P01 - Rapid Generation Of Polymer-Bound Enones By Microwave-Assisted Solid-Phase Synthesis
Gernot A. Strobmeier, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria

P02 - Synthesis Of Hapalosin Analogs By Solid-Phase Chemistry
Christoph Hermann, Martin E. Maier
University of Tubingen, Institute for Organic Chemistry, Tubingen, Germany

P03 - Effects Of Microwave Irradiation Towards Carbodiimide-Mediated Esterifications On Solid-Phase
Alexander Stadler, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria

P04 - Rapid Homogenous Phase Sonogashira Coupling Reactions Using Controlled Microwave Heating
Mate Erdelyi, Adolf Gogoll
Uppsala University, Dept. of Organic Chemistry, Uppsala, Sweden

P05 - Multidimensional Libraries From Two-Component Heterocyclic Condensations
V. A. Mikhailov, A. L. Kanibolotskii, N. I. Burakov
Institute of Physical Organic and Coal Chemistry, Donetsk, Ukraine

P06 - Variations Of The Biginelli Multicomponent Reaction Using Methyl 4-Chloroacetoacetate
Tetyana Beryozkina, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria

P07 - Synthesis Of New Sterol-Spermidine Conjugates With Potential Antimicrobial Activity
Khaled Shawakfeh
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan

P08 - Solid-Phase Synthesis Of Biofunctional 4-Aryl-3,4-Dihydropyrimidin-2(1 H) -ones
Doris Dallinger1, Maria Garcia Valverde2, C. Oliver Kappe 1
1Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria
2Dept. of Chemistry, Area of Organic Chemistry, University of Burgos, Burgos, Spain

P09 - Synthesis Of New Bis-Steroids And Selective Catalytic Oxidation Of Dimeric Steroids
Kbaled Shawakfeh, Ahmad A1-Ajloui, Abdelatif Jbdah
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan

P10 - Generation Of High-Loading Resin Beads For Single Bead Screening Using Solid-Phase Dendrimer Chemistry
Sylvain Lebreton
University of Southampton, Southampton, United Kingdom

P11 - Polymer Supported Diazonium Salts
James Merrington
University of Southampton, Southampton, United Kingdom

P12 - Enantioselective Synthesis Of A Small Combinatorial Library Of Resin Linked Steganone Analogues With Potential Anutumor Activity
Erik Van der Eycken, Liesbeth Stoffels
Laboratoiy for Organic Synthesis, Catholic University of Leuven, Heverlee, Belgium

P13 - Design Of Multielectrode Arrays For High-Throughput Impedance Screening Of Novel Gas Sensor Materials
Ulrich Simon, Daniel Sanders, Jorg Jockel, C. Heppel
Institute of Inorganic Chemistry, Aachen University of Technology (RWTH), Aachen, Germany

P14 - Thioamides As Building Blocks To Prepare Libraries Of New Sulfur Containing Heterocyclic Compounds
Vasiliy Bakulev, Natalia Belskaia, Yury Morzherin, Maria Kosterina, Igor Paramonov
TOS Lab, The Urals State Technical University, Ekaterinburg, Russia

P15 - Combinatorial And Conventional Development Of Novel Dehydrogenation Catalysts
Jörg Urschey1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany

P16 - Combinatorial Synthesis And Investigation Of New High-Temperature Combustion Catalysts
T. Wolter1, Jens Klein1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany

P17 - High-Throughput Spatially Resolved MS And GC For The Screening Of Heterogeneous Catalysts
Pierre-Alain Weir1, Matthias Orschel1, Jens Klein1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany

P18 - Combinatorial Synthesis Of New Mixed Metal Oxides For Catalysis Via Sol-Gel Route And First High.Troughput And Convenyional Tests
Daniel Klär1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrücken, Germany

P19 - Materials Discovery By Computer Aided Library Design
Guido Kirsten1, W. Ben Mustapha1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrllcken, Germany

P20 - Combinatorial And Conventional Development Of Novel Catalysts For Lowtemperature Co Oxidation
Jens W. Saalfrank1, Guido Kirsten1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany

P21 - Combinatorial Synthesis And Automated Characterisation Of Optical Gas Sensors
Athanasios Apostolidis1, Ingo Klimant2, Jane Lewis3, Darnian Andrzejewski', Otto S. Wolfbeis 1
1lnstitute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Regensburg, Germany
2lnstitute of Analytical Chemistry, University of Technology, Graz, Austria
3University of Wales, Swansea, Wales, United Kingdom

P22 - Mg(II) Catalysed Asymmetric 1,3-Dipolar Cycloadditions On Solid Support
Fabio Rancati1, Giuseppe Faita1, Paolo Quadrelli', Alfredo Paio2, Pierfausto Seneci3 1University of Pavia, Pavia, Italy
2Glaxo SmithKline Group, Verona, Italy
3NAD, Munich, Germany

P23 - Barium Magnesium Tantalate Thin Films Obtained By Sol-Gel: An Application Of HTE To High Frequency Dielectrics
Virginie Rouaux1, Frank Jermann1, Wilhelm F. Maier2, Olivier Guillou3
1Siemens AG, München, Germany
2University of the Saarland, Saarbrucken, Germany
3INSA, RENNES, France

P24 - Sulfated Peptides As Heparin Mimics Designed For FGF Receptors
Socorro Vázquez Campos, Morten Meldal
Carlsberg Research Centre, Copenhagen, Denmark

P25 - Intramolecular Cyclization Using Solid Phase Heck Reaction
Kenichi Akaji, Saburo Aimoto
Institute for Protein Research, Osaka University, Suita, Japan

P26 - General Combinatorial Synthesis Of Tertiary Amines On Solid Support
Magnus Gustafsson, Roger Olsson, Carl-Magnus Andersson
Acadia Pharmaceuticals A/S. Glostrup, Denmark

P27 - An Efficient And Convergent Route Towards Water-Soluble, Chiral And Amphiphilic Macrocyles
Tapes Bhattacharyya, Ulf J. Nilsson
Lund University, Lund, Sweden

P28 - Novel Chiral Salicylic Aldehydes: Chiral Building Blocks For Combinatorial Synthesis
Albrecht Berkessel, Matthias Vennemann, Alexander H. Vetter
Department of Organic Chemistry, University of Cologne, Cologne, Germany

P29 - Synthesis Of A Novel Diamino-Anthracene Derivative And Its Conjugation With A Panel Of Amino Acids Building Blocks For Artificial Receptors
Sumita Bhattacharyya, Ulf 1. Nilsson
Lund University, Lund, Sweden

P30 - Solid-Phase Synthesis And Screening Of A Sulfahydantoin Library
Javier Garcial, Fernando Albericiol, Lois M. Bryman2, Ennque L. Michelotti2, Ernesto Nicolás1, Cohn M. Tice2
1Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
2Rohm & Haas Company, Spring House, USA

P31 - Design And Synthesis Of A Spiropiperidine Template Library
S. Cameron, Avril Robertson, S. Gussregen, D. MacManus, M. Allen
Tripos Receptor Research Ltd, Bude, Cornwall, United Kingdom

P32 - A New Highly Efficient Strategy For Generation Of Indan Scaffolds Via A One-Pop Annulation Reaction
Anna Bengtson, Mats Larhed, Anders Hallberg
Uppsala University, Uppsala, Sweden

P33 - Synthesis Of Combinatorial Libraries Of PNA -Conjugates With Metal Complexes For Sequence-Specific Hydrolysis Of Oligonucleotides
Andriy Mokhir, Roland Kraemer
Ruprecht Karls University, Heidelberg, Germany

P34 - Solid Supported Synthetic Equivalents Of 3-Formylchromones And Chromones: Synthesis And Uses In Combinatorial Chemistry
Jose 1. Borrell1, Jordi Teixidó1, Elisabeth Schulerl , Enrique L. Michelotti 2
1Sarria Chemical Institute, Barcelona, Spain
2Rohm and Haas Company, Spring House, PA, USA

P35 - New High Speed Heck Coupling Reactions Assisted By Microwave Flash Heating
Karl S. A. Vallin1, Qisheng Zhang2, Dennis P. Curran2, Mats Larhed1, Anders Hallberg'
1Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden
2Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA

P36 - Solid-Phase Synthesis Of Carbamates, Carbonates And Ureas Using Spot Method
Katrin Michaelis, Norbert Zander, Ronald Frank
GBF Braunschweig, Braunschweig, Germany

P37 - Synthesis For N-Alkoxybenzimidazole Libraries
John M. Gardiner
Univeristy of Manchester (UMJST), Manchester, United Kingdom

P38 - Combinatorial Solid-Phase Synthesis Of A 4(3H)-Quinazolone Library
Csaba Wéber, Attila Bielik, Gyorgy M. Keseru, Gyorgyi I. Szendrei, Istvdn Greiner
Gedeon Richter Ltd., Budapest, Hungary

P39 - Use Of Combinatorial Chemistry To Develop Photocurable Termoplastic Polyurethane Elastomers (Tpus)
Jaume Heras, José L. Falcó, Salvador Borrós, Jose I. Borrell, Santiago Nonell, Emma Polo Sarria Chemistry Institute, Barcelona, Spain

P40 - Solution-Phase Synthesis Of A Library Of Cyclic Tetraalkylammonium Derivatives
Angel Messeguer, Isabel Masip
Department of Biological Organic Chemistry, IIQAB, CSJC, Barcelona, Spain

P41 - Cyclic Pentapeptide Metal Ion Complexation: A Model Of The Binding Unit Of The Prion Protein
Maria C. Alcaro, Mario Chelli, Mario Ginanneschi, Anna M. Papini
University of Florence, Firenze, Italy

P42 - Parallel Solid Phase Synthesis Of Lipophilic Amino Acids
Maria C. Alcaro, Anna M. Papini, Mario Chelli
University of Florence, Firenze, Italy

P43 - Enamine Chemistry In Constructing Diverse Libraries For Screening
Kostyuk Aleksandr
Institute of Organic Chemistty, Kiev, Ukraine

P44 - Combinatorial Library Of 2-Acylmethylbenzoazaheterocycles Transformations Products
Andrei Tolmachev1, Sergei Pipko 2
1lnstitute of Organic Chemistry, Kiev, Ukraine
2lnstitute of Organic Chemistry, National Academy of Science Ukraine, Kiev, Ukraine

P45 - Combinatorial Chemistry With Natural Products As Templates
Alejandro G. Hernanl, Ralf Thiericke2, Susanne Grableyl
1Hans Knoll Institute for Natural Products Research, Jena, Germany
2CyBio Screening GmbH, Jena, Germany

P46 - Combinatorial Derivatization Of Nortropin
Alejandro G. Hernan1, Ralf Thiericke2, Susanne Grabley I
1Hans Knoll Institute for Natural Products Research, Jena, Germany
2CyBio Screening GmbH, Jena, Germany

P47 - Exploring The Substituted Guanidine Moiety As A Pharmacophore Group
Miriam Royo1, Montserrat del Fresno1, Guillermo Gerona2, Rosario González-Muniz3, Antonio Ferrer-Montiel4, Fernando Albericio1, Carolina Garcfa-Martfnez4
1Department of Chemistry, University of Barcelona, Barcelona, Spain
2Department of Chemistry, University of Barcelona; Institute of Medical Chemistry, Madrid, Spain
3lnstitute of Medical Chemistry, Barcelona, Spain
4Center of Molecular and Cellular Chemistry, Miguel Hernández University, Elche, Alicante, Spain

P48 - Imidazoles Catalyze The Oxidation By Organic Peroxides
Ahmad Al-Ajlouni, Khaled Shawakfeh, Lina Al-Quaisi
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan

P49 - Combinatorial And Structure-Based Modifications Of The Vancomycin Antibiotic Core Structure
Christopher J. Arnusch, Roland J. Pieters
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands

P50 - Towards A Synthetic Glycosidase With Combinatorial Chemistry
Jurgen Van Holen, Johan Van der Eycken
Laboratory for Organic and Bio-organic Synthesis, Ghent University, Gent, Belgium

P51 - Combinatorial Synthesis Of Diazo-Dyes: A Student Experiment
Ulrich Jordis, Matthias Treu, Manfred Hirnschall
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria

P52 - A Simple And Economic Design For A Personal Synthesizer
Ulrich Jordis
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria

P53 - Adhesives and Polymers on the Fast Track
Holger Wildt, Helmut Blum, Ilona Lange, W. -D Herberg
Henkel KgaA, Dusseldorf, Germany

P54 - Automated, High Throughput Parallel Synthesis: Multi-Step Solution Phase Chemistries On The Trident Automated Platform
Mike Davies
Argonaut Technologies, Muttenz, Switzerland

P55 - Novel Heterocyclic Libraries
Tatiana A. Smirnova, E. Svetrova, Alexander Bass, Pavel Kurapov, Eugene Babaev
Chemistry Department, Moscow State University, Moscow, Russia
Contribution from Combinatorial Chemistry Center (scientific and educational subdivision of Chemistry Department of Moscow State University).

