bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untersuchungen zur Cyclokendensation von o‐aminophenyl‐substituierten Ketoximen und Amidoximen mit Carbonylverbindungen zu anellierten Chinazolinderivaten
Authors: Lessel Jürgen 
Published: October 2006

Abstracto‐Aminophenyl‐substituierte Ketoxime und Amidoxime 3 reagieren mit Aldehyden und Ketonen zu cyclischen Amidin‐ bzw. Chinazolin‐N‐oxiden 5, mit Diethylcarbonat ergibt Anthranilsäureamidoxim (3c) das Oxadiazolon 12. Dieses erfährt bei der Thermolyse eine Ringtransformation zu dem Aminoindazol 14, mit Ketonen erfolgt der Ringschluß zu den anellierten Chinazolinderivaten 22. Zur Erklärung des Reaktionsverlaufs werden semiempirische Molekülorbitalverfahren und die Störungstheorie herangezogen.
Heterocyclische Spirocyclohexadienone, 3. Mitt.
Authors: Möhrle Hans , Schake Dieter 
Published: October 2006

Abstract3‐Substituierte 2‐Naphtholderivate ergeben mit N‐Methyl‐2‐naphthylamin und Paraformaldehyd in guten Ausb. entspr. Spirocyclohexadienone, wobei auch 9‐Phenanthrol diesem Reaktionstyp zugänglich ist. Grundsätzlich liefern 4‐substituierte 1‐Naphthole ebenfalls Spiroketone, die jedoch labiler sind und in geringerem Ausmaß anfallen. Die Umsetzung der Spirocyclohexadienone mit Protonensäuren, Carbonylreagenzien und komplexen Hydriden wird untersucht und hieraus ein Reaktionsmechanismus abgeleitet.
Inhaltsstoffe tropischer Arzneipflanzen, 67. Mitt.: 24‐Acetylaminofevicordin D‐glucosid, ein artefizieller Inhaltsstoff von Fevillea cordifolia? — Zur Reaktivität der Fevicordine
Authors: Achenbach Hans , Horn Konrad , Waibel Reiner 
Published: October 2006

Abstract24‐Acetylaminofevicordin D‐glucosid (1) wurde als neue Nebenkomponente aus den Samen von Fevillea cordifolia (Cucurbitaceae) isoliert und seine Struktur mit spektroskopischen Methoden aufgeklärt. Wie Experimente zeigten, reagiert das Enon‐System in der Seitenkette von Fevicordin A‐glucosid (2), dem Hauptinhaltsstoff der Samen, mit Nucleophilen in einer Michael‐Addition. Mit Ammoniak verläuft diese Reaktion besonders leicht, wobei gleichzeitig die Acetylgruppe vom Sauerstoff an C‐25 zum Stickstoff wandert. 1 muß daher möglicherweise als Artefakt angesehen werden.
Third Generation Antitumor Platinum(II) Complexes of the [1‐(Fluoro/difluorophenyl)‐2‐phenylethylenediamine]platinum(II) Type
Authors: Gust Ronald , Schönenberger Helmut 
Published: October 2006

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 IN3 and subsequent LiAlH4 reduction. 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. Additionally erythro/threo‐4‐PtSO4 and erythro/threo‐4‐PtSO4 were transformed into the dichloroplatinum(II) complexes (erythro/threo‐1‐PtCl2, erythro/threo‐4‐PtCl2) by treatment with KCl. In contrast to the less effective erythro‐configurated sulfatoplatinum(II) complexes the threo‐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 only erythro‐ and threo‐4‐PtSO4 caused 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 tumor threo‐4‐PtCl2 was the most active among the less toxic dichloroplatinum(II) derivatives.
Synthesis, Pharmacological Investigation and Computational Studies on a Tricyclic Ergoline Analog with Selective Dopamine Autoreceptor Activity
Authors: Gmeiner Peter , Bollinger Bernd , Mierau Joachim , Höfner Georg 
Published: October 2006

