bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Pyrryl Aryl Sulfones Targeted at the HIV‐1 Reverse Transcriptase
Authors: Artico Marino , Silvestri Romano , Stefancich Giorgio , Massa Silvio , Pagnozzi Eugenia , Musu Daniela , Scintu Franca , Pinna Elisabetta , Tinti Enrico , La Colla Paolo 
Published: October 2006

AbstractVarious aryl 1‐pyrryl sulfones were synthesized and tested as inhibitors of HIV‐1, 2‐Nitrophenyl‐2‐ethoxycarbonyl‐1‐pyrryl sulfone, the most active among test derivatives, was selected as lead compound of the aryl pyrryl sulfone series. The in vitro anti‐HIV‐1 activity and cytotoxicity of 41 compounds is reported. Some structure‐activity relationships are discussed also in comparison with the known NPPS (2‐nitrophenyl phenyl sulfone).
Synthesis and Biochemical Evaluation of (Carbamoylalkenyl)phenyloxy Carboxylic Acid Derivatives as Non‐steroidal 5α‐Reductase Inhibitors
Authors: Kattner Lars , Göhring Sigrid , Hartmann Rolf W. 
Published: October 2006

AbstractSeveral (carbamoylalkenyl)‐ and (carbamoylalkenyl)phenyloxy carboxylic acids (Table 1) and some of their ethyl esters (Table 2) were synthesized and evaluated in vitro as inhibitors of steroid 5α‐reductase. Inhibitors of this enzyme may be useful in treating dihydrotestosterone‐related diseases such as prostate cancer and benign prostatic hyperplasia. Using an enzyme preparation obtained from human prostate carcinoma tissue, the inhibition values ranged from 0 to 57 % at the given dose of 100 μM. In the series of free acids, surprisingly, the compounds showed only modest inhibitory potency (0–26 %). By contrast, the ethyl esters displayed inhibition values up to 57 %. Structure‐activity relationships are discussed.
Synthesis of (S)‐3,4‐Diaminobutanenitriles as Precursors for 3‐Amino‐GABA Derivatives
Authors: Gmeiner Peter , Hummel Evi , Haubmann Christian , Höfner Georg 
Published: October 2006

AbstractStarting from natural asparagine (1) a synthesis of the protected (S)‐3,4‐diaminobutanenitriles 5 and 8a–c via the β‐homoserine derivative 2 is described. The amino function in position 4 was introduced by Mitsunobu‐coupling or by reductive amination when a strange deformylation of the amino aldehyde 7 was observed as a side reaction. The Mitsunobu‐product 5 was converted into the dibenzylamine substituted GABA 6b which was investigated for its affinity at the GABA‐A receptor.
Synthese und Pharmakodynamische Aktivität von 2‐(3‐(2‐Phenylethyl)benzofuran‐2‐yl)‐N‐propyl‐ethanamin
Authors: Ecker G. , Helml T. , Fleischhacker W. , Noe C. R. , Studenik Christian , Schade Bettina , Heistracher Peter 
Published: October 2006

AbstractIm Rahmen von Struktur‐Wirkungs‐Untersuchungen an Klasse I‐Antiarrhythmika wurden die Benzofuranethanamine 3a und 3b synthetisiert, und 3a wurde pharmakologisch geprüft. Schlüsselschritt der Synthese war die chemoselektive Reduktion des Chloracetyl‐Dihydrobenzofurans 5 zum Chlorethylbenzofuran 9 mit Triethylsilan/BF3 · Et2O. Die Ergebnisse einer Reihe weiterer Reduktionsversuche von 5 werden ebenfalls beschrieben. Pharmakologische Untersuchungen an isolierten Präparaten von Meerschweinchenherzen zeigten, daß 3a eine ähnliche negativ inotrope und chronotrope Wirkung wie Propafenon und das entsprechend rigidisierte Benzofuran 1a besitzt. Im Unterschied zu diesen Substanzen zeigte 3a jedoch keine β1‐Adrenozeptoren‐blockierende Aktivität.
Acidity and Stability of 10‐Substituted 1,8‐Dihydroxy‐9(10H)‐anthracenones
Authors: Müller Klaus , Gawlik Ingo , Wiegrebe Wolfgang 
Published: October 2006