P56 - JKlustor- Software Tools For Clustering
Ferenc Csizmadia, András Volford
ChemAxon Ltd., Budapest, Hungary

P57 - A Library Of Indolylalkylamines As Building Blocks For Synthesis Of Pharmacologically Active Compounds
Eugene Zakurdaev, Elizabeth Balenkova, Andrew Gavryushin, Valentine Nenajdenko Chemistry Department, Moscow State University, Moscow, Russia

P58 - Monitoring Of Solid Phase Reactions By Ft-Ir And Ft-Raman Spectroscopy
Orsolya Egyed
Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary

P59 - Solution Phase Synthesis Of Pyrrolol2,3-Dipyrimidines
Svetlana V. Kluchko, Victor I. Gorbatenko, Vladimir N. Fetyukhin
I.E. LAB Ltd., Kiev, Ukraine

P60 - Synthesis And Evaluation Of A Split Mix Library Of Synthetic Receptor Molecules
Menno C. F. Monnee, Arwin 1. Brouwer, Rob M. J. Liskamp
Utrecht University, Utrecht, Netherlands

P61 - New Heterocyclic Scaffolds Containing The 2.Fluoronitrophenyl Moiety
Alexandr Ivachtchenko, Alexandr Khizhan
Chemical Diversity Labs, Inc., San Diego, USA

P62 - Design Of Focussed Libraries Using "Bioanalogous' Transformation Rules Implemented To An Expert System (EMIL)
Akos Papp1, Toshio Fujita 2 , Ferenc Darvas 1
1 Comgenex, Inc., Budapest, Hungary
2 EMIL Systems, Kyoto, Japan

P63 - ExclusiveDirect; A Novel e-CRM Tool
János Gerencsér, Gábor Pôcze, Akos Papp, Peter Arva, Adam Kotsis, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary

P64 - HT Work-Up And Purification Technology Supported By Physicochemical Modelling
Agota Bucsai, Akos Papp, Gábor Pôcze, Lajos Godorházy, Ferenc Kálmán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary

P65 - The Development Of A Web Based Client System For Outsourcing Drug-Like Molecules And Bioinformatic Data
Peter Arva, Adam Kotsis, Gábor Pöcze, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary

P66 - Site Distribution In Resin Beads As Determined By Confocal Raman Spectroscopy
Jurgen Kress, Abigail Rose, Jeremy G. Frey, William S. Brocklesby, Geoff W. Mellor, Mark Ladlow, Mark Bradley
University of Southampton, Southampton, United Kingdom

P67 - Polymer-Bound HOBt: Use As Additivein Coupling Reactions And As Support For Protecting Group Transfer
Sophie Barthelemy, Paternuosto Marquis
Calbiochem-Novabiochem AG, Ldufelfingen, Switzerland

P68 - Novel Pyridinium Cationic Linkers For Solid Phase Synthesis
Sweta Ladwa
Loughborough University, Loughborough, United Kingdom

P69 - Marker Libraries: Facing The Challenge Of Chemical Genomics
György Dormán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary

P70 - Combinatorial Discovery Of New Thermal Rearrangement Pathways For Library-From-Library Approaches
Tamás Nagy, Tamás Karancsi, Gydrgy Dormán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary

P71 - High Throughput Synchrotron X-Ray Micro-Characterization
Eric D. Isaacs
Bell Laboratories, Murray Hill, NJ, USA

P72 - An Improved Design Of A Parallel Synthesis Block
Ulrich Jordis
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria

P73 - Combinatorial Libraries Of Benzimidazo[1,2-C]-6(5H)-Quinazolines
Alexandre Ivachtchenko, Sergey Kovalenko, Alexandre Drushlyak
Chemical Diversity Labs, Inc., San Diego, CA, USA

P74 - Relationship Between Hydrophobicity and Antiproloferative Activity of Carboxamids Determined by Chromatographic Methods and MTT Assay
Ferenc Hollosy1, Janos Seprodi1, D. Eros2, L. Orfi2, Gyorgy Keri1 Miklos Idei1
1 Semmelweis University Budapest, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Hungary;
2 Institute of Pharmaceutical Chemistry, Budapest, Hungary

P75 - Synthesis of 3-Alkyl(Aryl)-5-(Alkylsulfanyl)[1,3]Thiazolo[4',5':4,5]Pyrimido-[1,6-/l]Benzimidazole-2(3/i)-Thiones
Alexandre Ivachtchenko, Sergey Kovalenko, Alexey Parkhomenko
Chemical Diversity Labs, Inc., San Diego, CA, USA,

P76 - Combinatorial Libraries of Condensed Heterocycles Containing the 2-Mercapto-4 (3 H) -Pyrimidinone Fragment
Alexandre Ivachtchenko, Sergey Kovalenko, Alexey Ilin, Alexandr Drushlyak
Chemical Diversity Labs, Inc., San Diego, CA, USA;

P77 - New Scaffolds Containing the Quinoline-6-Sulphonamide Moiety for Combinatorial Synthesys
Alexandre Ivachtchenko, Vladimir Kobak
Chemical Diversity Labs, Inc., San Diego, CA, USA

P78 - Antimicrobial proteins produced by microorganisms, a perspective for food preservation
Le Thanh Binh
Institute of Agricultural Genetics, Conhue, Tuliem, Hanoi, Vietnam

P01 - Rapid Generation Of Polymer-Bound Enones By Microwave-Assisted Solid-Phase Synthesis
Gernot A. Strobmeier, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria
Reaction speed is generally recognized as an important factor in high-throughput solid-phase and combinatorial synthesis. Here we report on examples of high-speed solid-phase organic synthesis carried out by microwave irradiation, which is emerging as a powerful new technology. A rapid and efficient two step synthesis of polymer-bound enones utilizing flash heating by microwave irradiation is presented. In the first step various acetoacetates are attached to Wang resin by microwave-promoted transesterification of their methyl or ethyl esters. Compared with conventional thermal procedures (110°C), reaction times were dramatically reduced from 6-18 hours to 5-10 minutes.
The second step involves a Knoevenagel condensation of the polymer-bound acetoacetates with aromatic aldehydes using piperidine acetate as catalyst. In contrast to the classical, thermal protocol (80°C) complete conversion was observed within 30-60 minutes under microwave irradiation, which constitutes a significant acceleration compared to the 24-72 h required using conventional heating.
Efficient absorption of microwave irradiation, excellent swelling properties for polystyrene-based resins and inertness under the reaction conditions are the requirements for the choice of solvent for these transformations. All reactions were performed in a purpose-built multimode microwave cavity with on-line temperature measurement and microwave power control, that can be readily adapted to a high-throughput parallel synthesis format.

P02 - Synthesis Of Hapalosin Analogs By Solid-Phase Chemistry
Christoph Hermann, Martin E. Maier
University of Tubingen, Institute for Organic Chemistry, Tubingen, Germany
In this presentation we illustrate the synthesis of a small library of analogs of the depsipeptide hapalosin. The 12-membered macrocycles are characterized by one ester and two amide bonds. They are assembled from three building blocks, a beta-hydroxy acid, an alpha-amino acid, and an unusual ganuna-amino-beta-hydroxy acid. As protecting groups the Fmoc- for the amino function, and the THP-group for the hydroxy function proved to be advantageous.
The solid-phase assembly started with the attachment of the beta-hydroxy acid to the Wang resin. After removal of the THP-group the Fmoc-protected gammna-amino-beta-hydroxy acid was attached. This was followed by deprotection of the amino group followed by condensation with an alpha-amino acid. The assembled cyclization precursor was removed from the resin, purified, and deprotected. Macrolactamization gave the analogs. Diversity was established by Evans aldol reactions to produce syn-beta-hydroxy acids and by using different alpha-amino acids. The general strategy should be useful for the synthesis of other biologically active cyclic depsipeptides.


P03 - Effects Of Microwave Irradiation Towards Carbodiimide-Mediated Esterifications On Solid-Phase
Alexander Stadler, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria
One of the most common solid-phase reactions in combinatorial synthesis involves the coupling of an acid (i.e. an amino acid) to polystyrene solid supports (i.e. Wang resin). A number of publications have reported the coupling of various acids using carbodiimide either via the isourea method or the symmetrical anhydride method. Since the reaction times at ambient temperature have been reported to be rather long (16-48 h) we have investigated the effects of microwave irradiation towards this reaction. As a model case we have studied the esterification of polymer-supported alcohol (Wang resin) by benzoic acid derivatives in the presence of catalytic amounts of DMAP. 1 Tn the microwave-assisted solid-phase coupling via the O-acylisourea method the main product was 1-benzoyl-1,3-diisopropylurea, formed by rearrangement of the thermolabile isourea. (Scheme 1) On the other hand significant rate enhancements were observed for the coupling of benzoic anhydride using microwave flash heating in 1-methyl-2-pyrrolidone as a solvent. Reaction times were reduced from 2-3 days to 10 mm by microwave dielectric heating.


P04 - Rapid Homogenous Phase Sonogashira Coupling Reactions Using Controlled Microwave Heating
Mate Erdelyi, Adolf Gogoll
Uppsala University, Dept. of Organic Chemistry, Uppsala, Sweden
Using combinatorial methods fast preparation of a large variety of chemical entities is possible today. The automatisation of parallel synthesis, purification and analysis of the products is the source of the high speed of this method. However, the effectiveness is still limited by the rate of chemical reactions. One attempt to make further improvements would have to address this weakness in drug discovery. Arylalkynes, the products of the Sonogashira coupling reaction, are interesting intermediates for the preparation of a variety of target compounds. Recent examples include heterocyclic compounds, molecular scale electronic devices, cyclophanes, estradiol derivatives, enediyne antibiotics, and natural products with antitumor or phytotoxical activity. A microwave-enhanced, rapid and efficient homogenous phase version of the Sonogashira reaction is presented here. It has been applied to the coupling of aryl iodides, bromides, triflates and one aryl chloride. The generality of the method is demonstrated for the reaction of trimethylsilyl acetylene with homoaromatic, pyridine and thiophene derivatives. Excellent yields (80-95%) for substrates containing a large variety of substituents in different positions are obtained in 5-25 minutes. Using the Smith Synthesiser, the microwave enhanced procedure can be automated

P05 - Multidimensional Libraries From Two-Component Heterocyclic Condensations
V. A. Mikhailov, A. L. Kanibolotskii, N. I. Burakov
Institute of Physical Organic and Coal Chemistry, Donetsk, Ukraine
Multidimensional library construction opens wide possibilities in creating of new chemical entities from limited number of starting materials and synthetic schemes. It is obvious that if three- or more components may be involved in structure formation, three- or more dimensional libraries may be obtained using the only one synthetical procedure. But the same results may be gained using simple two-component heterocyclic condensations, provided that at least one component is built of two (or more) variable fragments. Some examples have been demonstrated.


P06 - Variations Of The Biginelli Multicomponent Reaction Using Methyl 4-Chloroacetoacetate
Tetyana Beryozkina, C. Oliver Kappe
Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria
Complexity-generating/diversity-oriented high throughput synthesis of druglike compounds and libraries thereof has been a focus in the arsenal of combinatorial synthesis. Being capable of combining three or more reactants together in a single ordered event, multicomponent reaction (MCRs) exemplified by the Ugi 4CR or Biginelli 3CR offer great possibility for molecular diversity per step and are becoming a cornerstone of combinatorial synthesis. In the Biginelli dihydropyrimidine synthesis, an aldehyde, (thio)urea, and 1 ,3-dicarbonyl compound are condensed together in acidic medium to produce a multifunctionalized dihydropyrimidine scaffold (DHPMs). In order to expand the structural diversity of interesting scaffolds that can be generated using Biginelli-type MCRs we are currently exploring combinations of Biginelli- with other types of reactions, often in a one-pot format.
Here we report on a variation of this MCR, using commercially available methyl 4-chloroacetoacetate as building block. The resulting 6-chioromethyl-functionalized DHPMs 1 serve as starting materials for the generation of a variety of interesting drug-like heterocyclic scaffolds, such as furo[3,4-d]pyrimidines, pyrrolo[3,4-d]pyrimidines, and pyridazino[4,5-d]pyrimidines.