AbstractThe novel aminobenzindolone 8 was prepared and evaluated as a potential antipsychotic agent. The target compound was synthesized in eight steps starting from the tetrahydrobenzindolone 9. The key step of the synthesis was an electrophilic amination of the aromatic ketone 11 followed 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 revealed 8 to be a potent and selective ligand at the D‐2 autoreceptor (ki = 4.0 nM). Further in vivo studies including the GBL‐test and locomotor activity measurements indicated agonistic activity of 8 at the prejunctional binding sites. Comparison of ab initio based molecular electrostatic isopotential maps corroborates our hypothesis that the dopamine structure 6, containing an intramolecular hydrogen bond donating effect of the meta‐HO‐group, represents the conformation which is active at the dopamine D‐2 autoreceptor.
Chemotactic Peptide Analogues. Synthesis and Chemotactic Activity of N‐Formyl‐Met‐Leu‐Phe Analogues Containing (S)‐Phenylalaninol Derivatives
Authors: Zecchini Giampiero Pagani , Paradisi Mario Paglialunga , Torrini Ines , Spisani Susanna 
Published: October 2006

AbstractThe synthesis and the biological activity towards human neutrophils of some N‐formyl‐Met‐Leu‐Phe‐OMe analogues containing (S)‐phenylalaninol (Pheol) or its derivatives in place of the native phenylalanine are reported. While the analogue containing Pheol (4) was found to be devoid of significant biological activity, its esters 3 and 5, although inactive as chemoattractants, are able to strongly stimulate superoxide production and are active with a lower efficacy in the lysozyme release.
Synthesis of New 2‐{[(Phenoxy or Phenyl)acetyl]amino}benzoic Acid Derivatives as 3α‐Hydroxysteroid Dehydrogenase Inhibitors and Potential Antiinflammatory Agents
Authors: Daidone Giuseppe , Plescia Salvatore , Bajardi Maria Luisa , Schillaci Domenico 
Published: October 2006

AbstractA number of 2‐{[(phenoxy or phenyl)acetyl]amino}benzoic acid derivatives were prepared in about 50% yield from (phenoxy or phenyl)acetyl chloride and anthranilic acid derivatives. All the compounds were tested as in vitro inhibitors of 3α‐hydroxysteroid dehydrogenase, since enzyme inhibition predicts potential antiinflammatory activity in vivo The most active compounds 3 1, m, s are about 3.5 times more active than acetylsalicylic acid (ASA). Activity is influenced by electronic as well as steric effects.
Anti‐Elastase and Anti‐Hyaluronidase Activities of Saponins and Sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: Factors Contributing to their Efficacy in the Treatment of Venous Insufficiency
Authors: Facino Roberto Maffei , Carini Marina , Stefani Rita , Aldini Giancarlo , Saibene Luisella 
Published: October 2006

AbstractTriterpene and steroid saponins and sapogenins of medicinal plants (Aesculus hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be effective for the treatment/prevention of venous insufficiency. In this work we evaluated the inhibitory effects of these plant constituents on the activity of elastase and hyaluronidase, the enzyme systems involved in the turnover of the main components of the perivascular amorphous substance.The results evidence that for Hedera helix L., the sapogenins only non‐competitively inhibit hyaluronidase activity in a dose‐dependent fashion, showing comparable IC50 values (hederagenin IC50 = 280.4 μM; oleanolic acid IC50 = 300.2 μM); both the saponins hederacoside C and α‐hederin are very weak inhibitors.The same behaviour is observed for serine protease porcine pancreatic elastase: the glycosides are devoid of inhibitory action, while genins are potent competitive inhibitors (oleanolic acid IC50 = 5.1 μM; hederagenin IC50 = 40.6 μM). Constituents from Aesculus hippocastanum L. show inhibitory effects only on hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 = 149.9 μM), less to its genin escinol (IC50 = 1.65 μM).By contrast, ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity, exhibit remarkable anti‐elastase activity (IC50 = 119.9 μM; competitive inhibition). The mechanism of elastase inhibition by triterpene and steroid aglycones, with a nitroanilide derivative as substrate, is discussed.
Peroxides as Constituents of Plants, Part 19: A C50‐Hydroperoxide from Hypericum perforatum
Authors: Rücker Gerhard , Manns Detlef , Hartmann Rudolf , Bonsels Ulrike 
Published: October 2006