AbstractThe decomposition of 10‐substituted anthralin derivatives in dimethyl sulfoxide and ethanol was determined. While 10‐ω‐phenylalkylidene derivatives were thoroughly stable, 10‐ω‐phenylacyl‐substituted compounds were slowly degraded to danthron and the corresponding carboxylic acids. However, the stability of these derivatives was markedly improved as compared to that of anthralin. Determination of the pKa values showed that the ω‐phenylacyl derivatives were somewhat stronger acids than anthralin, while ω‐phenylalkylidene‐substitution generally leaves the acidity of the anthralin part unchanged.
Structure‐Activity Relationship Studies of CNS Agents, XXI: Two Derivatives of 1‐(o‐Methoxyphenyl)piperazine with an Opposite Function at 5‐HT1A Receptors
Authors: Mokrosz Jerzy L. , Klodzinska Aleksandra , Boksa Jan , Bojarski Andrzej J. , Duszynska Beata , Chojnacka‐Wójcik Ewa 
Published: October 2006

AbstractIt is intriguing that all postsynaptic 5‐HT1A receptor antagonists which belong to the 1‐arylpiperazine class of ligands have a 1‐(o‐methoxyphenyl)‐piperazine fragment or its structural equivalent (e.g. benzodioxane moiety) in their structure2–5). One of them, NAN‐190 (1) may be regarded as a classic postsynaptic 5‐HT1A antagonist whose pharmacological and biochemical profiles have been well recognized2,6,7). Moreover, regarding all the known 5‐HT1A antagonists, systematic structure‐activity studies have been conducted for NAN‐190 only, as yet2,5,8,9).Recently we showed that the simplification of the amide portion in NAN‐190 (1) did not change its in vivo profile; moreover, MM‐77 (2) also appeared to be a potent postsynaptic antagonist of 5‐HT1A receptors5). Even more dramatic structure simplification (of. 3 vs. 1) did not abolish the antagonistic properties of 3. According to Glennon and coworkers, compound 3 behaved like a weak postsynaptic 5‐HT1A antagonist in some biochemical tests8.9). By contrast, replacement of the 1‐(o‐methoxyphenyl)piperazine fragment in NAN‐190 by a bridged 1‐phenylpiperazine ring system resulted in analog 5, which was completely inactive in the in vivo models used5).
Biomimetic Aromatic Hydroxylation of Selected Diphenylmethane Derivatives
Authors: Fröhlich Luela , Pietzyk Birgit , Göber B. 
Published: October 2006

AbstractMany oxidation systems using iron or manganese porphyrins as catalysts and various oxygen atom donors have been reported to mimic cytochrome P‐450‐dependent monooxygenases1–3). Such systems are very efficient for epoxidation of alkenes and reasonably for alkane hydroxylation. Few authors also reported about the activity to hydroxylate aromatic rings. In these cases low yields were found for hydroxylation of anisole, benzene, naphthalene, and toluene4–7). Biomimetic systems based on metalloporphyrin catalysts can be used for preparative oxidation of some substrates and appear particularly useful for the preparation of oxidized metabolites of drugs or other xenobiotics.
The N‐(9‐Xanthenyl) Derivative of 2‐Carbamoylphenoxyacetic Acid
Authors: Benicke Stephan , Grigat Hartmut 
Published: October 2006

AbstractDerivatisierungen sind neben Farbreaktionen geeignete Methoden zur Identifizierung und Charakterisierung organischer Verbindungen. Daher werden in zunehmendem Maße auch in der pharmazeutischen Analytik bestimmte Arzneistoffe, z.B. solche mit aciden NH‐Funktionen, durch Derivatisierung mit Xanthydrol (9‐Xanthenol, 1) identifiziert und charakterisiert1,2). Xanthydrol ist auch ein Reagenz des Arzneibuches, wobei das dort angewandte Verfahren der Xanthenylierung von Harnstoff umgekehrt zur quantitativen Bestimmung des Xanthydrols dient3,4).Auf Grund ihres NH‐aciden Charakters liefern insbesondere unsubstituierte Säureamide in glatter Kondensation zumeist gut kristallisierende Xanthydrol‐Derivate5).
Regioisomeric 5(3)‐Aminomethyl‐3(5)‐phenylisoxazoles: Synthesis, Spectroscopic Discrimination, and Muscarinic Activity
Authors: Dannhardt Gerd , Lambrecht Günter , Laufer Stefan , Mutschler Ernst , Schweiger Johannes 
Published: October 2006