P07 - Synthesis Of New Sterol-Spermidine Conjugates With Potential Antimicrobial Activity
Khaled Shawakfeh
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan
New sterol-spermidine conjugates were synthesized by reductive amination of the ketone of the C-3 position of stigmasterol 3, 6-oxostigmasterol 9, 7a,12a-dihydroxy-3-oxo-5b-cholanic acid methyl ester 15, and at the C-22 position of
3-oxopregn-4-ene-20b-carboxaldehyde 19, with various polyaimnes using sodium triacetoxyborohydride as a reducing agent. We have synthesized a number of structures that incorporate readily available steroids with spermidine functionality at C-3 as in squalamine. In order to increase hydrophilicity, steroids with increasing numbers of hydroxyl groups were used. We have also attached spermidine at the C-22 position of a steroid. These compounds showed potent antimicrobial activity.

P08 - Solid-Phase Synthesis Of Biofunctional 4-Aryl-3,4-Dihydropyrimidin-2(1 H) -ones
Doris Dallinger1, Maria Garcia Valverde2, C. Oliver Kappe 1
1Karl Franzens University, Institute of Chemistry, Organic and Bioorganic Chemistry, Graz, Austria
2Dept. of Chemistry, Area of Organic Chemistry, University of Burgos, Burgos, Spain
4-Aryl-3,4-dihydro-2(1H)-pyrimidone esters (DHPM5) represent a heterocyclic system of remarkable pharmacological efficiency. I In recent years properly functionalized DHPMs have emerged as calcium channel blockers, antihypertensive agents, ala-adrenergic antagonists, and neuropeptide Y (NPY) antagonists. Particular interest has been devoted to orally active antihypertensive DHPMs such as SQ 32,926 and related derivatives. 1 We are currently developing a solid-phase protocol for the synthesis of structurally diverse DHPM derivatives that is outlined below. Our strategy is based on a solid-phase adaption of the classical Biginelli cyclocondensation reaction, involving the treatment of polymer-bound B-ketoesters with aromatic
aldehydes and (thio) urea. Synthetic details and alternative strategies for the synthesis of DHPMs will be described.


P09 - Synthesis Of New Bis-Steroids And Selective Catalytic Oxidation Of Dimeric Steroids
Kbaled Shawakfeh, Ahmad A1-Ajloui, Abdelatif Jbdah
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan
New dimeric steroids were synthesized by reductive amination of the aldehyde of 3-oxopregn-4-ene-20b-carboxaldehyde and the ketone of stigmasterol and cholesterol, with 1 ,3-diaminopropane, 1 ,4-diaminobutane and 1 ,6-diaminohexane using sodium triacetoxyborohydride as reducing agent. The catalytic oxidation of the double bond in these dimeric steroids by CH3ReO2-H202 system were studied and showed that stigmasterone were selectively epoxidized on the internal double bonds without affecting the external one. The final products were characterized as 1 ,2-diols. A mechanism in which the Re-peroxide species transfer an oxygen to the steroid double bond has been proposed.


P10 - Generation Of High-Loading Resin Beads For Single Bead Screening Using Solid-Phase Dendrimer Chemistry
Sylvain Lebreton
University of Southampton, Southampton, United Kingdom
The process of split and mix synthesis is perhaps one of the most powerful methods of generating large compound numbers both in terms of synthetic efficiency, cost effectiveness per compound and also speed. The process of split and mix synthesis by its very nature also produces compounds in such a way that there is a single compound attached to a single resin bead. The issue then becomes one of utilising this synthetic tool in a screening sense. This method is potentially very powerful but suffers from limited amounts of compound on single beads and the associated need for a tagging or decoding strategy. One way to overcome these limitations is to enhance bead loading by a process termed dendrimerisation. This method is based on the controlled growth of dendrimers on solid phase via stepwise reiterative reactions leading to an exponential increase in the number of reactive sites.
We have synthesised a number of symmetrical 1*3 C-branched isocyanate-type monomers for their evaluation as a means of loading enhancement. Using these monomers we have generated beads with a loading >100 nmoles, which should be sufficient for structure characterisation and several screening assays from single beads. These dendrimer-based beads will be used to prepare small libraries for screens in the area of infectives.

P11 - Polymer Supported Diazonium Salts
James Merrington
University of Southampton, Southampton, United Kingdom
The development of polymer supported reagents for use in solution phase synthesis allowed an azo dye library (6x6) to be generated, using a novel diazonium salt loaded ion-exchange resin.

P12 - Enantioselective Synthesis Of A Small Combinatorial Library Of Resin Linked Steganone Analogues With Potential Anutumor Activity
Erik Van der Eycken, Liesbeth Stoffels
Laboratoiy for Organic Synthesis, Catholic University of Leuven, Heverlee, Belgium
During the last decade, solid-phase synthesis and combinatorial technologies have gained considerable interest, as this
methodology has been proven to be a powerful tool in the synthesis of large numbers of analogues of an interesting lead compound. The aim of our project is to transfer our experience in the field of the total synthesis of natural products and pharmaceuticals to the synthesis on a solid support. Therefore we have chosen to embark on the synthesis of a small library of steganone analogues, which will also be screened on their potential antitumor activity.
Steganone and steganacin are two bisbenzocyclooctadiene lignan lactones isolated and characterized by the late S. M. Kupchan. Steganacin and the unnatural stegane have displayed significant activity in vivo against P-388 leukemia in mice and in vitro against cells derived from carcinoma of the nasopharynx (KB). Therefore these compounds have continued to be a popular target through the last two decades. Many synthetic studies have been conducted on these compounds and structure-activity relationships have been investigated. To date nine total syntheses of steganone and analogues have been achieved [2]. Although a lot of research has been devoted to this target, the number of synthesized analogues is rather limited. Moreover, to the best of our knowledge, nobody has ever tried out the synthesis of this class of compounds on a solid support. Nevertheless, solid-phase synthesis could be extremely useful for the construction of the macrocyclic ring of these compounds (dilution principle ?). Therefore the development of a combinatorial library of steganone analogues via solid phase synthesis appears to be an interesting research object. As a "lead" compound, we will focus our attention to 7-aza-analogues: indeed, nitrogen is isosteric to carbon in many cases, and our choice has the particular advantage to simplify the synthesis, as we do not have to deal with control of stereochemistry at C7. The synthesis of some 7-aza-analogues, displaying enhanced activity, has already been described by K. Koga [3], albeit not on a solid support. The proposal follows the main guidelines for the synthesis on a solid support. Nevertheless, the application of solid-phase chemistry to this class of target molecules is fully new, and constitutes an interesting synthetic challenge!

P13 - Design Of Multielectrode Arrays For High-Throughput Impedance Screening Of Novel Gas Sensor Materials
Ulrich Simon, Daniel Sanders, Jorg Jockel, C. Heppel
Institute of Inorganic Chemistry, Aachen University of Technology (RWTH), Aachen, Germany
Complex low-frequency impedance spectroscopy (IS) is one of the most suitable and common tool to study the electrical properties of electronic, ionic, or mixed electronic/ionic conductors, which have potential applications in e.g. catalysis, energy storage or chemical sensing. IS has evolved to an important method of characterisation within the field of materials sciences, and is, if compared to other methods, a very rapid and at the same time relatively inexpensive tool. Applied over a broad temperature and frequency range it allows to distinguish between charge transport and polarisation phenomena in the bulk or at the interfaces of a electrode/material system and thus could successfully be applied to analyse the physicochemical properties, e.g. of gas sensing elements.
However, up to now IS mainly was restricted to sequential characterisation of materials. In this work we report for the first time on the design of multielectrode arrays for high-throughput impedance screening of novel sensor materials. We will introduce the design rules for the electrode layout in an array of inter digital capacitors and we will discus the effect of structural variation as well as methods to eliminate parasitic effects; like stray capacitances or contact resistances. A multielectrode array with 64 interdigital capacitors in a 8x8 arrangement will be presented.
This is suitable for high temperature (1000K) high throughput impedance screening of sensor materials, applied by automated direct synthesis or by screen printing techniques to the electrode wells. This makes IS available for combinatorial research on the electrical properties of novel solid materials of various composition.

P14 - Thioamides As Building Blocks To Prepare Libraries Of New Sulfur Containing Heterocyclic Compounds
Vasiliy Bakulev, Natalia Belskaia, Yury Morzherin, Maria Kosterina, Igor Paramonov
TOS Lab, The Urals State Technical University, Ekaterinburg, Russia
Thioamides are the class of organic compounds that is of paramount importance in the synthesis of sulfur containing heterocyclic compounds. Thiophenes, thiazoles, isothiazoles, thiadiazoles, thiopyranes, thiopyridones, thiadiazepines and many other heterocycles can be prepared based on the reactions of thioamides with electrophilic reagents.
Recently we have prepared new 2,5-dimethylenethiazol-4-one derivatives by the reaction of malon thioamides with dimethyl acetylene dicarboxylic acid (DMDA). Now we report two novel approach to thiazoles and thiophenes bearing in
molecule exocyclic double bonds. First one based on the reaction of thioamides with chloroacetic ester followed by condensation with aldehydes to final thiazoles. Another one included the new reaction of thioamides of type with DMDA to give thiophenes.
Solution phase methodologies were used to prepare in TOSLAB libraries of sulfur containing heterocyclic compounds and

P15 - Combinatorial And Conventional Development Of Novel Dehydrogenation Catalysts
Jörg Urschey1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany
Our strategy to find new catalysts for gas-phase dehydrogenation reactions is presented. In a first high-throughput screening phase more than 500 materials have been tested for catalytic activity employing JR-Thermography. Selected active substances have been synthesized on a larger scale (several grams) and subjected to conventional testing in a fixed bed reactor system and _ GC product analysis. The best catalyst was then used to optimize reaction conditions with the help of a factorial design. The large amount of data generated by this process was analysed by employing software based data-mining techniques.

P16 - Combinatorial Synthesis And Investigation Of New High-Temperature Combustion Catalysts
T. Wolter1, Jens Klein1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany
Materials with a temperature stable large surface area are essential for combustion catalysis. All conventional catalysts suffer from poor temperature stability (sintering). The sintering process is influenced by several factors: The diffusion coefficient, the tendency to aggregate, the form of packing and the number of contact points. In a combinatorial study we have searched for new porous mixed oxides with superior thermal stability. To increase the thermal stability two approaches were tested: doping with metal ions changes the chemical environment and hampers phase transitions and using multi phase systems with inferior solubility among each other leads to different particle sizes and a minimization of contact point. Mixed oxides of Si02, Ti02, Zr02 and A1203 have been prepared and tested and two mixed oxides showed a stable porosity at temperatures 1 1000C. The most stable mixed oxides were than doped with 60 different elements on combinatorial libraries and tested for catalytic activity. The heat of reaction of the combustion of isooctane, n-butane and methane with synthetic air, detected by emissivity corrected JR-thermography, was used as indicator for catalytic activity. New catalysts free of noble metals have been identified, which catalyse the combustion of methane at temperatures than lower 2000 C.

P17 - High-Throughput Spatially Resolved MS And GC For The Screening Of Heterogeneous Catalysts
Pierre-Alain Weir1, Matthias Orschel1, Jens Klein1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany
Recent developments in the high-throughput synthesis of heterogeneous catalysts lead to the necessity for fast screening methods. Our existing technique for spatially resolved MS has been improved significantly. The central part of the new set-up is a capillary bundle ending in a steel syringe, that is moved by a robot and enters the library compartments sequentially. All capillaries are heated by heating wires and thermally insulated to avoid condensation, while high flexibility and breaking strength are given. The gaseous and liquid reagents enter the educt capillary via a preheating and mixing chamber. The heated gas overflows the catalyst sample and the resulting product gas mixture is sampled by separate capillaries, which serve two devices simultaneously. For online measurements, a sector-field mass spectrometer with high mass resolution or high sensitivity and a gas chromatograph with cold injection system for further enhanced sensitivity are attached. For faster measurements, the GC-system analyses one gas sample, while the next one is already being trapped. The measurement time is in the order of I to 2 minutes per catalyst with the MS and between 2 and 10 minutes for GC, depending on the chromatographic retention times.

P18 - Combinatorial Synthesis Of New Mixed Metal Oxides For Catalysis Via Sol-Gel Route And First High.Troughput And Convenyional Tests
Daniel Klär1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrücken, Germany
Combinatorial sol-gel synthesis is an important path to new oxide materials for heterogeneous catalysis and sensor applications. In contrast to other synthesis methods the gelation of a homogeneous sol provides mostly amorphous, porous and transparent mixed oxides with a homogeneous distribution of the containing elements. Catalyst libraries composed of doped indium oxide, gallium oxide, iron oxide and different mixtures of them have been prepared by automated sol-gel-synthesis. The catalytic activity for selective oxidation of hydrocarbons with air has been identified by emissivity corrected JR-thermography. Lead compounds have been identified, prepared and tested under conventional reaction conditions.

