bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of Suramin in Aqueous Solution; Possible Implications for the Search for Suramin Metabolites in Patients
Authors: Kassack Matthias , Nickel Peter 
Published: October 2006

AbstractThe stability of an aqueous solution of suramin has been determined. The only degradation product detectable by HPLC was the amine precursor 2. The decomposition kinetics of suramin at different temperatures are shown. Because of first order kinetics the Arrhenius equation could be used to evaluate the decomposition data. A good correlation was obtained between the reaction constants and the temperature (r = 0.9898). After 42 days at 37 °C, 2% of suramin are hydrolysed. Possible implications of our results for the search for suramin metabolites in patients are discussed.
Non‐Steroidal Anti‐Inflammatory Agents, Part 20 [1] Method for Testing Non‐Steroidal Anti‐Inflammatories: The Modified Hen's Egg Chorioallantoic Membrane Test (HET‐CAM Test) Compared to Other Procedures
Authors: Dannhardt Gerd , Kreher Mareta , Nowe Ulrike , Pies Andreas 
Published: October 2006

AbstractThe delay of onset of irritation phenomena at the chorioallantoic membrane of incubated hen's eggs, a parameter for anti‐inflammatory activity, was determined for the pharmaceutical substances diclofenac, flufenamic acid, ibuprofen, indomethacin, ketoprofen, piroxicam, phenylbutazone, salicylic acid, and sodium salicylate. Alongside questions relating to the dose‐effect ratio, metabolisation, recovery, and diffusion of the substances to their site of action were investigated. The reproducibility of the procedure and its selectivity with regard to substances with a different mechanism of action is proven. The method allows classification of the substances according to their anti‐inflammatory potency. However, correlation with the results of enzyme inhibition or in vivo results is only possible to a limited extent.
Synthesis and Pharmacological Studies of 3‐Amino‐2‐methyl‐1‐phenylpropanones as Hypolipidemic Agents in Rodents
Authors: Huang Yunsheng , Hall Iris H. 
Published: October 2006

AbstractA series of 3‐amino‐2‐methyl‐1‐phenylpropanones were synthesized and proven to have potent hypolipidemic activity in rodents by lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day, i.p. and orally. Many of these analogs showed significantly higher activity than standard drugs, lovastatin and clofibrate at their therapeutic doses. 2‐Methyl‐3‐(perhydroazepin‐1‐yl)‐1‐phenylpropanone (@!4), 3‐(4‐methylpiperazin‐1‐yl)‐1‐phenylpropanone (5), and 2‐methyl‐3‐(4‐pyrrolidinocarbonyl‐methylpiperazin‐1‐yl)‐1‐(4‐fluorophenyl) propanone (17) showed the best overall activities in lowering both serum cholesterol and triglyceride levels in CF1 mice at 8 mg/kg/day after 16 days of treatment. Compounds 4, 5, and 17 lowered serum cholesterol levels 63%, 58%, and 42%, respectively, after 16 days at 8 mg/kg/day i.p. These agents reduced the serum triglyceride levels by 33%, 37%, and 54%, respectively. In Sprague‐Dawley rats these compounds also demonstrated significant serum lipid lowering effects by decreasing both serum cholesterol and triglyceride levels after 14 days of oral drug administration at 8 mg/kg/day. Compound 17 reduced the rat aorta cholesterol levels by 37%, triglyceride levels by 50%, and neutral lipid levels by 34% after 14 days of oral administration. These compounds lowered the chylomicron, VLDL, and LDL cholesterol and triglyceride levels while elevating the HDL cholesterol levels significantly. In hyperlipidemic rodents, these analogs also demonstrated significant serum lipid lowering effects but were less active than in normalipidemic rodents. The activities of some enzymes, such as mouse hepatic acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and hepatic lipoprotein lipase, were significantly reduced by these compounds.
Synthesis and Calcium Antagonistic Activity of 8‐[N‐[2‐(3,4‐Dimethoxyphenyl)ethyl]‐β‐alanyl]‐5,6,7,8‐tetrahydrothieno[3,2‐b][1,4]thiazepine Fumarate
Authors: Erker Thomas , Laimer Ingrid , Huck Sigismund , Boehm Stefan , Studenik Christian , Heistracher Peter 
Published: October 2006

