapid outside-inside translocation even with a molecule bearing a serine head group. Also it was found that esterification of the sn-2 position of the glycerol component was necessary for a rapid translocation since lysophosphatidylserine was only slowly transported from outside to inside.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1995

Synthesis, pharmacologic activity, and structure-activity relationships of a series of propafenone-related modulators of multidrug resistance.

A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model. Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well as the substitution pattern at the nitrogen atom is crucial for activity of the compounds. Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity. Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.

Daunorubicin↗
PubMed1992

Flavones. 3. Synthesis, biological activities, and conformational analysis of isoflavone derivatives and related compounds.

A series of 2-alkylisoflavone derivatives 1 was prepared with the intent to study the importance of the phenyl group (at the 3-position) of the isoflavone in imparting antihypertensive activity and the substitution effects at the 2-position of isoflavone. With the exception of the 2-isopropyl analog, the antihypertensive activity of these compounds appears to have a slow onset and long duration. None of the analogs appears better than the corresponding flavone (3) and 3-phenylflavone (2) analogs. An unsuccessful attempt to correlate the relationship between antihypertensive activity and the calculated torsional angle of C2-C3-C1'-C2' is discussed. Antiinflammatory activities of these compounds along with 7-(oxypropylamine)flavones were also evaluated and found to be not very potent. The antiinflammatory activity appears to be sensitive to steric effects of the alkyl group on the nitrogen and of substituents at the 2-position of the isoflavones, while the hydroxyl group of the propanolamine side chain is not essential.

Animals↗
PubMed1991

Synthesis and ocular antihypertensive activity of new imidazolidine derivatives containing a beta-blocking side chain.

The syntheses of new phenylimidazolidine derivatives (3-6)1 containing a propanolamine oxime or an oxypropanolamine moiety attached either to the aromatic or to the imidazolidine ring are described. These compounds were evaluated for potential ocular antihypertensive activity in alpha-chymotrypsin-induced ocular hypertension in rabbits. These compounds represent a unique series of effective ocular antihypertensive agents that despite possessing structural characteristics of beta-blockers and of imidazolidine derivatives, exhibit weak alpha- and beta-adrenergic agonist and antagonist activities. These findings may be of significant therapeutic importance in the medical management of glaucoma.

Animals↗
PubMed1988

Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists.

The molecular electrostatic potential (MEP) of 32 beta-adrenoceptor ligands, mainly antagonists, was calculated by the STO-3G ab initio quantum mechanical method. The MEP of phenylethanolamines (PEAs) features a negative minimum in the meta region (designated M1) which is topographically equivalent to a minimum (designated M2) found in the vicinity of the aromatic ring in all (aryloxy)propanolamines (AOPAs). In these compounds, a second negative zone located beyond the meta position and designated M3 is found in all beta 1-selective antagonists and in some nonselective and beta 2-selective antagonists. The beta 1-selective antagonists feature in the para position an additional zone which is positive (P4) in the full antagonists and negative (M4) in the antagonists displaying intrinsic sympathomimetic activity (ISA). The MEP-based pharmacophoric models of PEAs, AOPAs, and oxime ethers show common elements and lead to a proposed general model for beta-adrenoceptor ligands.

Adrenergic beta-Agonists↗
PubMed1988

Synthesis and beta-adrenergic antagonism of 2-(aryloxy)-1-(2-piperidyl)ethanols.

A series of erythro- and threo-2-(aryloxy)-1-(2-piperidyl)ethanol derivatives (3) was synthesized from 2-(2-oxiranyl)pyridine for evaluation as beta-antagonists. Most compounds displayed high competitive beta-blocking potency, but they lacked significant beta 1/beta 2 selectivity. The 1-naphthoxy derivative erythro-3b was 17 (beta 1) and 33 (beta 2) times more potent than its open-chain analogue, propranolol. Within the whole series, erythro-3 diastereomers were more potent beta-blockers than the threo-3 isomers, and the potency of the latter seems to be rather insensitive to structural modification. The effect of N-methylation and of interposition of an alkyl chain between the aromatic ring and the side chain, while being detrimental to beta-blocking activity, was less marked than in the classic (aryloxy)propanolamine blockers.

Adrenergic beta-Antagonists↗