P19 - Materials Discovery By Computer Aided Library Design
Guido Kirsten1, W. Ben Mustapha1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrllcken, Germany
By application of high-throughput materials synthesis with 60 elements a 60 dimensional search-space is available. Even with high-throughput experimentation this searchspace cannot be searched in a systematic way. The usage of evolutionary algorithms is one of the most promising ways to surround this problem. The concept is demonstrated by the catalyst development for CO-oxidation in an experiment based on starting library. By selection of a suitable starting point and a sophisticated fitness function the discovery and the optimisation of catalysts can be fully automated in the close future.

P20 - Combinatorial And Conventional Development Of Novel Catalysts For Lowtemperature Co Oxidation
Jens W. Saalfrank1, Guido Kirsten1, Wilhelm F. Maier2
1Max Planck Institute of Coal Research, Mülheim an der Rurh, Germany
2University of the Saarland, Saarbrucken, Germany
CO oxidation at low temperatures is of importance for respiratory protection devices, exhaust gas cleaning and fuel cell technologies. Combinatorial methods have been used to identify novel active materials in a short time. Mixed oxides prepared by a sol-gel process have been used as catalysts. The libraries were prepared with a pipetting robot, which automatically deposits the reaction solutions into the 207 wells of a slate library. After calcination the catalytic activity of the final products was tested in a microreactor. For that the catalytic properties of the library components have been detected by emissivity corrected JR-thermography. The best catalysts have been synthesised and tested under conventional conditions in a continuous flow reactor system.

P21 - Combinatorial Synthesis And Automated Characterisation Of Optical Gas Sensors
Athanasios Apostolidis1, Ingo Klimant2, Jane Lewis3, Darnian Andrzejewski', Otto S. Wolfbeis 1
1lnstitute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Regensburg, Germany
2lnstitute of Analytical Chemistry, University of Technology, Graz, Austria
3University of Wales, Swansea, Wales, United Kingdom
A scheme for the combinatorial synthesis and characterisation of optical gas sensors is presented. A computer controlled liquid handling station is applied for the synthesis of planar sensor spots. A major step of development consisted of the improvement of the durability of the set-up to organic solvents. The preparation of stock solutions of polymers, indicators and additives is performed manually. Thereafter, the preparation of mixtures of the stock solutions and the deposition of sensor material on a glass substrate is performed automatically by a dispenser controlled by the respective software.
This enables a wide variation of the components to result in combinatorial sensor material libraries. The glass substrates containing a library of 60 sensor spots are characterised in a computer controlled evaluation set-up. Its main components include:
1.) an xy-stage for positioning of a read-out unit to individual sensor spots
2.) an optical read-out unit consisting of a light source and an photodetector (in our set-up a spectrum analyser and a dual lock-in amplifier)
3.) a gas mixing device to realise an atmosphere of defined gas concentration.
A newly-developed software synchronises and controls each component of the evaluation set-up and the evaluation method. It includes the setting of the sample gas atmosphere by mass-flow controllers, the positioning of the detector unit connected to the spectrum analyser or the lock-in amplifier, the control of the characterisation devices and the data acquisition and storage. The performance of the system is demonstrated for the combinatorial synthesis of optical oxygen sensors and C02 sensors

P22 - Mg(II) Catalysed Asymmetric 1,3-Dipolar Cycloadditions On Solid Support
Fabio Rancati1, Giuseppe Faita1, Paolo Quadrelli', Alfredo Paio2, Pierfausto Seneci3 1University of Pavia, Pavia, Italy
2Glaxo SmithKline Group, Verona, Italy
3NAD, Munich, Germany
Evans' chiral auxiliary was grafted onto both Merrifield and Wang resins and, after functionalisation, they were used as chiral dipolarophiles in l,3-dipolar cycloadditions involving both nitnle oxide and nitrone. The cycloadditions were useful catalyzed by Mg(II). The increased regio, stereo and entantioselectivity were consistent with a reactive complex involving Mg(II) coordination to both the carbonyl oxygen atom of the dipolarophile.

P23 - Barium Magnesium Tantalate Thin Films Obtained By Sol-Gel: An Application Of HTE To High Frequency Dielectrics
Virginie Rouaux1, Frank Jermann1, Wilhelm F. Maier2, Olivier Guillou3
1Siemens AG, München, Germany
2University of the Saarland, Saarbrucken, Germany
3INSA, RENNES, France
High frequency ceramics allow a remarkable miniaturization of passive microwave components, used for example as resonators in mobile phones. Their development is commonly based on physical properties knowledge and time consuming optimizations. However, preparation and testing of a great number of ceramics need appreciable manpower and resources. In the last few years combinatorial methods, which are well established in drug discovery, have also been used in materials science, particularly in the search for new heterogeneous catalysts and new phosphors. The tendency is now to extend these methods to dense materials like dielectric ceramics.
The aim of the present work is the optimization of microwave ceramic thin films obtained by soft chemical processing. Barium Magnesium Tantalate samples (BMT) are prepared by sol-gel synthesis, where precursor solutions are deposited directly on a substrates by an automated liquid handler. Different parameters are tested like type and concentration of precursors, number of layers, thermal processing, surface quality and porosity of the films. These parameters influence the microwave properties of the thin films and their control should allow an extension of the method to high throughput synthesis of novel high frequency ceramics.

P24 - Sulfated Peptides As Heparin Mimics Designed For FGF Receptors
Socorro Vázquez Campos, Morten Meldal
Carlsberg Research Centre, Copenhagen, Denmark
Heparin, the most widely used natural anticoagulant, belongs to the family of glycosaminoglycan polysaccharides. It is composed of repeating 0- and N-sulfated disaccharide units. The biological activities of heparin are due to interactions with negatively charged proteins, and in particular fibroblast growth factors (FGF). Currently heparin is isolated from biological sources. It is a complex mixture of sulfated polysaccharides, which complicates quality control for the pharmaceutical industry. However, there are no practical synthetic routes available, since the chemical synthesis of carbohydrate-based heparin mimics is extremely difficult and expensive.
Therefore, sulfated peptides could be used to improve the accessibility and development of heparin mimics. Considering the negative charges and the sulfate groups of heparin are the key for its activity, the introduction of these charged groups on another scaffold, such as a peptide, might introduce activity. Two approaches will be used to generate sulfated peptide libraries: Direct sulfatation on solid phase and sulfated building blocks to use on solid phase peptide synthesis. Peptides obtained from the library were screened on bead for binding of the fluorescently labeled FGFs. Results from this study will be presented.

P25 - Intramolecular Cyclization Using Solid Phase Heck Reaction
Kenichi Akaji, Saburo Aimoto
Institute for Protein Research, Osaka University, Suita, Japan
A cyclic tetrapeptide derivative was synthesized on solid support by the Heck coupling of acrylic acid amide to a 3-iodobenzyl amine moiety. The cyclic derivative consists of a 3-substituted cinnamic acid template containing Arg-Gly-Asp (RGD), a tripeptide sequence known to bind to the glycoprotein Jib/lila (GP Jib/lila). GPIIbIIIIa is a membrane protein expressed on the surface of activated platelets which binds to fibrinogen to cause platelet aggregation.
Palladium(0)-mediated macrocyclization in a DMFIH2O/Et3N solvent system proceeded at 37°C within 4 h. The homogeneous product was obtained from the resin in ca 20 % overall yield (calculated from the starting resin). The cyclization efficiency on solid support was then compared with that in solution phase. The intramolecular cyclization in solution proceeded in proportion to the reaction time, but was relatively slow. In contrast, most of the precursor was converted to the product within 2 h. Thus, the Pd(0)-mediated intramolecular macrocyclization was found to be a unique reaction suitable for solid phase organic synthesis.
The solid phase Heck reaction can be applied to combinatorial library synthesis for designing high affinity ligands of GPIIb/IIJa. Cyclic RGD libraries which have diverse side chain structure combined with a variety of ring sizes were constructed by split and mix method

P26 - General Combinatorial Synthesis Of Tertiary Amines On Solid Support
Magnus Gustafsson, Roger Olsson, Carl-Magnus Andersson
Acadia Pharmaceuticals A/S. Glostrup, Denmark
A novel solid phase synthesis of tertiary amines involving iodide- or base-induced cleavage of the N-O bond of resin bound alkoxyammonium intermediates will be described. The quatemary intermediates were assembled via sequential reductive aminations followed by alkylation. Cleavage from the solid support afforded the target tertiary amines in good to excellent purity. Aspects of the scope and limitations as well as application of the method in the synthesis of a small focused library will be presented.

P27 - An Efficient And Convergent Route Towards Water-Soluble, Chiral And Amphiphilic Macrocyles
Tapes Bhattacharyya, Ulf J. Nilsson
Lund University, Lund, Sweden
A practical procedure for the synthesis of water-soluble, chiral and amphiphilic macrocyclic molecules is described. Acylation of p-xylylene diamine with Fmoc-protected amino acids, followed by removal of the Fmoc moiety afforded amino acid:p-xylylene conjugates as free diamines. These diamines were converted in a combinatorial fashion to symmetrical and unsymmetrical macrocycles via stepwise urea formation using p-nitrophenyl chloroformate. Complexation studies of these macrocycles with amino acids and carbohydrates in aqueous solution will be presented.

P28 - Novel Chiral Salicylic Aldehydes: Chiral Building Blocks For Combinatorial Synthesis
Albrecht Berkessel, Matthias Vennemann, Alexander H. Vetter
Department of Organic Chemistry, University of Cologne, Cologne, Germany
Schiff-bases are one of the most prominent ligand classes in asymmetric catalysis. For example, in 1995 Bolm and Bienewald reported a new and promising procedure for the asymmetric sulfoxidation of thioethers, using hydrogen peroxide as terminal oxidant: at a catalyst loading of as little as 1 %, the vanadium complex of a Schiff-base ligand derived from (S)-tert.-leucine and an achiral salicylic aldehyde effected the asymmetric sulfoxidation of thioanisole in high yields and with an enantiomeric excess of59%.
The diversity of combinatorial Schiff-base-libraries" can be broadened by the use of chiral salicylic aldehydes as building blocks. In addition to effects of structural differences, one can also expect matched- and mismatched cases for different combinations of chiral moieties.
Indeed, using a ligand derived from one of our chiral aldehydes, the efficiency of the asymmetric vanadium-catalyzed sulfoxidation of thioanisole could be increased to 70 % ee and 91 % chemical yield. The poster summarizes the synthesis of two pairs of enantiomers of two chiral salicylic aldehydes and the determination of their absolute configurations.

P29 - Synthesis Of A Novel Diamino-Anthracene Derivative And Its Conjugation With A Panel Of Amino Acids Building Blocks For Artificial Receptors
Sumita Bhattacharyya, Ulf 1. Nilsson
Lund University, Lund, Sweden
A synthetic procedure towards a diamino anthracene from 1,2,4,5-tetramethyl benzene 1, via benzylic bromination and Diels-Alder reaction with N-substituted maleimides followed by imide reduction, is described. The N-protected diamine 2 undergoes a second Diels-Alder reaction with DMAD followed by conjugation with different N-Boc protected amino acids, which provides a collection of chiral building blocks 3 for the synthesis of receptor libraries.

P30 - Solid-Phase Synthesis And Screening Of A Sulfahydantoin Library
Javier Garcial, Fernando Albericiol, Lois M. Bryman2, Ennque L. Michelotti2, Ernesto Nicolás1, Cohn M. Tice2
1Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
2Rohm & Haas Company, Spring House, USA
Combinatorial chemistry has an important role in life sciences for the discovery of new active compounds. In the agrochemical field, there is an interest in compounds having pKas in the range of carboxylic acids and logP values less than 3, as plant systemic crop protection, due to the fact that these compounds are transported from the leaves to the growing points of plants. In this regard, sulfahydantoin (1,2,5-thiadiazolidin-3-one 1,1-dioxide) derivatives lacking substitution at position 2 can be potential candidates for crop protection, due to the fact that proton at the 2-position has a pKa in the desired range.
In the present communication, a solid-phase synthesis of 2-unsubstituted sulfahydantoins will be presented. The five step synthetic strategy involves:
1.) incorporation of Fmoc-amino acids in a Wang type resin;
2.) removal of the Fmoc group;
3.) reductive amination with aromatic aldehydes;
4.) sulfamoylation of the secondary amine with sulfamoyl chloride; and
5.) cyclitive cleavage of the final product from the resin.
This procedure has allowed the production of a small but diverse library of the target compounds. Development of the chemistry, production, as well biological activity screening will be extensively discussed.