AbstractKT‐362 is an antiarrhythmic and antihypertensive agent with vasodilating activity. Since it carries a homoveratryl group in the side chain, an obvious relation exists to the verapamil‐type calcium antagonists. Replacement of the fused aromatic moiety in KT‐362 with thiophene provided 8‐[N‐[2‐(3,4‐dimethoxyphenyl)ethyl]‐β‐analyl]‐5,6,7,8‐tetrahydrothieno[3,2‐b][1,4] thiazepine (1). Compound 1 shows a negative chronotropic activity in spontaneously beating right atria (IC50 = 23 μM, n = 7), and a negative inotropic effect in papillary muscles (IC50 = 2.7 μM, n = 7) and left atria (IC50 = 4 μM, n = 6) of the guinea‐pig heart. The decrease of contractility in papillary muscles could be antagonized by increasing the extracellular calcium concentration. Compound 1 was found to affect high (IC50: 70 ± 5 μM) and low (IC50: 129 ± 34 μM) voltage‐activated calcium channel currents as well as voltage‐activated sodium channel currents (IC50: 80 ± 13 μM) in chick dorsal root ganglion neurons. In addition, nicotine‐induced currents were potently inhibited (IC50: 6 ± 0.7 μM) in bovine chromaffin cells.
Phenylamino‐Pyrimidine (PAP) Derivatives: A New Class of Potent and Selective Inhibitors of Protein Kinase C (PKC)
Authors: Zimmermann Jürg , Caravatti Giorgio , Mett Helmut , Meyer Thomas , Müller Marcel , Lydon Nicholas B. , Fabbro Doriano 
Published: October 2006

AbstractPhenylamino‐pyrimidines represent a novel class of inhibitors of the protein kinase C with a high degree of selectivity versus other serine/threonine and tyrosine kinases. Steady state kinetic analysis of N‐(3‐[1‐imidazolyl]‐phenyl)‐4‐(3‐pyridyl)‐2‐pyrimidinamine (5), which showed potent inhibitory activity, revealed competitive kinetics relative to ATP. The adjacent H‐bond acceptor of the pyrimidine moiety next to an H‐bond donor of the phenylamine was found to be crucial for inhibitory activity. N‐(3‐Nitro‐phenyl)‐4‐(3‐pyridyl)‐2‐pyrimidinamine (7) preferentially inhibited PKC‐α (IC50 = 0.79 μM) and not the other subtypes tested. The inhibition constants of PKC‐α and the antiproliferative effect on T24 human bladder carcinoma cells showed a qualitative correlation, although with some exceptions.
Research on Antifungal and Antimycobacterial Agents. Synthesis and Activity of 4‐Alkylthiopyridine‐2‐carbothioamides
Authors: Klimešová Vera , Svoboda Martin , Waisser Karel , Machácek Miloš , Buchta Vladimír , Odlerová Želmíra 
Published: October 2006

AbstractA series of 4‐alkylthiopyridine‐2‐carbothioamides have been prepared and evaluated in vitro for antimicrobial activity. Chemical structures have been demonstrated by IR and 1H NMR data and by elemental analysis. The antimycobacterial activity of these compounds against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium, and Mycobacterium fortuitum, and the antifungal activity against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Trichophyton mentagrophytes, Aspergillus fumigatus, and Absidia corymbifera were determined by the MIC values. Compounds 3 exhibit good antimycobacterial activity compared to isoniazide. A moderate antifungal activity was observed against T. mentagrophytes. Activity is influenced by hydrophobicity of the alkyl group.
Structure‐Activity Relationship Studies of CNS Agents, Part 31[1]: Analogs of MP 3022 with a Different Number of Nitrogen Atoms in the Heteroaromatic Fragment — New 5‐HT1A Receptor Ligands
Authors: Paluchowska Maria H. , Dereń‐Wesońek Anna , Mokrosz (deceased) Jerzy L. , Charakchieva‐Minol Sijka , Chojnacka‐Wójcik Ewa 
Published: October 2006

AbstractTwo series of new MP 3022 analogs, i.e. 1‐(o‐methoxyphenyl)‐4‐n‐propylpiperazines (3, 4a, 4b, 6–9, and 12–13) and 2‐(n‐propyl)‐1,2,3,4‐tetrahydroisoquinolines (5a, 5b, 11a, and 11b) containing a terminal heteroaromatic system with a different number of nitrogen atoms, were synthesized and their 5‐HT1A/5‐HT2A and α1 receptor affinity was assayed. The majority of investigated piperazines may be classified as non‐selective 5‐HT1A/5‐HT2A/α1 receptor ligands. Compounds 3, 4a, 4b, 7–9a with the highest affinity for 5‐HT1A receptors (Ki = 4–54 nM) were tested in vivo. Their functional activity was differentiated; while 3, 8, and 9a behaved like weak antagonists of postsynaptic 5‐HT1A receptors, 4b and 7 may be classified as potential partial 5‐HT1A receptor agonists. Isomer 4a has characteristic features of a potential weak postsynaptic 5‐HT1A receptor agonist.
New NO‐Donors with Antithrombotic and Vasodilating Activities, Part 14 1,3,4‐Triazol‐1‐oles
Authors: Rehse Klaus , Piechocki Daniela , Schober Markus , Scheffler Heike , Reitner Nora , Unsöld E. 
Published: October 2006