AbstractThe regioselective synthesis of isomeric 5(3)‐aminomethyl‐3(5)‐phenyl isoxazoles using different methods is described. Spectroscopic data, especially mass spectrometric fragmentation, were used to identify and characterize the regioisomers. The muscarinic activity of these isoxazoles was assayed on isolated guinea‐pig ileum and atria as well as on isolated rabbit vas deferens.
Polarographische Untersuchung von Nedocromil, 2. Mitt: Polarographie von Nedocromil‐Natrium
Authors: Hermening Petra , Hoffmann Hermann 
Published: October 2006

AbstractNedocromil‐Natrium 1 zeigt ein stark pH‐abhängiges Reduktionsverhalten. Während im Bereich pH 2–5 zwei Stufen zu beobachten sind, wobei Stufe 1 in zwei Teilprozesse (1a und 1b) aufgespalten ist, tritt bei pH 6 erstmalig eine 3. Stufe auf. Bei pH‐Werten > 7 sind im Gleichspannungspolarogramm nur noch die Stufen 1a, 2 und 3 vorhanden. Zur kompletten Reduktion von 1 werden insgesamt acht Elektronen pro Molekül transferiert, es werden beide α,β‐ungesättigten Ketofunktionen zu den entsprechenden gesättigten Carbinolen reduziert.Die Aufklärung des Reduktionsmechanismus wurde durch vergleichende Untersuchungen an Chromon‐2‐carbonsäure 2 und N‐Ethylchinoloncarbonsäure 31) unterstützt.
Synthesis and Antibiotic Activity of 1‐Cycloalkoxymethyl‐4‐dimethylaminopyridinium and 1‐[(1‐Alkoxy)ethyl]‐4‐dimethylaminopyridinium Chlorides
Authors: Pernak Juliusz , Michalak Lucyna , Krysinski Jerzy , Kuncewicz Zbigniew 
Published: October 2006

AbstractDMAP reacts readily with chloromethylcycloalkyl ethers and α‐chloroethyl alkyl ethers to give stable (1a–1e) and unstable (2a–2h) pyridinium chlorides. Reaction of these chlorides with NaOH produces the corresponding 4‐pyridones. All the chlorides synthesized showed antibiotic activity. Particularly high activity against microbes representing cocci, rods, fungi, and bacilli was shown by 1‐cyclododecyloxymethyl‐4‐dimethylaminopyridinium chloride 1d and 1‐[(1‐dodecyloxy)ethyl]‐4‐dimethylaminopyridinium chloride 2f.
Structure‐Activity Relationship Studies of CNS Agents, Part 23[1]): N‐(3‐Phenylpropyl)‐ and N‐[3(E)‐Cinnamyl]‐1,2,3,4‐tetrahydroisoquinoline Mimic 1‐Phenylpiperazine at 5‐HT1A Receptors
Authors: Mokrosz Jerzy L. , Bojarski Andrzej J. , Charakchieva‐Minol Sijka , Duszynska Beata , Mokrosz Maria J. , Paluchowska Maria H. 
Published: October 2006

AbstractThe 5‐HT1A receptor affinities and ionization constants of a set of 1‐arylpiperazine (4) 1,2,3,4‐tetrahydroisoquinoline (6), and ‐quinoline (7) containing N‐(ω‐arylalkyl) or N‐(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‐HT1A ligands 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 that 6c, 6d and 8a mimicked very well the reference structures of 4a and its rigid analog 5. Another, more complex 1,2,3,4‐tetrahydroisoquinoline derivative 3, which served as a model compound to confirm the previously reported 5‐HT1A binding mode of derivatives 1a–d and 2, had the highest 5‐HT1A affinity (Ki = 6.7 ± 0.5 nM) of all the investigated compounds.
Synthesis, Toxicological, Pharmacological, and Bronchodilating Activity in vitro of some Xanthineacetic Acid Derivatives
Authors: Peikov Plamen , Danchev Nikolai , Zlatkov Alexander , Ivanov Dimiter , Belcheva Nadya 
Published: October 2006

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‐, and 1H NMR data. Acute toxicity assessment of the compounds on mice showed that compounds 4, 5, 6, and 7 are less toxic than aminophylline. A pharmacological study of the in vitro broncholytic effect (IC50 and pD2 values) of the derivatives and aminophylline showed that the new compound 4 (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 the effect of the aminophylline, used as a reference substance.
Proof of the Bis(oxazolidine)methane Structure for the Norephedrine—Formaldehyde Condensation Product
Authors: Aitken David J. , Chiaroni Angèle , Riche Claude , Husson Henri‐Philippe 
Published: October 2006