AbstractA new C50‐hydroperoxide (1) with a hitherto unknown constitution, containing cadinane hydroperoxide and hyperforin (2) as partial structures, was isolated from the stems and leaves of St. John's wort (Hypericum perforatum L., Hypericaceae). The structure was elucidated by high‐resolution NMR techniques (1D and 2D NMR experiments).
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, Part 31: Distribution Behaviour of 131‐Iodine Labelled trans‐N,N′‐Bis‐(ethoxy‐carbonyl)‐N‐[4‐(3‐iodo‐4‐methoxyphenyl)butyl]‐N′‐5‐phenylpentyl)‐1,4‐cyclohexanedimethanamine
Authors: Rehse Klaus , Wolf Stefan , Buck Wolfgang , Wenzel Martin 
Published: October 2006

AbstractThe title compound 9, which is a prodrug, and its active metabolite 7 were labelled with 131I (7*/9*) to investigate their pharmacokinetic behaviour, including the distribution between stomach, gut, muscle, blood, lung, liver, kidney, adrenal gland, heart, and spleen. Four hours after oral administration of 7* to mice only 3% of the dose had been absorbed from the g.i. tract. After 24 h 54 % of the radioactivity still is found the gut, predominantly in the small intestine. These results explain why 7, which is a potent antiplatelet drug in vitro, shows no antithrombotic effect in vivo. In contrast, the produg 9/9* is absorbed considerably, i.e. up to 50 % in 4 h from the g.i. tract depending on the dose applied and the vehicle used. At doses in the micromolar range the absorption appears to be diffusion limited. The highest concentrations are found in the liver and the kidneys suggesting a first pass effect of 7 followed by renal excretion. From the blood levels achieved, the dose nessessary for an antithrombotic effect has been calculated to be about 100 mg/kg. In summary, the N‐ethoxycarbonyl derivatives of oligoamines appear to be suitable prodrugs for oral administration of oligoamines.
Synthesis and Calcium Channel Modulating Effects of Alkyl 1,4‐Dihydro‐2,6‐dimethyl‐4‐(pyridinyl or 2‐trifluoromethylphenyl)‐5‐(1H‐tetrazol‐5‐yl)‐3‐pyridinecarboxylates
Authors: Iqbal Nadeem , Knaus Edward E. 
Published: October 2006

AbstractA group of racemic alkyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(pyridinyl or 2‐trifluoromethylphenyl)‐5‐(1H‐tetrazol‐5‐yl)‐3‐pyridinecarboxylates 11–14 were prepared using the Hantzsch reaction that involved the condensation of 2‐, 3‐ or 4‐pyridinecarboxaldehyde, or 2‐trifluoromethylbenzaldehyde, 8a–d with isopropyl or methyl 3‐aminocrotonate (9a–b) and 5‐(2‐oxopropyl)‐1H‐tetrazole (10a) or 5‐(2‐oxopropyl)‐1‐methyl‐1H‐tetrazole (10b). In vitro calcium channel (CC) antagonist and agonist activities were determined using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays, respectively. In the series of compounds 11–14, only compounds 14a and 14b exhibited some weak CC antagonist activity (10−6 M range) relative to the reference drug nifedipine (IC50 = 1.43 × 10−8 M). Compounds 11b‐14b having a 1‐methyl‐1H‐tetrazol‐5‐yl substituent were inactive CC agonists on GPLA. In contrast, compounds 12a‐14a having a 1H‐tetrazol‐5‐yl substituent exhibited CC agonist activity on GPLA, but the C‐4 2‐pyridinyl analog 11a exhibited a mild negative inotropic effect. The approximately equipotent CC agonist activity (GPLA) exhibited by the C‐4 pyridinyl 13a and 4‐(2‐trifluoromethylphenyl) 14a compounds compared favorably with that of the reference drug (±)‐Bay K 8644 (EC50 = 7.7 × 10−7 M) indicating that the 1H‐tetrazol‐5‐yl moiety is a suitable replacement for the nitro group present in Bay K 8644 with respect to cardiac CC agonist activity. These latter compounds 13a and 14a should serve as useful probes to study the structure‐function relationships of calcium channels.
Sensitizing Properties of New N‐(2‐Arylalkyl) Propionamides in Drug‐Sensitive and Multidrug‐Resistant Tumor Cells
Authors: Ros Francisco , García Rocío , Rivera‐Fillat Maria Pilar , González Miguel A. , Grau‐Oliete Maria Rosa 
Published: October 2006