P31 - Design And Synthesis Of A Spiropiperidine Template Library
S. Cameron, Avril Robertson, S. Gussregen, D. MacManus, M. Allen
Tripos Receptor Research Ltd, Bude, Cornwall, United Kingdom
The spiropipendine moiety has been utilised by the pharmaceutical industry in the design of NK1 receptor antagonists. In addition, clinical results suggest that such antagonists may act as antidepressants. Therefore it was attractive to design a general screening library which incorporated this structural feature. The design and synthesis of such a library, with a substituted spiropiperidine as the core, will be presented. Criteria for the design and selection of the side-chain reagents will also be discussed.

P32 - A New Highly Efficient Strategy For Generation Of Indan Scaffolds Via A One-Pop Annulation Reaction
Anna Bengtson, Mats Larhed, Anders Hallberg
Uppsala University, Uppsala, Sweden
In lead identification processes there is an increasing need for new organic scaffolds of relatively small size. Efforts are devoted to the acceleration of compound production. Automated and focused microwave flash-heating has recently been proven to dramatically reduce reaction times in several different fields of organic chemistry.
Aryl triflates are useful starting materials in many types of palladium-catalysed reactions. We therefore decided to undertake a study of microwave-promoted high-speed triflatation of phenols. Complete conversion and high yields were achieved after only 6 minutes of irradiation
Palladium-catalysed reactions of the triflated salicylic aldehydes with ethylene glycol vinyl ether provided, in a one-step annulation reaction, a direct entry to protected indanones
In summary, we have developed a new rapid and robust method for the generation of aryl triflates and an efficient synthetic route from salicylic aldehydes to indan scaffolds. The annulation reaction is foreseen to permit selective functionalisations at both of the oxygen carrying carbons.

P33 - Synthesis Of Combinatorial Libraries Of PNA -Conjugates With Metal Complexes For Sequence-Specific Hydrolysis Of Oligonucleotides
Andriy Mokhir, Roland Kraemer
Ruprecht Karls University, Heidelberg, Germany
Synthetic restriction enzymes offer a series of advantages as compared with their natural counter parts. In particular, they have unlimited sequence specificity, normally better chemical stability, and lower cost of production. Potentially they can be useful in genetic engineering, anti-sense and anti-gene technology, either as drugs or regulators of gene expression.
We believe that conjugates of nucleic acids and their mimetics with molecules containing pre-oriented cationic fragments, such as metal complexes, polyamine, guanidine group, as well as nucleophilic inuidazolyl, hydroxyl, and thiol groups are the most promising leads in the search for new artificial restriction enzymes with improved binding characteristics, sequence selectivity and hydrolysis rates.
Herein we report on the synthesis of PNA-conjugates with metal complexes linked via spacers of different length and rigidity, which hydrolyse the phosphodiester backbone of target nucleic acids.

P34 - Solid Supported Synthetic Equivalents Of 3-Formylchromones And Chromones: Synthesis And Uses In Combinatorial Chemistry
Jose 1. Borrell1, Jordi Teixidó1, Elisabeth Schulerl , Enrique L. Michelotti 2
1Sarria Chemical Institute, Barcelona, Spain
2Rohm and Haas Company, Spring House, PA, USA
3-Formylchromone derivatives I have been extensively used as versatile solution phase building blocks for the synthesis of a large number of heterocyclic systems (Scheme 1). In contrast, despite their versatility in solution phase chemistry, resin bound chromone derivatives have received no attention. Several solution phase methods are reported in the literature for the preparation of substituted 3-formylchromones. The most convenient method to synthesize 1 uses substituted o-hydroxyacetophenones as starting materials which are treated using Vilsmeier-Haack reaction conditions (POCI3 in DMF) to afford the desired 3-formylchromones in good yields. As a part of our work in the area of combinatorial chemistry focused on the preparation of random libraries to be tested in agrochemistry, we decided to devise a strategy to obtain solid supported 3-formylchromones with a different degree of substitution on the phenyl ring. Now we wish to report that the treatment of bound o-hydroxyacetophenone 3 under Vilsmeier-Haack reaction conditions yields the diformyl derivative 4 or de monoformyl derivative 5 depending on the resin used as solid support. Thus, the treatment of 3 supported on the Merrifield resin (1% cross linked, 3.9 mmol/g) with POC13 in DMF at 50ªC achieves both a total conversion of 3 and the sole formation of the diformyl derivative 4, solid supported synthetic equivalent of the 3-formylchromone 1. In fact, when the resulting resin was cleaved with 1:1 TFAJDCM for 3 h at r.t., 3-formylchromone 1 was obtained in 25% yield. On the contrary, the use of the Wang chloro resin (1% cross linked, 1.13 mmollg) as linker afforded, after the cleavage step with 1:1 TFAIDCM for 1 h at r.t., chromone 6 as the major product even although large excesses of POC13 (2-20 equiv.) were used. In other words, the monoformylated intermediate 5 was selectively formed instead of the diformyl derivative 4. However, even in the optimal conditions found (10 equiv, of POC13, 50ºC, 3h) a mixture of 6 and 1 in a 94:6 ratio was obtained after the cleavage.
Consequently, we decided to obtain the monoformyl derivative 5 by using a different strategy. Thus, the treatment of 3 (supported on the Wang chloro resin) with ethyl formate (15 equiv.) and HNa (20 equiv.) in 1: 1 DMA/THE afforded 6 in high yield after cleavage with 1:1 TFA/DCM for 1 h at r.t. The use of the above methodology for the production of combinatorial libraries of heterocyclic compounds is fully described.

P35 - New High Speed Heck Coupling Reactions Assisted By Microwave Flash Heating
Karl S. A. Vallin1, Qisheng Zhang2, Dennis P. Curran2, Mats Larhed1, Anders Hallberg'
1Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden
2Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA
Today there is an ever-growing demand for new organic molecules of relatively small size for biological evaluation by high throughput screening (HTS) methods in the pursuit of new drugs. The combinatorial and medicinal chemist is therefore under constant pressure to increase the production of high quality compounds. In this reality, not only purification speed, but also reaction rate is of essence. Convenient methods to promote rapid reactions then become important. New automatic, focused microwave synthesizers constitute robust high-speed tools with the potential to help meet these demands and to become efficient superheating' devices in the medicinal and combinatorial laboratories.
This work demonstrates the use of microwave irradiation in internal Heck coupling reactions. This heating technique decreases the reaction times from days and hours to minutes without loss of regioselectivety and yield (eq 1). We herein report:
- A new highly regioselective palladium-catalyzed procedure for internal a-vinylation of electron-rich vinyl ethers and vinyl amides.
- A vinylation reaction with vinyl amides and vinyl ethers using new fluorous ligands for fast separation and recycling.
- An environmentally benign water/potassium carbonate additive as a thallium salt substitute in selective internal arylations of
vinyl ethers with aryl bromides [2b].

P36 - Solid-Phase Synthesis Of Carbamates, Carbonates And Ureas Using Spot Method
Katrin Michaelis, Norbert Zander, Ronald Frank
GBF Braunschweig, Braunschweig, Germany
A library of compounds for high-throughput-screening has been constructed using a collection of natural product fragments as building blocks. The key step of the synthesis was the formation of carbamates using a hydroxyl-functionalised natural product fragment, p-nitrophenylchloroformate as the activating agent and a support-bound amino group. The preactivation and formation of an intermediate carbonate from the alcohol and the p-nitrophenylchloroformate was carried out in solution. Without further work-up, the activated solution was reacted with amino groups bound to a polypropylene-membrane using the SPOT method . The developed chemistry enabels high throughput miniaturised synthesis of large compound libraries involving rare, precious building blocks.

P37 - Synthesis For N-Alkoxybenzimidazole Libraries
John M. Gardiner
Univeristy of Manchester (UMJST), Manchester, United Kingdom
Methodology for solid-supported synthesis of N-alkoxybenzimidazole libraries has been developed.

P38 - Combinatorial Solid-Phase Synthesis Of A 4(3H)-Quinazolone Library
Csaba Wéber, Attila Bielik, Gyorgy M. Keseru, Gyorgyi I. Szendrei, Istvdn Greiner
Gedeon Richter Ltd., Budapest, Hungary
Substituted 4(3H)-quinazolones has a wide range of biological activity, antibacterial-, antimicrobial-, cardiovascular-, anticonvulsant- and b-adrenoreceptor antagonist -activities has been reported. A traceless solid phase synthesis of 2,6 disubstituted-4(3H)-quinazolones on Wang resin has been developed. A 480-membered diverse sublibrary of a 1530 membered virtual library has been synthesized by combination of 30 cyclic secondary amines and 51 alcohols on Tecan Combitec Synthetizer.

P39 - Use Of Combinatorial Chemistry To Develop Photocurable Termoplastic Polyurethane Elastomers (Tpus)
Jaume Heras, José L. Falcó, Salvador Borrós, Jose I. Borrell, Santiago Nonell, Emma Polo Sarria Chemistry Institute, Barcelona, Spain
Polyurethanes are world wide used polymers in a great variety of forms. These polymers can be manufactured in an extremely wide of grades, in densities from 6 Kg/m3 to 1220 Kg/m3 and polymer stiffness from very flexible elastomers to rigid, hard plastic. Among the polyurethanes, elastomers are one of the most growing market materials. It is well known the chemistry related with type of materials. Almost all of these polyurethane elastomers are based upon segmented block copolymers having alternating soft and hard segments. Especially importance has the so-called spandex fibres. Chemically the soft segment is polyether or polyesther chains and the hard segments usually consist of substituted polyurethane and polyureas. More recently the use of photocurable dime diols as chain extenders has been proposed to improve the high temperature behaviour of the fiber. In this approach the conventional chain extender is partially substituted by a photocurable dim diol (i.e. 2,4 hexadiin-1-6-diol) and the fiber is photocured after spinning. The synthesis of polyurethanes has a big diversity due to these three variables: the diol (its hydroxyl index) and the chain extender (nature and ratios). For this reason, Combinatorial Chemistry can be a suitable technique to develop a library of photocurable thermoplastic polyurethanes. In this work the ratio Hard Segment / Soft segment, amount of photocurable chain extender and type of polyol have been chosen as diversity centers. The shore hardness, the yellowness and the compresino set of the polymers has been determined. The results show that the amound of photocurable chain extender can not be higher the 0,5%.

P40 - Solution-Phase Synthesis Of A Library Of Cyclic Tetraalkylammonium Derivatives
Angel Messeguer, Isabel Masip
Department of Biological Organic Chemistry, IIQAB, CSJC, Barcelona, Spain
Small organic molecules containing a quatemary ammonium moiety exhibit interesting activities towards different therapeutic targets (i.a., antibiotics, Leishmania, CNS). In the present communication, the design and synthesis of a new library of cyclic tetraalkylanunonium compounds is described. Three points of diversity derived from the nature of the amines selected and the cycle size as fourth diversity source constituted the main structural features of the library. The synthesis was carried out in a solution-phase multiple parallel strategy and solid-phase scavengers were employed for the removal of excess of reagents. In this context, the use of microwave irradiation facilitated these elimination steps.

P41 - Cyclic Pentapeptide Metal Ion Complexation: A Model Of The Binding Unit Of The Prion Protein
Maria C. Alcaro, Mario Chelli, Mario Ginanneschi, Anna M. Papini
University of Florence, Firenze, Italy
Prion diseases are fatal, neurodegenarative disorders in which the pathogenic event is the conversion of the monomeric membrane-anchored glycoprotein, the prion protein (PrPC) into the multimeric, protease-resistant scrapie isoform of PrP (PrPSc). The fundamental questions concerning the role of PrPC and the mechanism leading to PrPSc are unsolved. Recent evidences show that PrPC plays a role in copper metabolism in the central nervous system, and that the N-terminal region is the Cu2+ binding site. Moreover, it has been shown that the simple peptide unit HGGGW, present in the N-terminal region, possesses the necessary features to bind Cu2+. As a model to evaluate the induced structure of the PrP N-terminal region by the Cu2+ binding, we decided to synthesize the cyclic pentapeptide cyclo(-H-G-G-G-W-) and to estimate its complexation properties. We recently set up the synthesis of cyclodi-, tetra-, and hexapeptides by solid-phase synthesis and on resin head-to-tail cyclization, using the three-dimensional orthogonal strategy Fmoc/tBu/OAl on a trityl resin. In order to synthesize the cyclo(-His-Gly-Gly-Gly-Trp-), we prepared Fmoc-Xaa(Trt resin)-OAl (Xaa = His, Trp). We chose to synthesize the two building blocks to verify the dependence of the cyclization step on the amino acids involved in the ring-closure. The cyclopeptide prepared with the strategy previously described, was used to evaluate the Cu2+ binding properties by combined EPR, CD and NMR spectroscopic studies. Moreover, to verify the functional groups involved in the Cu2+ coordination we are interested to screen any position synthesizing with our strategy a library of cycle pentapeptides.

