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1. |
Editorial |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 572-572
R. W. Hartmann,
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ISSN:0365-6233
DOI:10.1002/ardp.19953280702
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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2. |
4,5‐Dihydro‐3‐(2‐pyrazinyl)naphtho[1,2‐c]pyrazole: A Potent and Selective Inhibitor of Steroid‐17α‐Hydroxylase‐C17,20‐Lyase (P450 17) |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 573-575
Rolf W. Hartmann,
Gerald A. Wächter,
Tom Sergejew,
Rieka Würtz,
Jörg Düerkop,
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ISSN:0365-6233
DOI:10.1002/ardp.19953280703
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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3. |
Construction of a Detailed Serotoninergic 5‐HT2aReceptor Model |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 577-584
Hans‐Dieter Höltje,
Uwe Klaus Jendretzki,
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摘要:
AbstractWe have been able to show that the most important 5‐HT2aantagonists and agonists, belonging to chemically diverse classes can be fitted accurately into a common pharmacophoric pattern. In this paper we make use of the developed pharmacophore models to construct a fragmental amino acid model reflecting binding properties and affinity data of the structures under study. The proposed fragment model is then superimposed onto the transmembraneous part of the 5‐HT2areceptor. For this purpose the helix coordinates from the known structure of bacteriorhodopsin serve as a matrix. New structures with high affinity for the 5‐HT2asites were designed and their biological activities were predicted on the basis of interaction energies calculated with the fragment model. The predicted data show excellent agreement with experimental binding affin
ISSN:0365-6233
DOI:10.1002/ardp.19953280704
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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4. |
Preparation andIn VitroPharmacology of 5‐HT4Receptor Ligands. Partial Agonism and Antagonism of Metoclopramide Analogous Benzoic Esters |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 585-594
Sigurd Elz,
Andreas Keller,
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摘要:
AbstractAlicyclic ester analogues of the gastroprokinetic benzamide metoclopramide (1) and its ester congener SDZ 205557 (2), a 5‐HT4receptor antagonist, were prepared byO‐alkylation of 4‐amino‐5‐chloro‐2‐methoxybenzoate withN‐(2‐chloroethyl) substituted alicyclic amines. The bromo and iodo analogue of compound13b(2‐(1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) were obtained by halogenation of dechloro‐13bwithN‐halogenated succinimides. The series was evaluated in functionalin vitroassays with regard to affinity for serotoninergic 5‐HT4, 5‐HT3and muscarinic M3receptors. The affinities for 5‐HT4and M3receptors were below 6.0 (pKBor pA2). On 5‐HT4receptors in guinea‐pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5‐HT4receptor agonism susceptible to blockade by SDZ 205557, a reference 5‐HT4receptor antagonist (pKb= 7.25 − 7.73 (guinea‐pig ileum) and 7.09 — 7.43 (rat oesophagus)). The relative agonist potency was in the range of 5 – 303 % (5‐HT: 100 %). Compound13band its bromo analogue17were the most potent esters of the series. The enantiomers of13g((R)‐ and (S)‐2‐(2‐methyl‐1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) interacted stereoselectively with 5‐HT4receptors and displayed enantiomeric potency ratios (R)/(S) of 4.3 — 8.7. There was an excellent correlation between (a) antagonist affinity on guinea‐pig ileum and rat oesophagus, (b) relative agonist potency on guinea‐pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (r2>0.91). The new compounds may serve as academic tools in evaluating the functional role of 5‐HT4receptors. The selective partial 5‐HT4receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or
ISSN:0365-6233
DOI:10.1002/ardp.19953280705