AbstractThe propionamides 5 and 6 have been synthesized and tested for stimulation of antitumor drug activity. 5 and 6b increase vincristine cytotoxicity in drug‐sensitive murine tumor cells; 5 also increases the toxicity in multidrug resistant cells. Dissimilar trends in sensitive and resistant cells have been observed for the stimulating activity of several propionamides of this family and structurally related verapamil with their molar refractivity, suggesting different size requirements for the sensitizers in sensitive and resistant cells.
New NO‐Donors with Antithrombotic and Vasodilating Activities, Part 13: Pyrazol‐4‐one 1,2‐Dioxides and 4‐Hydroxyiminopyrazole 1,2‐Dioxides
Authors: Rehse Klaus , Müller Ulrich 
Published: October 2006

AbstractTwenty pyrazol‐4‐one 1,2‐dioxides and eleven 4‐hydroxyiminopyrazole 1,2‐dioxides were prepared and tested for their antiplatelet activity (Born test with collagen). Six compounds which all belong to the pyrazolone series inhibited the platelet aggregation half‐maximally in submicromolar concentrations (200–800 nmol/L). In positions 3 and 5, these compounds bear at least one (15, 16, 24, 31) or two substituents (7, 29) with electron‐withdrawing groups. Among them are aromatic moieties like 4‐hydroxysulfonylphenyl (7), 4‐cyanophenyl (16), 4‐chlorophenyl (15), phenyl (24) or carboxylic acid esters (29). Two compounds were investigated in an in vivo thrombosis model (1, 31). 2h after oral administration of 60 mg/kg 1 to rats in arterioles 69 % inhibition of thrombus formation (venules 40 %) was observed.
(2E,4E)‐N‐(4‐(1H‐Indol‐3‐yl)piperidin‐1‐yl)alkyl‐5‐(substituted phenyl)‐2,4‐pentadienamides as Antiallergic Agents with Antihistaminic and Anti Slow‐Reacting Substance (SRS) Activities
Authors: Shigenaga Shinji , Manabe Takashi , Matsuda Hiroshi , Fujii Takashi , Matsuo Masaaki 
Published: October 2006

AbstractAs an extension of our study aiming to discover a novel compound with dual activities against histamine and slow‐reacting substance (SRS), we synthesized two types of indolylpiperidine derivatives, 3 and 4–20. Testing for in vivo antianaphylactic activity and for in vitro anti‐SRS activity revealed that (2E,4E)‐5‐(3,5‐dimethoxy‐4‐hydroxyphenyl)‐N‐(2‐(4‐(1H‐indol‐3‐yl)piperidin‐1‐yl)ethyl)‐2,4‐pentadienamide (11) exhibited potent dual activities with ED50 = 0.89 mg/kg and IC50 = 1.43 μM, respectively. However, the plasma concentration of unchanged 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjugate.
Reduced Flexibility Analogs of Analgesic and Cognition Enhancing α‐Tropanyl Esters
Authors: Manetti Dina , Romanelli Maria Novella , Bartolini Alessandro , Dei Silvia , Ghelardini Carla , Gualtieri Fulvio , Matucci Rosanna , Scapecchi Serena , Teodori Elisabetta 
Published: October 2006