AbstractThe norephedrine—formaldehyde condensation product, a potential prodrug, was shown to have a bis(oxazolidine)methane structure by an X‐ray crystallography study.
Synthesis, Antitumoral and Antiviral Evaluation of Halo‐ and Demethyl‐Yatein Derivatives
Authors: Medarde Manuel , de Clairac Rafael Peláez‐Lamamié , López Jose Luis , Grávalos Dolores Ga , Feliciano Arturo San 
Published: October 2006

AbstractSeveral chloro‐ and iodo‐lignanolides have been obtained by direct halogenation of aromatic rings from yatein and 4′‐O‐demethylyatein. They were assayed as antineoplastics, in order to check the influence in the activity of substitution in both aromatic rings. Although these compounds show a modest antineoplastic activity, it is far from that displayed by yatein and podophyllotoxin. These results confirm that demethylation and the introduction of halo substituents diminish the activity of lignans of the dibenzylbutyrolactone type.
Structure‐Activity Relationships in a Series of 8‐Substituted Xanthines as Bronchodilator and A1‐Adenosine Receptor Antagonists
Authors: Corsano Stefano , Strappaghetti Giovannella , Scapicchi Rossana , Lucacchini Antonio , Senatore Generoso 
Published: October 2006

AbstractFour new derivatives of 8‐piperazine ethyl xanthine were synthesized and their bronchospasmolytic activity and A1‐adenosine affinity were studied. Their relaxant action in the tracheal muscle was lower than that of theophylline and that of theophylline derivatives substituted at the 7‐position. Only compound 9, where the methyl group in the 1‐position of the theophylline was substituted by an isobutyl group, shows a good affinity towards the A1‐adenosine receptor.
Structure‐Activity Relationship Studies of CNS Agents, Part 25: 4,6‐Di(heteroaryl)‐2‐(N‐methylpiperazino)pyrimidines as New, Potent 5‐HT2A Receptor Ligands: A Verification of the Topographic Model
Authors: Mokrosz Maria J. , Strekowski Lucjan , Kozak Wei Xing , Duszyńska Beata , Bojarski Andrzej J. , Kłodzinska Aleksandra , Czarny Agnieszka , Cegła Marek T. , Dereń‐Wesołek Anna , Chojnacka‐Wójcik Ewa , Dove Stefan , Mokrosz Jerzy L. 
Published: October 2006

AbstractA series of new 4,6‐di(heteroaryl)pyrimidines containing an N‐methylpiperazino group (6–13) or an ethylenediamine chain (15–20) in position 2 were synthesized and their 5‐HT1A and 5‐HT2A receptor affinities were determined. It was shown that the substituent effects on the 5‐HT2A affinity are additive and could be described quantitatively. In a behavioral model it was also demonstrated that 6–11 are 5‐HT2A receptor antagonists. The molecular modelling results suggested that the distances between the basic nitrogen atom and the two aromatic centers (d1 = 5.2−8.4 Å, d2 = 5.7−8.5 Å, and d3 = 4.6−7.3 Å) define the molecular topography of the 5‐HT2A receptor antagonists under study.
Facile Syntheses of C2‐Symmetrical HIV‐1 Protease Inhibitors
Authors: König Stephan , Ugi Ivar , Schramm Hans J. 
Published: October 2006

AbstractWith the goal of obtaining inexpensive yet potent anti‐AIDS drugs, simple inhibitors of HIV‐1 protease were synthesised. The C2‐symmetrical pseudopeptidic substrate analogues can be prepared as inhibitors for HIV‐1 protease starting from symmetrical ketones 3a–d by a facile four‐step synthesis. After bromination of 3a–d to α,α′‐dibromoketones 4a–d, we synthesised the diamino compounds 6a–c by Gabriel synthesis, which were then coupled with Z‐valine to yield inhibitors with a central keto group 2a–c. We also synthesised inhibitors including a central hydroxy group 8a‐d a‐i by azidation, reduction with LiAlH4 and coupling of the β,β′‐diaminohydroxy compounds with appropriate peptides. The first set of compounds showed only weak inhibition whereas the latter reach Ki values of up to 3.0 μM.
On the Fluorescence Reaction of Pharmaceutically Important 1,3‐Diamines and o‐Aminobenzenesulfonamides with Homophthalaldehyde
Authors: Troschütz Reinhard , Heinemann Oliver 
Published: October 2006