AbstractFive 1,3,4‐triazol‐1‐oles (5a—f) with different alkyl, aryl, and arylalkyl substituents in 2,5‐position were synthesized and tested for their antithrombotic properties. The 2,5‐dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42 % in arterioles and by 33 % in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action.1,1′‐Azo‐bis‐ethanone oxime (7) — the synthetic precursor of 5a — inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 μmol/L.
Asymmetric Synthesis and Structure‐Activity Relationship of the Four Stereoisomers of the Antibiotic Amidinomycin Part 2: Microbiological Testing
Authors: Sung Sun‐Young , Kist Manfred , Frahm August W. 
Published: October 2006

AbstractThe stereoisomers of amidinomycin 7 and their intermediates 1–6, which are produced from homochiral 3‐oxocyclopentanecarboxylic acids by asymmetric synthesis, are tested for their antimicrobial effects by agar diffusion test and by Bouillon serial dilution assay. Their antibiotic activities against Bacillus subtilis, Staphylococcus aureus, and Micrococcus luteus, respectively, are reported. Structure‐activity relationships depend on the type and combination of functional groups, on only the relative stereochemistry as well as on the grade of lipophilia of the tested compounds.
Synthesis and Dopaminergic Properties of 3‐ and 4‐Substituted 1‐{2‐[5‐(1H‐Benzimidazole‐2‐thione)]ethyl}piperidines and Related Compounds
Authors: Dukic Sladjana , Kostic‐Rajacic Sladjana , Šoškic Vukic , Joksimovic Jelena 
Published: October 2006

AbstractWith an aim of creating new, high affinity dopaminergic ligands, six different 3‐ and 4‐substituted 1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}piperidines and nine related heterocyclic congeners were synthesized and evaluated for in vitro binding affinity at D1 and D2 dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4‐[bis‐(4‐fluorophenyl)methylene]‐piperidines, compounds 9e, 10d, and 11d, expressed moderate affinity for the D1 receptors, while all other compounds were inactive competitors of [3H]SCH 23390. Compounds 9c, 9d, 10c, 11a, and 11c were inactive in the D2 receptor binding assay, as well. Derivatives of 4‐phenylpiperidine (9–11b) and 3‐phenyl‐piperidine (10a) expressed a moderate to low affinity for the D2 receptors. However, racemic (±)‐1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}‐3‐phenylpiperidine 9a and its enantiomer (+)‐9a behaved as selective, high affinity D2 receptor ligands, the latter being some four times more active than the racemate.
Synthesis and Cytotoxic Action of 3,5‐Isoxazolidinediones and 2‐Isoxazolin‐5‐ones in Murine and Human Tumors
Authors: Hall Iris H. , Izydore Robert A. , Zhou Xaioming , Daniels Dwayne L. , Woodard Tyrone , Debnath Manik L. , Tse Elaine , Muhammad Rosallah A. 
Published: October 2006

AbstractThe 3,5‐isoxazolidinediones and 2‐isoxazolin‐5‐ones demonstrated potent cytotoxicity against the growth of human Tmolt3 T cell leukemia, murine P388 and L1210 leukemias, as well as human HeLa‐S3 uterine carcinoma and glioma tumor cell growth. The specificity of the 3,5‐isoxazolidinedione and 2‐isoxazoline‐5‐one derivatives as cytotoxic agents varied with the histological type of tumor cell. Selected compounds were active against solid HeLa uterine, KB nasopharynx, skin A431, SW‐480 adenocarcinoma, osteosarcoma and glioma growth. Selected compounds demonstrated in vivo antineoplastic activity against Ehrlich ascites carcinoma growth. In L‐1210 leukemia cells, the agents blocked DNA and protein synthesis at 25,50 and 100 μM over 60 min. The agents were effective in reducing rate limiting enzymes in the de novo purine and pyrimidine pathways. In addition they suppressed dihydrofolate reductase and ribonucleoside reductase activities with moderate inhibition of DNA and RNA polymerase activities. DNA itself was not a target of the agents.
Influence of Various Estrogens on Biotransformation: Affinity to Cytochrome P‐450, Structure Activity Relationships, and Scavenger Function
Authors: Gernhardt Sabine , Karge Elke , Schönecker Bruno , Klinger Wolfgang 
Published: October 2006