AbstractA series of semirigid analogs of compounds 1 and 2, two potent analgesics and cognition enhancers, have been synthesized and tested for antinociceptive activity (hot plate test) and for muscarinic affinity (binding in rat cerebral cortex). They were found to be in general less potent than the reference compounds; only one of them (22) shows a good affinity for the muscarinic receptor and an antinociceptive efficacy comparable with those of the reference compounds. At a dose of 30 mg/kg 22 is also able to reverse the amnesic effect of dicyclomine. Since the analgesic effect of these compounds is affected by the 5‐HT4 antagonist SDZ 205557, the possible role of this receptor is discussed.
Benzimidazole‐type Glycine Antagonists: The Role of the Ring Nitrogen Atoms
Authors: Berger Michael L. , Schödl Clemens , Noe Christian R. 
Published: October 2006

AbstractSeveral derivatives of 1H‐benzimidazole‐2‐carboxylic acid (BICA, 2a) were tested in vitro in comparison to 1H‐indole‐2‐carboxylic acid (ICA, 1e) for their ability to displace [3H]glycine from rat hippocampal membranes. Compound 2a was 8 times more potent than 1e (Ki 5.3 μM, as compared to 42 μM). However, introduction of a carboxymethyl group or a corresponding ester at position 3 had no positive effect on the potency of 2a, while this type of structural modification increased the potency of 1e significantly. Nevertheless, 1‐carboxymethyl‐BICA (2b) displaced [3H]glycine with similar potency as the corresponding 3‐carboxymethyl‐ICA 1c, indicating that also a nitrogen atom lacking a hydrogen atom can be engaged in glycine receptor interaction. N‐Methylation strongly reduced the potencies of both BICA and ICA derivatives.
Chemotactic Peptide Analogues The Role of (Z)‐2,3‐Didehydrophenylalanine and Phenylalanine C‐Terminal Residues in Determining the Chemotactic Activity of Formylpeptides
Authors: Torrini Ines , Zecchini Giampiero Pagani , Paradisi Mario Paglialunga , Spisani Susanna 
Published: October 2006

AbstractSeveral formylpeptides, analogs of the chemotactic agent HCO‐Met‐Leu‐Phe‐OMe, having the HCO‐Xaa‐Leu‐ΔzPhe‐OMe and HCO‐Xaa‐Leu‐ΔzPhe‐Phe‐OMe structures (ΔzPhe = (Z)‐2,3‐didehydrophenylalanine), have been synthesized. The biological activity of these ligands has been determined on human neutrophils and compared to that of the corresponding HCO‐Xaa‐Leu‐Phe‐OMe derivatives not containing the unsaturated residue. The replacement of the C‐terminal Phe with ΔzPhe causes, in all the examined tripeptides, the loss of any biological activity. On the other hand, the introduction into the ΔzPhe containing models of an additional C‐terminal Phe residue leads to the formyltetrapeptides HCO‐Xaa‐Leu‐ΔzPhe‐Phe‐OMe which show a biological activity very similar to that exhibited by the corresponding HCO‐Xaa‐Leu‐Phe‐OMe analogues.
New Potent Azomethine Prodrugs of the Histamine H3‐Receptor Agonist (R)‐α‐Methylhistamine Containing a Heteroarylphenyl Partial Structure
Authors: Krause Michael , Rouleau Agnès , Stark Holger , Luger Peter , Garbarg Monique , Schwartz Jean‐Charles , Schunack Walter 
Published: October 2006

AbstractThe therapeutic value of histamine H3‐receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H3‐receptor agonist (R)‐α‐methyl‐histamine (1) a series of new azomethine prodrugs containing five‐ and six‐membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron‐deficient six‐membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five‐membered heterocycles appeared to be highly effective for the CNS delivery of 1, and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)‐4‐fluoro‐2‐[[N‐[1‐(1H‐imidazol‐4‐yl)‐2‐propyl]imino](1H‐pyrrol‐2‐yl)methyl]phenol (8c), the 2‐furanyl analogue 8d, and its 3‐furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H3‐receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.
Synthesis and Antimicrobial Activity of New Quaternary Ammonium Chlorides
Authors: Brycki Bogumil , Skrzypczak Andrzej , Mirska Ilona , Pernak Juliusz 
Published: October 2006