P42 - Parallel Solid Phase Synthesis Of Lipophilic Amino Acids
Maria C. Alcaro, Anna M. Papini, Mario Chelli
University of Florence, Firenze, Italy
The presence of a lipophilic moiety in a peptide sequence favors the absorption of the peptide onto the surface of the cell membrane, enhancing its biological activity. We previously reported that the simple introduction of a palmitoyl moiety at the N-terminus of the immunodominant epitope GpMBP(74-85) in Lewis rat was able to induce an increase in proliferation of long term T cell lines from Lewis rats immunized with the wild type peptide. For that reason we are interested in the synthesis of a series of lipopeptides, where a lipophilic amino acid is introduced at the N-terminus of the immunodominant epitope GpMBP(74-85). To this purpose we chose to synthesize a small library of g.d-unsaturated amino acids with an aliphatic
side-chain. Unsaturation could provide conformational information and increase the diffusion process of the peptide onto the phospholipid bilayer membrane. Starting from a-amino-g-bromo-butyric acid we synthesized its phosphonium salt in solution
and solid phase, in order to compare the two methodologies. Adequate protecting groups were used to further perform an Fmoc/tBu SPPS strategy. For the solid phase synthesis we anchored the a-amino-g-bromo-butyric acid to a Wang resin, protecting its amino function as Alloc, and then the phosphonium salt was prepared. This building block was used for the parallel synthesis of a small library of g,d-unsaturated amino acids, by Wittig reaction with different aliphatic aldehydes. The g,d-unsaturated amino acids after mild deprotection of the amino function, were used to synthesize a series of lipopepides of GpMBP(74-85) by Fmoc/tBu strategy.

P43 - Enamine Chemistry In Constructing Diverse Libraries For Screening
Kostyuk Aleksandr
Institute of Organic Chemistty, Kiev, Ukraine
Enamines are very well studied class of organic substances. A huge number of different elecrophiles react with enamines, thus permitting to modify the molecule and create libraries of compounds for screening. In many cases these substances are prone to hydrolysis and need additional work-up. We have found that enamines derived from cyclic ketones, namely cyclopentanones and ceclohexanones react easily with aromatic and heteroaromatic aldehydes giving 5-aryl(hetaryl)methylidene 1-morpholino-cyclopentenes and 6-aryl(hetaryl)methylidene- l-morpholinocyclohexenes. These new enamines are more stable in further reactions, especially for hydrolysis. At the same time they are sufficiently reactive and give a possibilityto synthesize diverse libraries using common industrially available reagents.

P44 - Combinatorial Library Of 2-Acylmethylbenzoazaheterocycles Transformations Products
Andrei Tolmachev1, Sergei Pipko 2
1lnstitute of Organic Chemistry, Kiev, Ukraine
2lnstitute of Organic Chemistry, National Academy of Science Ukraine, Kiev, Ukraine
We have found that benzimidazole, benzothiazole and quinoline compounds of type 1,2,3 are available, sufficient and effective syntones for obtaining of various potential biologically active heterocyclic products of type 4-8 and others. The simple synthesis procedures permitting free varying of substituents have been elaborated. Wide ranges of the above mentioned compounds have been obtained.

P45 - Combinatorial Chemistry With Natural Products As Templates
Alejandro G. Hernanl, Ralf Thiericke2, Susanne Grableyl
1Hans Knoll Institute for Natural Products Research, Jena, Germany
2CyBio Screening GmbH, Jena, Germany
Natural products are a structurally unique source of compounds for drug discovery purposes. Within our approaches towards combinatorial chemistry we focus on the use of secondary metabolites from microbial and plant origin and solid phase chemistry technology for the synthesis of compound libraries. Our goal is to generate small libraries with a maximum of structural diversity using natural compounds. We expect this approach to contribute substantially to lead structure finding and profiling of drug action mechanisms.
Miniaturisation and automation are economic and practical prerequisites for the combinatorial derivatization of valuable natural products. The synthesis of an analytical construct with good ionisation and UV-absorption properties allows the use of automated high-throughput techniques like LC-UV-MS or MALDI-TOF-MS and requests minimal quantities of the natural product template.

P46 - Combinatorial Derivatization Of Nortropin
Alejandro G. Hernan1, Ralf Thiericke2, Susanne Grabley I
1Hans Knoll Institute for Natural Products Research, Jena, Germany
2CyBio Screening GmbH, Jena, Germany
We have applied the concept described above to the modification of Nortropin. In our studies we were interested in the three dimensional orientation of the building blocks in a combinatorial library. The orientation is determined by the structural features of Nortropin and can be controlled through the application of regioselective reactions. Different orientation auxiliaries can also be used to enlarge the molecular space covered by the library members.

P47 - Exploring The Substituted Guanidine Moiety As A Pharmacophore Group
Miriam Royo1, Montserrat del Fresno1, Guillermo Gerona2, Rosario González-Muniz3, Antonio Ferrer-Montiel4, Fernando Albericio1, Carolina Garcfa-Martfnez4
1Department of Chemistry, University of Barcelona, Barcelona, Spain
2Department of Chemistry, University of Barcelona; Institute of Medical Chemistry, Madrid, Spain
3lnstitute of Medical Chemistry, Barcelona, Spain
4Center of Molecular and Cellular Chemistry, Miguel Hernández University, Elche, Alicante, Spain
Increasingly, guanidine compounds are considered to be promising molecules as lead structures for the design of new drugs. The guanidine function is present in many drugs such as cardiovascular, anti-histaminic, anti-influenza, anti-diabetic, and anti-bacterial agents. This moiety is fully protonated under physiological conditions due to its strongly basic character, a fact which is crucial for specific ligand-receptor interactions. Fully substituted guanidines are not so common but the presence could promote higher affinity between a particular ligand and its receptor. In our research program we have recently developed a convenient method for obtaining pentasubstituted guanidines on the solid phase.
We report here on the synthesis of different pentasubstituted guanidines libraries, for a wide range of biological applications, to explore this moiety as a potential pharmacophore group. Heterocyclic compounds such as diketopiperazines and hydantoins were chosen as scaffolds. These are common motifs in several products with therapeutic properies and have been used as templates for the rational design of several drugs by Combinatorial Chemistry. These scaffolds have been obtained by two new solid-phase approaches, in which a resin-bound linear dipeptide is cyclized before the final cleavage from the solid support. With this methodology we can introduce randomization and diversity in the spatial and positional arrangement of the functionalities around these cyclic templates, before releasing the compounds from the resin. These aspects, in addition to the biological activity of these libraries as neuroprotectors, analgesics, and multidrug resistance chemiosensitizers will be discussed.

P48 - Imidazoles Catalyze The Oxidation By Organic Peroxides
Ahmad Al-Ajlouni, Khaled Shawakfeh, Lina Al-Quaisi
Department of Applied Chemical Science, Jordan University of Science & Technology, Irbid, Jordan
Oxidation of indigo dyes, alkenes, organic sulfides by m-chloroberpoxybenzoic acid (MCPBA) has been enhanced significantly by the presence of iniidazole and 1 -alkylimidazole. Kinetic studies were carried out in semi-aqueous and organic solvents, such as MeOH and CH3CN. The reaction rate decreases with the ability of the solvent to form hydrogen-bonding with the MCPBA (CH3CN > CH3OH/CH3CN> CH3OH> CH3OHIH2O). The initial rates were first-order on the imidazole concentration even at relatively high ratio of imidazole/peroxide. The reaction profiles, due to the loss of the organic substrate with time, were straight in the beginning of the reaction and become exponential in the later stages. A mechanism that involves a rapid attack of the imidazole ring onto the peroxide followed by the reaction of peroxide-imidazole adduct (intermediate) with the organic substrate has been proposed. The final products of the oxidation of indigo blue and alkenes in CH3OHJH2O (8:2) were the corresponding 1,2-diols.

P49 - Combinatorial And Structure-Based Modifications Of The Vancomycin Antibiotic Core Structure
Christopher J. Arnusch, Roland J. Pieters
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
The vancomycin class of antibiotics represents an important group of natural antibiotics. Members of the group are clinically used as drugs of last resort against Gram-positive microbes resistant to conventional antibiotics. Their mode of action involves the peptide backbone of the antibiotic which forms a carboxylate binding pocket that binds to the developing cell wall of the bacteria thereby inhibiting its growth. This carboxylate binding pocket is important since vancomycin resistant enterococci (VRE) have developed resistance by substituting the terminal D-alanine residue for a D-lactate unit on the cell wall precursor. A modification therefore in the carboxylate binding pocket in a vancomycin-like molecule could possibly counteract this resistance. Combinatorial and structural based modifications of the vancomycin core structure will be done in an effort to improve binding to D-Ala-D-Ala ligand, but more importantly, D-Ala-D-Lac, found in the VRE. Cyclization of the macrocycle via nuclephilic aromatic substitution is performed on-bead which provides the basis for library formation. Using this methodology, variability is introduced in perhaps the most important area of the carboxylate binding pocket.

P50 - Towards A Synthetic Glycosidase With Combinatorial Chemistry
Jurgen Van Holen, Johan Van der Eycken
Laboratory for Organic and Bio-organic Synthesis, Ghent University, Gent, Belgium
Enzymes are capable of catalyzing chemical reactions in a very efficient and specific way. Glycosidases play an important role in vivo for trinmiing carbohydrate chains of glycoproteins. In industry, these enzymes are used extensively for the breakdown of polysaccharides like starch and cellulose. We wish to present here a solid phase combinatorial chemistry approach towards the development of an oligopeptide library with potential glycosidase activity.
The library is synthesized using the combine/split procedure [1] and counts 8.192 members each consisting of an oligopeptide chain with a b-turn. As glycosidases are known to stabilize the positive charge developing in the ITS during cleavage of the anomeric bond, the library is biased by incorporating aspartic and glutamic acid (AA3 and AA4). The b-turn should allow more interactions between the functional groups of the side chains. Active members are detected by screening against a test substrate [2], and their structures are identified by deconvolution.

P51 - Combinatorial Synthesis Of Diazo-Dyes: A Student Experiment
Ulrich Jordis, Matthias Treu, Manfred Hirnschall
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria
In an attempt to introduce the concepts of combinatorial chemistry and solid phase synthesis into the chemical curriculum we have developed the synthesis of known and novel diazo-dyes. The experiment is scalable both for the use of a synthesis robot as well as to manual synthesis and illustrates the concepts of the combinatorial technology. Furthermore, this poster will be designed to initiate a discussion for educational experiments for the proliferation of combinatorial chemistry.

P52 - A Simple And Economic Design For A Personal Synthesizer
Ulrich Jordis
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria
We have modified an existing design of a magnetically stirred parallel synthesizer that can be used both for sulution phase and solid phase chemistry and has advantages over existing designs using standard thread glassware. We will report about our experiences.

P53 - Adhesives and Polymers on the Fast Track
Holger Wildt, Helmut Blum, Ilona Lange, W. -D Herberg
Henkel KgaA, Dusseldorf, Germany

P54 - Automated, High Throughput Parallel Synthesis: Multi-Step Solution Phase Chemistries On The Trident Automated Platform
Mike Davies
Argonaut Technologies, Muttenz, Switzerland
High throughput parallel organic synthesis is now common practice in discovery chemistry research. Argonauts modular system and reaction cassette technology is aimed at parallel synthesis of focused small molecule libraries. The Trident automated platform has been designed to perform high throughput organic synthesis using this modular reaction cassette under truly inert conditions and in a robust, reproducible manner. This enables one to generate high quality libraries of small molecules and to access chemistry not normally amenable to automation.
The Trident Sample Processing Station (SPS) enhances the upstream and downstream sample handling capabilities of the system. Enhanced software capabilities also give the Trident synthesizer powerful reaction development and optimization capabilities.
Application of this technology in the syntheses of chemical libraries will be presented. A number of product purification and isolation protocols using polymer-bound scavengers and the ?catch and release? technique will also be discussed.

P55 - Novel Heterocyclic Libraries
Tatiana A. Smirnova, E. Svetrova, Alexander Bass, Pavel Kurapov, Eugene Babaev
Chemistry Department, Moscow State University, Moscow, Russia
Contribution from Combinatorial Chemistry Center (scientific and educational subdivision of Chemistry Department of Moscow State University).
We use liquid phase parallel synthesis to prepare heterocyclic libraries. 4 types of libraries have been synthesized, and for 2 types selected screening of biological activities has been performed.
The libraries involved:
1.) Previously unknown class of 5-amino/alkoxy indolizines (analogs and bioisosters of psilocine); several clenvatives selectively interact with beta-adrenoreceptors.
2.) Series of 1-amino-4-azolyl-1,3-dienes obtained by unusual ring transformation of 2-chloropyridinium salts. Compounds of this series display antimicrobial activity.
3.) Library of N,N'-substituted isonipecotic acid amides (ca.4000 samples) obtained by reductive amination reaction
4.) Library of previously unknown 1,5-disubstituted 2-aminoimidazoles. In contrast to other alpha-aminoheterocycles, alpha-aminoimidazoles belong to a "missing class" of heterocycles, and there is still no general synthetic pathway leading to this interesting family.