AbstractNine natural and synthetic estrogens, all derived from endogenous 17β‐estradiol, were tested for their affinity to cytochrome P‐450 (P450). Binding spectra of the estrogens with rat liver microsomal P450 and inhibition kinetics with characteristic monooxygenase model reactions (ethylmorphine N‐demethylation, EN, and ethoxycoumarin O‐deethylation, EO) were determined. In addition, uncoupling effects and/or free radical scavenger functions were analysed by NADPH/Fe++ stimulated microsomal luminol‐and lucigenin‐amplified chemiluminescense (CL). 17β‐Estradiol, 17α‐ethynylestradiol, and D‐estradiol 3‐methyl ether inhibited both monooxygenase reactions of cytochrome P‐450, whereas L‐estradiol 3‐methyl ether inhibited EO only. 17β‐Estradiol, 17α‐ethynylestradiol, and D‐estradiol 3‐methyl ether seem to act as free radical scavengers. From the results both structure activity relationships could be established and data on possible interferences with drug metabolism obtained. The enantiomers D‐ and L‐estradiol 3‐methyl ether differ in their effects on these systems.
Synthesis and Calcium Channel Modulating Effects of Isopropyl 1,4‐Dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(thienyl)‐5‐pyridinecarboxylates
Authors: Miri Ramin , Howlett Susan E. , Knaus Edward E. 
Published: October 2006

AbstractA group of racemic isopropyl 1,4‐dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(thienyl)‐5‐pyridinecarboxylates 7a–f were prepared using a modified Hantzsch reaction that involved the condensation of a thienylcarboxaldehyde 4a–f with isopropyl 3‐aminocrotonate 5 and nitroacetone 6. In vitro calcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle (GPILSM) assay. Compounds 7a–f exhibited weaker calcium channel antagonist activity (IC50 = 10−5 to 10−7 M range) than the reference drug nifedipine (IC50 = 1.43 × 10−8 M). The point of attachment of the C‐4 thienyl ring system was a determinant of antagonist activity [3‐thienyl (7b) > 2‐thienyl (7a)]. A 5‐substituent in the 2‐thienyl moiety influenced antagonist activity where the potency order was 5‐bromo‐2‐thienyl 7f ≥ 5‐methyl‐2‐thienyl 7c > 2‐thienyl 7a. Although the 5‐methyl‐2‐thienyl 7c and 3‐methyl‐2‐thienyl 7d isomers are equipotent antagonists, the 5‐bromo‐2‐thienyl compound 7f appears to be marginally more active than the 4‐bromo‐2‐thienyl isomer 7e. The 2‐thienyl compound 7a, unlike the 3‐thienyl isomer 7b, exhibited an agonist effect on GPILSM in the absence of the muscarinic agonist carbachol. Effects of the 2‐thienyl 7a and 3‐thienyl 7b isomers on the magnitude of calcium current were determined in guinea pig ventricular myocytes with voltage clamp techniques. Results showed that 2‐thienyl 7a inhibited calcium current (antagonist) when voltage steps were made from a potential of ‐40 mV. However, when voltage steps were made from ‐60 mV, 7a enhanced calcium current (agonist). The 3‐thienyl isomer 7b had little, if any, effect on calcium current.
An Improved Synthesis of the Anti‐Picornavirus Flavone 3‐O‐Methylquercetin
Authors: Boers Frank , Deng Bo‐Liang , Lemière Guy , Lepoivre Jozef , De Groot Alex , Dommisse Roger , Vlietinck Arnold J. 
Published: October 2006

AbstractTwo optimised procedures to synthesise 3‐O‐methylquercetin (1), an important antivirally active flavone, are presented: one is based on an Allan‐Robinson condensation, the other one on a modified phase transfer catalysed Baker‐ Venkataraman transformation.
Synthesis and Neuropeptide Y Y1 Receptor Antagonistic Activity of N,N‐Disubstituted ω‐Guanidino‐ and ω‐Aminoalkanoic Acid Amides
Authors: Müller Manfred , Knieps Sebastian , Geßele Karin , Dove Stefan , Bernhardt Günther , Buschauer Armin 
Published: October 2006