AbstractDecyldimethylamine reacts readily with chloromethylalkyl ethers or sulfides, chloromethylbezyl ethers or sulfides and chloromethylcycloalkyl ethers to give quaternary ammonium chlorides in very good yields. All the chlorides studied showed antimicrobial activity. The relationship between the chemical structure and antimicrobial activity was analyzed by rough sets.
Search for the Pharmacophore in Kappa‐agonistic Diazabicyclo[3.3.1]nonan‐9‐one‐1,5‐diesters and Arylacetamides
Authors: Brandt Wolfgang , Drosihn Susanne , Haurand Michael , Holzgrabe Ulrike , Nachtsheim Corina 
Published: October 2006

AbstractSeveral heterocyclic bicyclo[3.3.1]nonan‐9‐ones were found to have a high affinity to k opioid receptors. 3,7‐Diazabicyclononanones with 2,4‐dipyridyl side chains were the most potent agonists whereas the corresponding 3‐oxa‐7‐azabicyclo[3.3.1]nonan‐9‐one and compounds with phenyl substituents in 2 and 4 position are almost inactive. The purpose of this study was to unravel the active conformation of the bicyclononanones using well‐known k‐selective agonists such as ketocyclacocine, arylacetamides, several isoquinolines, CI‐977, and four stereoisomers of EMD‐61753 for comparison. In order to determine the geometry of the diazabicycles in solution pH‐dependent NMR measurements of the bicycles were recorded and the results were related to the geometries of the aforementioned k agonists obtained from semiempirical PM3 calculations. A chair‐boat conformation and a protonation at the N7 nitrogen atom of the diazabicyclononanones were found to be the pharmacophoric conformation. Comparison of the spatial arrangements, electrostatic, hydrophobic, and hydrogen bonding potentials of all k‐selective agonists led to a model of structure‐activity relationships of ligands of the k‐receptor. The arrangement of the pharmacophoric elements is characterized by an almost parallel orientation of a carbonyl and a protonated NH function in conjunction with at least one aromatic ring. Ketocyclazocine is only able to adopt this parallel orientation when the nitrogen is inverted relative to the X‐ray structure. Furthermore, two binding sites for the aromatic rings are discussed. The pharmacological results of all considered bicyclononanone derivatives as well as of the four enantiomers of EMD‐61753 can be understood and consistently explained in this way.
3‐(Octadecanoylaminomethyl)indole‐2‐carboxylic Acid Derivatives and 1‐Methyl‐3‐octadecanoylindole‐2‐carboxylic Acid as Inhibitors of Cytosolic Phospholipase A2
Authors: Lehr Matthias 
Published: October 2006

Abstract3‐(1‐Acylaminooctadecyl)indole‐2‐carboxylic acids and 3‐(1‐acylaminooctadecyl)‐1‐methylindole‐2‐carboxylic acids were designed and synthesized as inhibitors of cytosolic phospholipase A2. Enzyme inhibition was assayed by evaluation of calcium ionophore A23187‐induced arachidonic acid release from bovine platelets. While compounds with 1‐octadecanoylaminooctadecyl groups in position 3 of the indole were inactive inhibition data for 3‐[1‐(3‐phenylpropionylamino)octadecyl]indole‐2‐carboxylic acids could not be evaluated because of lysis of the platelets. However 3‐(octadecanoylaminomethyl)indole‐2‐carboxylic acid derivatives and 1‐methyl‐3‐octadecanoylindole‐2‐carboxylic acid proved to be inhibitors of cytosolic phospholipase A2. The most active inhibitor was the latter compound with an IC50 of 8 μM.