P56 - JKlustor- Software Tools For Clustering
Ferenc Csizmadia, András Volford
ChemAxon Ltd., Budapest, Hungary
To support clustering, a new software called JKlustor has been developed as an add-on module for ChemAxon's chemical database handling system, JChem. JKlustor can generate 2D hashed fingerprints for molecules, but real number descriptors may also be used during the calculation. The clustering process applies a version of the Jarvis-Patrick method, which is based on variable-length neighbor lists. In the case of fingerprint input, the measure of similarity is the Tanimoto coefficient. Another clustering module, applying Ward's minimum variance method and using Murtagh's reciprocal nearest neighbor (RNN) algorithm as a heuristic, is also planned to be introduced in the paper.
Since the system is written in Java, it runs under practically all operating systems. Both the input and the output can be either text files or database tables (practically all database engines having SQL interface are supported). The application will be presented by clustering an example molecule database.

P57 - A Library Of Indolylalkylamines As Building Blocks For Synthesis Of Pharmacologically Active Compounds
Eugene Zakurdaev, Elizabeth Balenkova, Andrew Gavryushin, Valentine Nenajdenko Chemistry Department, Moscow State University, Moscow, Russia
Recently derivatives of substituted 3-indolylalkylamines attract rapidly increasing attention because of the broad spectrum of their biological activity. A number of these substances has already found practical applications, especially as medicinal agents for the CNS disorders treatment. Being of pharmacological interest by themselves, substituted tryptamines, isotryptamines and their homologs also present extremely valuable "building blocks" for the variety of novel compounds aimed at drug design, medicinal, biological and adjacent studies.
Here we report the results of our synthesis of various 2 and 3-indolylalkylamines. A considerable bank of commercially unavailable arylhydrazines (about 100 entries) was previously created by our workgroup. Using some common intermediates obtained by the developed in our laboratory simple, inexpensive and large-scale procedure we have synthesised a variety of substituted tryptamines, isotryptamines and their homologs in multiscale (about 50-100 g of each) quantitiesAr\n-Substances, containing an unsubstituted, mono- or dialkylsubstituted amino group, as bearing a piperazine or homopiperazine moiety, are available according this scheme. We have also investigated the scope and limitations of this synthetic approach and worked out optimised protocols for different types of substituents. Continuous researches in the field of synthetic methods for practical elaboration of these compounds and their analogues are being performed in our scientific group.

P58 - Monitoring Of Solid Phase Reactions By Ft-Ir And Ft-Raman Spectroscopy
Orsolya Egyed
Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
During the past few years vibrational spectroscopy has become an increasingly important analytical tool for solid phase combinatorial chemistry, as it does not require additional chemistry to cleave the compound from the resin support prior to each analysis. In the present work our first results obtained in application of vibrational spectroscopy to the validation of multistep reaction sequence are presented. The method is based on monitoring the presence and/or disappearance of characteristic group frequencies. Important fundamental properties such as the distribution of the reactant on the solid support

P59 - Solution Phase Synthesis Of Pyrrolol2,3-Dipyrimidines
Svetlana V. Kluchko, Victor I. Gorbatenko, Vladimir N. Fetyukhin
I.E. LAB Ltd., Kiev, Ukraine
At present blocking tumor angiogenesis has turned out to be a very promising approach in anticancer therapy which has given an impetus to search for substances possessing this characteristic.
In this search of new promising tyrosine kinase inhibitors we have developed synthetic pro-cedures to obtain two combinatorial libraries of 4-amino-substituted pyrrolo[2,3-d]pyrimidines (4) and pyrazolo[3,4-d] pyrimidines (8) in liquid phase.

P60 - Synthesis And Evaluation Of A Split Mix Library Of Synthetic Receptor Molecules
Menno C. F. Monnee, Arwin 1. Brouwer, Rob M. J. Liskamp
Utrecht University, Utrecht, Netherlands
Presently, the fight against antibiotic-resistant bacteria has entered a crucial stage with the emergence of vancomycin resistant pathogens, e.g. vancomycin resistant Enterococci (VRE) and even more dangerous bacteria (Staphylococcus aureus) that are capable to evolve rapidly into multidrug-resistant strains. This threat will make the currently used antibiotics almost ineffective. Therefore the search for novel antibiotics is of utmost importance. One way to achieve this ultimate goal could be a combinatorial approach by which libraries of synthetic receptors will be synthesized and screened for binding of bacterial target molecules. To investigate this approach, a library of 6912 different synthetic receptor molecules was synthesized on the solid phase using the split mix technique with three subsequent reaction cycles using different amino acids. The fully deprotected library of synthetic receptor molecules was screened for binding with fluorescent ligands in phosphate buffer (pH 7.0). These serve as simplified model systems for the peptidoglycan cell wall precursors of Gram-positive bacteria. Active beads were selected by means of fluorescence microscopy, followed by "one bead Edman degradation' to identify amino acid sequences. The validation of these results is currently under investigation and will be presented on this poster.

P61 - New Heterocyclic Scaffolds Containing The 2.Fluoronitrophenyl Moiety
Alexandr Ivachtchenko, Alexandr Khizhan
Chemical Diversity Labs, Inc., San Diego, USA
4-Fluoro-3-nitrobenzoic acid containing the 2-nitrofluorophenyl moiety, which is susceptible to various chemical transformations, is a very popular scaffold for solid and solution phase synthesis of combinatorial libraries of substituted benzenes, N-hydroxyindoles, benzo[c]isoxazoles, benzazoles, 3,4-dihydro- l,4-benzothiazines, 1 ,2,3,4~tetrahydroquinolinC-2-& #lO86nes, ,5-benzodiazepin-2-oneS and 1,4-benzothiazepin-5-ones. These classes of compounds are characterized by a wide scope of biological activity, including anticancer, antibacterial, antiinflammatory, ataractic, antirheumatic, and other.
We were the first to synthesize new heterocyclic scaffolds containing the 2-fluoronitrophenyl moiety (1-6).
The scaffolds (1-3) were obtained by the interaction of the corresponding aminoacides with 4-fluoro-3-nitrophenylisocyanate and the subsequent cyclization of the forming ureas. The scaffolds (4-6) were obtained by the cyclization of the corresponding orthophenylendiamineS or 1 ~amino-2-mercapthoheterOcycle5 of 4-fluoro-3-nitrobenzoic acid.
Thanks to the presence of the 2-fluoronitrophenyl moiety these scaffolds present wide opportunities in solid and solution phase synthesis of combinatorial libraries of new bis-heterocycles with potentially high biological activity.
New scaffolds (1-6) and combinatorial libraries based on these scaffolds are commercially available from Chemical Diversity Labs, Inc.

P62 - Design Of Focussed Libraries Using "Bioanalogous' Transformation Rules Implemented To An Expert System (EMIL)
Akos Papp1, Toshio Fujita 2 , Ferenc Darvas 1
1 Comgenex, Inc., Budapest, Hungary
2 EMIL Systems, Kyoto, Japan
The common way of developing leads is to build combinatorial libraries around a promising core structures, make a diverse selection, if requested, then screen the library. The hits are subject of lead optimisation by classic QSAR techniques that target to find the best substituent combination without touching the structure of the scaffold. It is a limitation of the discovery process, because the most important part of the structure is decided when the whole procedure started, and there is no chance to change it later.
EMIL (Example-Mediated Innovation for Lead Evolution) provides a solution for the problem with alternating the skeletal structure of the hits by its implemented bioanalogous transformation rules. These rules are extracted from validated literature modifications resulting higher-ordered structures in the evolution of the leads.
The system is proved useful in ComGenex in the design of novel libraries with improved characteristics, and in providing pharmaceutically relevant alternative structures for analogue library synthesis.

P63 - ExclusiveDirect; A Novel e-CRM Tool
János Gerencsér, Gábor Pôcze, Akos Papp, Peter Arva, Adam Kotsis, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary
Remote management of organic syntheses of combinatorial libraries was a very slothful process, bearing many steps with the possibility of misconception, up to this day. The up-to-date follow up of a combinatorial synthesis process is a crucial issue, particulary among partners located on geographically distant places.
ExclusiveDirect gives a complex, easy-to-use solution for this problem. This e-CRM tool (Electronic Costumer Relationship Management) is a Web-based system, allowing the users (lab chemists, on-site and remote project supervisors, screening partners, contract project supervisors) to have an up-to-date information of particular projects in addition of having controlling information over the whole collaboration.
There are three different data access levels. On the first and lowest level individual reaction pathways, reaction protocols, yields and analytical data are accessible for on-site and remote users. On the intermediate level group survey of synthetic data and chemical properties can be monitored, while on the highest level timing, cost and actual status for the whole project can be overviewed.
ExclusiveDirect as a prototype of an organic chemical e-CRM system, presently manages over 100 projects, operated by 80 chemists in 11 laboratories under the control of supervisors in three different countries. The success in using this impressive system inspires us to make new and vigorous improvements this year to implement the more options, which could be useful in managing such a complex task.

P64 - HT Work-Up And Purification Technology Supported By Physicochemical Modelling
Agota Bucsai, Akos Papp, Gábor Pôcze, Lajos Godorházy, Ferenc Kálmán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary
Thousands of compounds has been prepared by ComGenex using parallel solution phase synthesis using automated liquid-liquid extraction work-up to achieve pure compounds. Application of this form of liquid-liquid extraction for the purification combinatorial library members involves a large number of difficulties if we want to apply the procedure routinely and simultaneously to 50-100 reaction products in small size within a wide structural variety.
At the end of the reactions the reaction mixture contains traces of starting material, reagents, auxiliary materials, and products from side reactions, which have to be removed. Crucial point is the appropriate selection of the solvents used during the extraction procedure, together with selection of the pH value of the aqueous buffer.
Physicochemical parameters (logD vs pH) of all the starting material, reagent and auxiliary materials are calculated with a ComGenex made software.
Considering this calculation results, conditions of liquid-liquid extraction can be optimised. Automated system can be used to achieve optimised conditions.

P65 - The Development Of A Web Based Client System For Outsourcing Drug-Like Molecules And Bioinformatic Data
Peter Arva, Adam Kotsis, Gábor Pöcze, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary
ComGenexDirect is an internet-based business-to-business shopping/outsourcing utility. It gives pharmaceutical and biotechnological companies as well as leading academic institutions the opportunity to search, view and acquire compounds from ComGenex's 'drug-like' small molecule library online. The system has been developed by ComGenex, Inc., one of the world's leading suppliers of novel, in-house synthesized compounds for drug discovery.
Intensive developments are on the way to extend the scope of ComGenexDirect with ADME-Tox (Absorption, Distribution, Metabolism, Excretion and Toxicity) related properties for the compounds. The increasingly diverse bioinformatic data is useful to researchers for evaluating and optimising new drug candidates at the earlier stage to increase the speed and efficiency of the discovery process.
For the future ComGenexDirect will increase the number of structures available to researchers, incorporate additional tools which can help clients identify those structures of relevance, and expand the range and types of bioinformatic and other information through provision of in house and third party data.

P66 - Site Distribution In Resin Beads As Determined By Confocal Raman Spectroscopy
Jurgen Kress, Abigail Rose, Jeremy G. Frey, William S. Brocklesby, Geoff W. Mellor, Mark Ladlow, Mark Bradley
University of Southampton, Southampton, United Kingdom
Scanning Confocal Raman spectroscopy was used to study the distribution of reactive sites within a resin bead used for solid phase synthesis. The distribution of NH2 groups in aminomethylated polystyrene resin (APS) was determined by doping with varying amounts of 4-cyanobenzoic acid. The extent of loading was determined by both elemental analysis and ninhydrin assays. The spatial distribution of the coupled 4-cyanobenzamide within the bead was determined to an in-plane resolution of 1 mm and depth resolution of ca. 4 mm, using the strong Raman CN stretching vibrational transition at 2230 cm-l. Dry and swollen beads were studied and the distribution was found to be essentially uniform throughout the bead in all cases.
Similar experiments were carried out with TG? resin. The samples with a loading lower than 100 % showed a pronounced higher number of functional groups in the outer region. However, the fully loaded beads showed a complete uniform distribution of functional groups all over the bead. This fact suggests that the reaction between the TG? resin and the 4-cyanobenzoic acid might be diffusion controlled under the reaction conditions.