AbstractPotent arpromidine‐type histamine H2 receptor agonists such as BU‐E‐76 (He 90481) were among the first non‐peptides reported to display weak neuropeptide Y (NPY) Y1 receptor antagonist activity. In search of new chemical leads for the development of more potent NPY antagonists, a series of N,N‐disubstituted ω‐guanidino and ω‐aminoalkanoic acid amides were synthesized on the basis of structure‐activity relationships and molecular modeling studies of arpromidine and related imidazolylpropylguanidines. In one group of compounds the imidazole ring was retained whereas in the second group it was replaced with a phenol group representing a putative mimic of Tyr36 in NPY. Although the substitution patterns have not yet been optimized, the title compounds are NPY Y1 antagonists in human erythroleukemia (HEL) cells (Ca2+ assay) achieving pKB values in the range of 6.3–6.6. For representative new substances tested in the isolated guinea pig right atrium histamine H2 receptor agonism could not be found. In the N‐(diphenylalkyl)amide series, compounds with a trimethylene chain were more active Y1 antagonists than the ethylene homologs. Concerning the spacer in the ω‐amino or ω‐guanidinoalkanoyl portion, the best activity was found in compounds with a four‐ or five‐membered alkyl chain or a 1,4‐cyclohexylene group. Surprisingly, in contrast to the phenol series, in the imidazole series the compounds with a side chain amino group turned out to be considerably more potent than the corresponding strongly basic guanidines. Thus, the structure‐activity relationships appear to be different for the diphenylalkylamide NPY antagonists with one or two basic groups.
Determination of Fluoride Impurities in Calcium Ascorbate Comparison of Gas Chromatography and Ion Selective Electrode Potentiometry
Authors: Yuwono Mochammad , Ebel Siegfried 
Published: October 2006

AbstractFluoride impurities in pharmaceutical grade calcium ascorbate were determined analytically by capillary gas chromatography (GC) and ion‐selective electrode potentiometry (ISE). In the GC method, the amount of fluoride impurities was quantitatively analyzed following the conversion of fluoride to its corresponding trimethylsilane derivative using trimethylchlorsilane. The derivatization procedure was performed under acidic conditions and the generated trimethylfluorsilane was subsequently extracted with n‐hexane prior to GC analysis using isopentane as an internal standard.In the potentiometric method, the fluoride content was determined by relating the potential of the sample solution at different concentrations to a calibration curve. A comparative evaluation between the two methods was validated according to their linearity, precision, and accuracy. The fluoride concentrations found by means of GC and ISE were (0.94 ± 0.04) ppm and (0.85 ± 0.12) ppm, respectively. The student's t‐test (error of the first kind α = 0.1) indicated that there was no significant difference between the results obtained by the two methods.
Problems in using birth certificate files in the capture‐recapture model to estimate the completeness of case ascertainment in a population‐based birth defects registry in New York State
Authors: Wang Ying , Druschel Charlotte M. , Cross Philip K. , Hwang Syni‐An , Gensburg Lenore J. 
Published: October 2006

AbstractBACKGROUND: The limitations and underlying assumptions of the capture‐recapture methods have hindered their application in epidemiological settings, especially in evaluating the completeness of birth defects registries. This study explored the possibility of using birth certificates as the secondary data source in a simple two‐source capture‐recapture model to estimate the completeness of case ascertainment of the Congenital Malformations Registry (CMR) for selected major birth defects. METHODS: The CMR and the birth certificates were used as the primary and secondary sources, respectively. Children who were born in 1996–2001 and had selected major birth defects were identified from the two sources. The accuracy of the diagnoses was examined by comparing the individual birth defect categories of the children from the two sources. RESULTS: Discrepancies in birth defect categories in the two data sources and false positives in the birth certificates were the major problems encountered in estimating the completeness of the CMR using the simple two‐source capture‐recapture method. The estimated completeness for selected major birth defects was only about 71%. Stratified analyses resulted in relatively high estimated completeness for oral clefts (90%) and Down syndrome (88%). CONCLUSIONS Although the birth certificate data was not a good source for estimating the completeness of case ascertainment of the CMR using capture‐recapture methods, the analyses provided reasonable estimates for some conditions that were relatively easy to identify and diagnose at birth, such as oral clefts and Down syndrome. Birth Defects Research (Part A), 2006. © 2006 Wiley‐Liss, Inc.