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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5. |
Third Generation Antitumor Platinum(II) Complexes of the [1‐(Fluoro/difluorophenyl)‐2‐phenylethylenediamine]platinum(II) Type |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 595-603
Ronald Gust,
Helmut Schönenberger,
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摘要:
AbstractThe diastereomeric 1‐(fluoro/difluorophenyl)‐2‐phenylethylenediamines (4‐fluoro:erythro‐1/threo‐1; 2,4‐difluoro:erythro‐2/‐threo‐2; 2,6‐difluoro:erythro‐3/threo‐3) and the diastereomeric 1‐(4‐fluorophenyl)‐2‐(3‐hydroxyphenyl)ethylenediamines (erythro‐4/‐threo‐4) were synthesized from appropriately substituted stilbenes by reaction with IN3and subsequent LiAlH4reduction. Coordination of the 1,2‐diphenylethylenediamines to platinum was carried out by use of K2PtI4. The water‐soluble aquasulfatoplatinum(II) complexes (erythro/threo‐1‐PtSO4‐erythro/threo‐4‐PtSO4) were obtained from the diiodoplatinum(II) complexes by reaction with Ag2SO4. Additionallyerythro/threo‐4‐PtSO4anderythro/threo‐4‐PtSO4were transformed into the dichloroplatinum(II) complexes (erythro/threo‐1‐PtCl2,erythro/threo‐4‐PtCl2) by treatment with KCl. In contrast to the less effectiveerythro‐configurated sulfatoplatinum(II) complexes thethreo‐analogues showed comparable or even superior activities to cisplatin on the human MDA‐MB‐231 breast cancer cell line. On the MXT‐M‐3.2 breast cancer of the mouse onlyerythro‐ andthreo‐4‐PtSO4caused similar effects like cisplatin. The strong inhibitory effect of the diastereomeric sulfatoplatinum(II) complexes on the P‐388 leukemia of the mouse was equal to that of cisplatin. On the latter
ISSN:0365-6233
DOI:10.1002/ardp.19953280706
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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6. |
Structure‐Activity Relationship Studies of CNS Agents, Part 23[1]):N‐(3‐Phenylpropyl)‐ andN‐[3(E)‐Cinnamyl]‐1,2,3,4‐tetrahydroisoquinoline Mimic 1‐Phenylpiperazine at 5‐HT1AReceptors |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 604-608
Jerzy L. Mokrosz,
Andrzej J. Bojarski,
Sijka Charakchieva‐Minol,
Beata Duszynska,
Maria J. Mokrosz,
Maria H. Paluchowska,
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摘要:
AbstractThe 5‐HT1Areceptor affinities and ionization constants of a set of 1‐arylpiperazine (4) 1,2,3,4‐tetrahydroisoquinoline (6), and ‐quinoline (7) containingN‐(ω‐arylalkyl) orN‐(E)‐cinnamyl substituents as well as two morpholine derivatives (8a, 8b) were determined. It was shown that some tetrahydroisoquinoline (6c, 6d) and morpholine (8a) derivatives were 5‐HT1Aligands equipotentto 1‐phenylpiperazine (4a) and 1,2,3,4,4a5‐hexahydropyrazino[1,2‐a]indole (5). On the basis of molecular modelling studies it was also demonstrated that6c, 6dand8amimicked very well the reference structures of4aand its rigid analog5. Another, more complex 1,2,3,4‐tetrahydroisoquinoline derivative3, which served as a model compound to confirm the previously reported 5‐HT1Abinding mode of derivatives1a–dand2, had the highest 5‐HT1Aaffinity (Ki= 6.7 ± 0.5 nM)
ISSN:0365-6233
DOI:10.1002/ardp.19953280707
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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7. |
Synthesis, Pharmacological Investigation and Computational Studies on a Tricyclic Ergoline Analog with Selective Dopamine Autoreceptor Activity |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 609-614
Peter Gmeiner,
Bernd Bollinger,
Joachim Mierau,
Georg Höfner,
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摘要:
AbstractThe novel aminobenzindolone8was prepared and evaluated as a potential antipsychotic agent. The target compound was synthesized in eight steps starting from the tetrahydrobenzindolone9. The key step of the synthesis was an electrophilic amination of the aromatic ketone11followed by reductive degradation when the diethoxymethyl group was employed for protection of the lactam nitrogen and also for the benzylic position 2a. Dopamine and serotonin receptor binding studies revealed8to be a potent and selective ligand at the D‐2 autoreceptor (ki= 4.0 nM). Furtherin vivostudies including the GBL‐test and locomotor activity measurements indicated agonistic activity of8at the prejunctional binding sites. Comparison ofab initiobased molecular electrostatic isopotential maps corroborates our hypothesis that the dopamine structure6, containing an intramolecular hydrogen bond donating effect of themeta‐HO‐group, represents the conformation which is active at the dopamine D‐2 aut
ISSN:0365-6233
DOI:10.1002/ardp.19953280708
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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8. |
Synthesis, Toxicological, Pharmacological, and Bronchodilating Activityin vitroof some Xanthineacetic Acid Derivatives |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 615-618
Plamen Peikov,
Nikolai Danchev,
Alexander Zlatkov,
Dimiter Ivanov,
Nadya Belcheva,
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摘要:
AbstractThe possibility of the preparation of some ester derivatives of dimethylxanthines from 1‐theobromine‐ and 7‐theophylline acetic acids and 7‐(2‐hydroxyethyl)‐theophylline by DCC/DMAP‐mediated esterification under mild conditions was studied. The structures of the compounds synthesized and by products isolated were demonstrated by microanalyses, UV‐, IR‐, and1H NMR data. Acute toxicity assessment of the compounds on mice showed that compounds4, 5, 6, and7are less toxic than aminophylline. A pharmacological study of thein vitrobroncholytic effect (IC50and pD2values) of the derivatives and aminophylline showed that the new compound4(1,2,3,6‐tetrahydro‐1,3‐dimethyl‐2,6‐dioxo‐7H‐purine‐7‐acetic acid 2‐(1,2,3,6‐tetrahydro‐1,3‐dimethyl‐2,6‐dioxo‐7H‐purine‐7‐yl)ethyl ester) has a strong bronchodilating effect on serotonine‐ and acetylcholine‐induced spasm in guinea pig trachea. The same compound does not influence barbiturate — induced hypnosis and locomotor activity, unlike to t
ISSN:0365-6233
DOI:10.1002/ardp.19953280709
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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9. |
Resolution, EPC‐Syntheses, Absolute Stereochemistry, and Pharmacology of the (S)‐(+)‐ and (R)‐(—)‐Isomers of the MAO‐A Inhibitor Tetrindole Hydrochloride |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 619-622
Michael Bös,
Rolf Canesso,
Rolf Kettler,
Hans H. Keller,
Peter Schönholzer,
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摘要:
AbstractResolution of (RS)‐tetrindole (3) and enantioselective reductions of the imine7yielded (S)‐(+)‐(4) and (R)‐(−)‐tetrindole (5). The absolute stereochemistry of4was established by X‐ray analysis of the corresponding Mosher amide6. Fromin vitroas well asin vivodata (MAO‐inhibiton, levels of monoamines and their respective metabolites in rat brain),4was identified
ISSN:0365-6233
DOI:10.1002/ardp.19953280710
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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10. |
Structure‐Activity Relationship Studies of CNS Agents, Part 22: A Search for New Trazodone‐Like Antidepressants: Synthesis and Preliminary Receptor Binding Studies |
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Archiv der Pharmazie,
Volume 328,
Issue 7‐8,
1995,
Page 623-625
Jerzy L. Mokrosz,
Beata Duszynska,
Maria H. Paluchowska,
S. Charakchieva‐Minol,
Maria J. Mokrosz,
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摘要:
AbstractNew 1‐phenyl‐ and 1‐(3‐chlorophenyl)piperazines containing a 4‐[3‐(heterocyclic)propyl] fragment were synthesized. It was found that of all the investigated compounds11b(Ki= 13 ± 2 nM) and8b(Ki= 38 ± 2 nM) were the most active 5‐HT1Aand 5‐HT2Aligands, respectively. Several derivatives (3a, 4a, 8b, 11b, 12b, 13a, and13b) were selected as good candidates for new, potential antidepressants on the basis of their 5‐HT1A/5‐HT2Arece
ISSN:0365-6233
DOI:10.1002/ardp.19953280711
出版商:WILEY‐VCH Verlag
年代:1995
数据来源: WILEY
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