AbstractOn treatment with pharmaceutically important primary 1,3‐diamines 2 and 8 as well as o‐aminobenzenesulfonamides 13–15, homophthalaldehyde (1) yields the intensely blue fluorescent, heteroanellated isoquinolines 5 and 9, as well as moderately fluorescent isoquinobenzothiadiazines 16–18.
Nucleosides and Nucleotides, Part 144 Synthesis and Antiviral Activity of 5‐Substituted (2′S)‐2′‐Deoxy‐2′‐C‐Methylcytidines and ‐uridines[1]
Authors: Awano Hirokazu , Shuto Satoshi , Miyashita Takanori , Ashida Noriyuki , Machida Haruhiko , Kira Toshihiko , Shigeta Shiro , Matsuda Akira 
Published: October 2006

AbstractSynthesis of several 5‐substituted (2′S)‐2′‐deoxy‐2′‐C‐methylcytidines (8) and ‐uridines (6, 11) has been accomplished using radical deoxygenation of the 2′‐tert‐alcohols via their methyl oxalyl esters as a key reaction. Anti‐herpes simplex virus type‐1 and ‐2, and anti‐varicella‐zoster virus activities of the newly synthesized nucleosides were evaluated. Among them, the 5‐iodouracil derivative 6e showed the most potent activity against herpes simplex virus type‐1, with an EC50 of 0.14 μg/mL without showing cytotoxicity up to 100 μg/mL, but had a weak activity against herpes simplex virus type‐2 and no activity against varicella‐zoster virus up to 50 μg/mL in vitro. Although the 5‐fluorocytosine derivative 8b had a potent anti‐herpes simplex virus type‐1 activity (EC50 = 0.22 μg/mL), it was rather cytotoxic to the CCRF‐HSB‐2 human T‐cell line (IC50 ≥ 1.0 μg/mL).
Syntheses and Selective Inhibitory Activities of Terphenyl‐Bisamidines for Serine Proteases
Authors: von der Saal Wolfgang , Engh Richard A. , Eichinger Andreas , Gabriel Bernhard , Kucznierz Ralf , Sauer Jürgen 
Published: October 2006

AbstractBiphenyl nitriles 5a—c, terphenyl dinitriles 11a—d, and naphthalene‐bis(benzonitrile) 11e were prepared by palladium‐catalyzed cross coupling reactions and subsequently converted to biphenyl amidines 8a—c and bis(benzamidines) 4a—e. Among the biphenyl amidines 8 only the meta‐derivative 8b inhibits factor Xa and trypsin (Ki = 10 μM). The terphenyl bisamidine 4c does not inhibit factor Xa, trypsin, thrombin, and plasmin, while 4a and 4d are almost equipotent inhibitors of theses enzymes (Ki 1–6 μM), and 4b and 4e are selective for trypsin (Ki = 0.2 and 0.3 μM; but Ki > 1 μM for factor Xa, thrombin, and plasmin). X‐ray analysis of crystals of 4b complexed with bovine trypsin revealed a unique binding mode: one benzamidino group binds in the S1 site to the side chain carboxylate of Arg189. The central phenyl group is twisted away from the S2/S3 sites and the second amidino group contacts the Asn143 side chain.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, Part 32 Antimicrobial Effects of Oligoamines
Authors: Rehse Klaus , Woyke Christian , Rodloff Arne , Hahn Helmut 
Published: October 2006

AbstractTwenty‐four oligoamines belonging to six (1–6) structurally different types were tested in vitro for their antibacterial activity against 14 different bacterial species comprising a total of 187 strains. Ten compounds were able to inhibit growth of at least one strain at concentrations ⩽10 μmol/L. For three compounds, minimum inhibitory concentrations for some strains were even below 1 μmol/L. Clear structure‐activity relationships showed that the inhibitory effect depended on the bridge connecting the nitrogen atoms, the substitution of the nitrogens, and the number of nitrogen atoms present in one molecule. Substitutions like N‐4‐phenylbutyl, N‐octyl, and N‐nonyl were most active, while short (butyl) and long (dodecyl) substituents diminished or abolished the activity. The antimicrobial spectrum of the oligoamines tested here covered gram‐positive (e.g. Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis) and gram‐negative (e.g. Escherichia coli, Citrobacter spp., Acinetobacter spp.) microorganisms. The type of action was classified as bactericidal. As the inhibition of growth is complete immediately after the addition of the oligoamines, an interaction with the bacterial cell‐membrane is probable.
Tolperisone: Evaluation of the Lidocaine‐Like Activity by Molecular Modeling
Authors: Fels Gregor 
Published: October 2006