P67 - Polymer-Bound HOBt: Use As Additivein Coupling Reactions And As Support For Protecting Group Transfer
Sophie Barthelemy, Paternuosto Marquis
Calbiochem-Novabiochem AG, Ldufelfingen, Switzerland
Solid-supported reagents have been shown to be extremely useful tools for simplifying work-up and reaction procedures in high throughput parallel solution synthesis.
The efficacy of various solid-supported HOBt resins, differing in the base resin employed, substitution and number of HOBt units attached per site, are compared in acyl transfer reactions in an attempt to determine the optimum configuration.
The use of HOBt resin as starting material for the synthesis of reagents for the introduction of protecting groups is also explored and the properties and applications of Z-OBt polystyrene resin are presented. The utility of these polymer-bound reagents is demonstrated in a multistep synthesis.

P68 - Novel Pyridinium Cationic Linkers For Solid Phase Synthesis
Sweta Ladwa
Loughborough University, Loughborough, United Kingdom
Introduction
A vital component in any solid phase synthesis is the linker group that tethers the compound being synthesised to the solid phase support. The earlier linkers were developed for peptide synthesis. Modifications have since been made to these types of linkers, which allows them to be used in the synthesis of non-peptides.
Aims
The aim of this research is to employ the use of N-alkyl and N-aryl pyridinium salts for the basis of a linker attached to a support. It is hoped to have the pyridinium cation acting as the linker, which could be eventually hydrolysed to reveal an amino group. Amino groups, whether they are heterocyclic or aromatic are known to posses a great deal of biological activity.
The inital aim is to try and attach a pyridine compound onto a suitable solid support.
Once this is successful, alkylation of the pyridine linker will be attempted using various comounds, an example being dodecyl bromide. If alkylation is sueessful, then cleavage of the amine compound will be attempted.

P69 - Marker Libraries: Facing The Challenge Of Chemical Genomics
György Dormán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary
In the age of high-throughput screening and combinatorial chemistry the drug discovery chain is still a lengthy, sequential approach. By the completion of the human gene-map understanding and healing a disease requires integration of genomics, proteomics and very recently metabolomics with early utilization of diverse small molecule libraries creating a more powerful 'total' drug discovery approach.
Future screening will be performed against the genome, proteome or metabolome indentifying functional target versus specific ligand pairs, metabolic and expression profiles in one highly integrated effort.
In the post-genomic era small molecules are used as chemical probes such as marker libraries for probing and profiling the genome, proteome and metabolome directly.
In our presentation we report specific photolabile marker libraries, that are able to form a chemically stable cross-link between the ligand and binding protein upon irradiation at specific wavelengths. The stable covalent linkage survives proteolysis, chemical fragmentation and sequencing, thus allows identification of gene-coded functional targets in a proteome and their specific hit compounds simultaneously.
In this new drug discovery approach called combinatorial chemical genomics or proteomics an optimal combination of marker and data-enriched discovery libraries provide a novel synergy for the drug discovery process at a very early stage.

P70 - Combinatorial Discovery Of New Thermal Rearrangement Pathways For Library-From-Library Approaches
Tamás Nagy, Tamás Karancsi, Gydrgy Dormán, Ferenc Darvas
ComGenex, Inc., Budapest, Hungary
Thermal rearrangements are widely studied in organic chemistry recognizing its mechanistic and synthetic importance. In order to estimate long-term stability of our combinatorial libraries a directed decomposition platform was developed treating 1000 cpds. under parallel stress condition 1. The platform is integrated with high-performance instrumentation (HPLCI ES APCI TOF mass spectrometry + NMR) and an algorithm calculates the Expiry Date.
This accelerated decomposition test system allows exploring new thermal transformation pathways. Selected library members have already been used for discovery and characterization of the thermally induced transformations by combining MS fragmentation with standard structural analytical methods. Using that methodology, an almost clean thermally induced chemical transformation was detected and elucidated on compounds containing 2-(?-antinoalkyl)-3H-quinazolin-4-one cores providing the same mass but different fragmentation pattern. To make the detection of the thermal rearrangement as a routine, search and identification of a specific MS fragmentation pattern (a rearrangement fingerprint) should be introduced by appropriate software.
In ComGenexs present combinatorial practice, a systematic search for the similar thermal behavior among the previously synthesized structurally related compounds is performed followed by the identification of such a rearrangement. This approach can be considered as an equivalent of the Houghten?s library-from-library approach to thermal rearrangements.

P71 - High Throughput Synchrotron X-Ray Micro-Characterization
Eric D. Isaacs
Bell Laboratories, Murray Hill, NJ, USA
Combinatorial synthesis has the potential for revolutionizing new materials discovery in a range of disciplines from biotechnology to materials science because of the efficient and systematic way in which it searches for new materials. Whether a combinatorial library of solid state films can yield useful electronic materials depends on the accurate and rapid characterization of up to thousands of ultra-low volume films. In particular, X-ray characterization is essential for identifying material phase and composition. Characterization of the ultra-low mass films that are the basic constituents of combinatorial libraries has required novel adaptations of X-ray microbeam techniques, such as mirrors to focus polychromatic X-ray beams to 0.5 ?m. In this talk we will describe several of these microbeam techniques and their applications to characterize combinatorial solid state systems including rare earth activated phosphors and high-Tc superconductors.
In collaboration with: 0. Aeppli, X.-D. Xiang, X.-D. Sun, P. Schultz, R. Haushalter, W. Yun, D. Manchini

P72 - An Improved Design Of A Parallel Synthesis Block
Ulrich Jordis
Institute of Organic Chemistry, Vienna University of Technology, Vienna, Austria
We have designed a low-budged parallel synthesis device using a simple aluminum heating block and modified reaction tubes with standard threads.
The poster will present details of the design and applications for parallel synthesis.

P73 - Combinatorial Libraries Of Benzimidazo[1,2-C]-6(5H)-Quinazolines
Alexandre Ivachtchenko, Sergey Kovalenko, Alexandre Drushlyak
Chemical Diversity Labs, Inc., San Diego, CA, USA
We established that the ring closure of 3-(2-aminophenyl)-quinazolin-4-on-2-thiones (1) takes place with elimination of oxygen, but not sulfur, and leads to benzimidazo[1,2-c]-6(5H)-quinazoline-3-thiones (2). The latter were transformed into S-substituted 3-mercapto- benzimidazo[1,2-c]-6(5H)-quinazolines (3).
Using the method of solution phase parallel synthesis we produced 'baby' combinatorial libraries CL0644 and CL0645 which include several tens of compounds each.
The purity and structure of synthesized compounds (2,3) are validated by NMR and LCMS methods.
'Baby' combinatorial libraries CL0644 and CL0645 containing from several tens to several hundreds compounds are commercially available from Chemical Diversity Labs, Inc.
1,2: Ri = H, COOH, COOCH3.
2: Ri, R2 = H, Alkyl, Aryl and other.
1-3: R2 = H, CH3, Cl and other.
3: R3 = CH2-Aryl, CH2C(O)-Aryl, CH2CN, and other.
'Baby' combinatorial libraries CL0644 and CL0645 containing from several tens to several hundreds compounds are commercially available from Chemical Diversity Labs, Inc.

P74 - Relationship Between Hydrophobicity and Antiproloferative Activity of Carboxamids Determined by Chromatographic Methods and MTT Assay
Ferenc Hollosy1, Janos Seprodi1, D. Eros2, L. Orfi2, Gyorgy Keri1 Miklos Idei1
1 Semmelweis University Budapest, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Hungary;
2 Institute of Pharmaceutical Chemistry, Budapest, Hungary
Hydrophobic properties of drug candidates play an important role ln the mechanism of their biological action. The knowledge of hydrophobicity of the molecules may help in drug design and in the clarification of the structure - activity relationship. One of the recent approaches is to estimate hydrophobicity of the drugs on the basis of physico-chemical data, including chromatographic parameters High pressure liquid chromatography (HPLC) and micellar electrokinetic chromatography (MEKC) provide excellent possibilities to perform these measurements.
The aim of the present study was to estimate hydrophobicity of carboxamids on the basis of experimentally determined retention data and on the basis of software calculated clogP data. Therefore, a series of carboxamids were synthesized on the basis of combinatorial chemistry, which resulted in two sub-libraries ("O" and "S' sub-libraries) and their hydrophobic properties were determined by HPLC as well as MEKC methods Furthermore, we have investigated the relationship between these data and the antitumor activity of the compounds. Biological effectiveness were evaluated by MTT-test on human epidermoid carcinoma cell line (A431) and
expressed as LD50 values. At the same time we have investigated the effects of exchange of oxygen atom for sulphur in the core molecule on the chromatographic and cytotoxic properties of carboxamids. We have also studied the influence of different substituents on these activities mentioned before
Our results showed that the 0-S exchange in the core resulted in relative large change in the retention parameters irrespective from the substituents. Alteration in the antiproliferative activity between the sub - libraries could be well explain according to their different hydrophobicities.

P75 - Synthesis of 3-Alkyl(Aryl)-5-(Alkylsulfanyl)[1,3]Thiazolo[4',5':4,5]Pyrimido-[1,6-/l]Benzimidazole-2(3/i)-Thiones
Alexandre Ivachtchenko, Sergey Kovalenko, Alexey Parkhomenko
Chemical Diversity Labs, Inc., San Diego, CA, USA,
Continuing construction of the new templates for combinatorial libraries containing pharmacophore fragments we implemented Gewald's method of condensation of 2-cyanomethylbenzimidazoles with isocyanates and sulfur. As a result of this reaction we obtained some new previously unknown scaffolds of polysubstituted 4- amino-5-(lH)-benzimidazole-2-yl)-3- ethyl-l,3-thiazole-2(3H)-thiones. The latter ones were transformed into l,3-thiazolo[4',5':4,5]pyrimido[l,6-a]benzimidazole-2,5(3H,4H)-dithiones by carbon bisulphide cyclization. Alkylation of l,3 thiazolo[4',5':4,5]pyrimido [l,6-a]benzimidazole-2,5(3H,4H)-dithiones
resulted in the corresponding l,3-thiazolo[4',5':4,5]pyrirnido[l,6-a]benzirnidazole-2(3H)-thiones.
The structures of final products and intermediates were validated by IR, NMR and mass spectroscopy methods. New scaffolds and combinatorial libraries based on these scaffolds are commercially available from Chemical Diversity Labs, Inc.

P76 - Combinatorial Libraries of Condensed Heterocycles Containing the 2-Mercapto-4 (3 H) -Pyrimidinone Fragment
Alexandre Ivachtchenko, Sergey Kovalenko, Alexey Ilin, Alexandr Drushlyak
Chemical Diversity Labs, Inc., San Diego, CA, USA;
We obtained new combinatorial libraries of condensed heterocycles containing the 2-mercapto-4 (3H)-pyrimidinone fragment. The obtained libraries are of indubitable interest for generation and optimization of biologically active leads since the heterocyclic compounds contained in these libraries are bioisostenc analogs of inhibitors of tyrosine kinases.

P77 - New Scaffolds Containing the Quinoline-6-Sulphonamide Moiety for Combinatorial Synthesys
Alexandre Ivachtchenko, Vladimir Kobak
Chemical Diversity Labs, Inc., San Diego, CA, USA
Proceeding from 3,3-dichloro-2-oxo-5-indolinesulphonydchloride we synthesized the new previously unknown izatines, 7H-quinoline-2-ones, quinoline - 4 carboxylic acids, quinoline-3,4-dicarboxylic acids and corresponding anhydrides which are of indisputable interest as scaffolds for solid- and solution- phase chemistry. The distinctive feature of these heterocycles is the presence of additional pharmacophore
sulphamide fragments. The first representatives of unique combinatorial libraries CL0646, CL0647 and CL0648 were obtained.

P78 - Antimicrobial proteins produced by microorganisms, a perspective for food preservation
Le Thanh Binh
Institute of Agricultural Genetics, Conhue, Tuliem, Hanoi, Vietnam
We have found several small proteins (sizes 3-8 kDa) produced by lactic acid bacteria showed very interesting antibacterial spectrum. They inhibited a range of lactic acid bacteria species, and especially to some pathogenic bacteria such as Staphylococcus, Bacillus subtilis, Salmonella typhimurium. In addition, it against the food
spoilage bacteria such as Clostridium. It seems to be a kind of bacteriocins. However, inhibition activities are different in comparison with the known bacteriocins. We have tried to use ammonium sulfate precipitation, and pH-dependent adsorption and desorption methods with the samples, however it expressed the same antibacterial
spectrum checked by the spot test method or agar difusion method.
It is interesting to continue further detailed research in order to confirm whether we found a new kind of bacteriocin, or a novel compound, or a mixture of several compounds etc. Moreover, it is biosynthesed by lactic acid bacteria which are considered as food grade bacteria and generally recognized as safe ( GRAS).