AbstractTolperisone (1), a muscle relaxant with lidocaine‐like activity, was compared to lidocaine (2) by molecular modeling methods. Conformational search analysis has been employed to find the global minima of these compounds along with numerous low energy conformations from which specific conformers were extracted that show good superimposition of the structural features important for protein binding. Two additional compounds, mepi‐ (3) and bupivacaine (4), were included in the analysis to validate the method as these ligands show very close structural and pharmacological relationship to lidocaine (2) and are assumed to bind to an identical site. As a result we find conformers of all four ligands that have exactly the same position and orientation of the potential sites for hydrogen bonding with the rest of the molecule showing close comparison of the three‐dimensional geometry. Semiempirical calculations furthermore reveal good agreement of the electrostatic potentials of these conformations indicating similar interactions with a receptor. We conclude that tolperisone (1) and lidocaine (2) despite their chemical divergence can still attach to identical protein binding sites.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, Part 33 From Tetradecane‐ to Octacosanediamines
Authors: Rehse Klaus , Nolte‐Driller Rafaela 
Published: October 2006

AbstractTwenty alkanediamines were designed according to structure‐activity relationships drawn from previous parts of this series and synthesized. Their general structure is CH3‐(CH2)n‐CHNH2‐(CH2)m‐CHNH2‐(CH2)n‐CH3, (n = 2–10; m = 3–6). Twelve of them inhibited the aggregation of human blood platelets in concentrations between 3–10 μmol/L halfmaximally (Born test, inducer collagen). With increasing m a decreasing n is necessary to achieve the optimum activity. In the most active compounds (7b, 7e, 7p) it is found that m + n = 9. When the nitrogen functions are hydroxyalkylated secondary amines with similar antiplatelet effects are obtained. The conversion of the amino groups into sydnonimines is accompanied by the loss of activity. The bisethoxycarbonylderivatives of 7f and 7m (8f, 8m) exhibited antithrombotic effects in rats after oral administration.
Inhibition of Type 4 Cyclic Nucleotide Phosphodiesterase by 8‐Chloroxanthines
Authors: Arch Jonathan R. S. , Buckle Derek R. , Connolly Brendan J. , Faller Andrew , Fenwick Ashley E. , Murray Kenneth J. , Rami Harshad K. , Smallridge Mark S. , Smith David G. 
Published: October 2006

AbstractIn an endeavour to develop isoenzyme selective inhibitors of the cyclic nucleotide phosphodiesterases, structural modifications of 8‐amino‐1,3‐bis(cyclopropylmethyl)xanthine (BRL 61063) have been investigated. Particularly significant was the observation that certain 7‐aralkyl derivatives incorporating chlorine or bromine in place of the 8‐amino substituent afforded selective inhibitors of the PDE 4 isoenzyme. The 7‐(2‐naphthylmethyl) derivatives of 8‐chloroxanthine 16 and 8‐bromoxanthine 17 in particular showed sub‐micromolar IC50 values against PDE 4 while eliciting some 10 and 100‐fold or greater selectivity, respectively, against the 1b, 1c, 2, 3, and 5a isoenzymes.
Synthesis and Antiplatelet Activity of 1‐tert‐Butylamino‐3‐(3‐thienyloxy)‐2‐propanols
Authors: Abdallah Susana , Darias Victoriano , Donoso Rosa , de Urríes Pilar Jordán , Lissavetzky Jaime 
Published: October 2006

AbstractThe synthesis of new 1‐tert‐butylamino‐3‐(3‐thienyloxy)‐2‐propanols by two alternative methods is described. Their initial antiplatelet activity evaluation against ADP, adrenaline, and collagen is reported, and the preliminary structure‐activity relationships are established. The appropriateness of further pharmacological investigations, especially for the best compound of the series 1f, is indicated.