bluuebunny/crossref_metadata_2025 huggingface dataset:
From Solution-Phase Studies to Solid-Phase Synthesis: A New Indole Based Scaffold for Combinatorial Chemistry
Authors: Orain David , Koch Guido , Giger Rudolf
Published: June 2006

The core structure of a natural product was selected as scaffold for combinatorial library synthesis. The key step for the construction of the 3,9-diazabicyclo[3.3.1]non-6-ene core is a novel Dakin-West/Pictet-Spengler reaction sequence. Route selection for library synthesis was determined
by solution-phase experiments. The solid-phase synthesis was developed based on the synthesis worked out in solution. A number of resins and linkers were studied to obtain the best loading and cleavage conditions. Potential target scaffolds using tryptophan, histidine and phenylalanine as
building blocks were investigated. These efforts led to the development of a synthesis protocol for a tetracyclic scaffold incorporating tryptophan, useful for the preparation of a combinatorial library.
Automated Parallel Synthesis of N-Alkylated-?-Amino Methyl Esters in Gram Quantities
Authors: Chamoin Sylvie , Roth Hans-Jörg , Borek Carsten , Jary Aline , Maillot Hugues
Published: June 2006

N-alkylated-?-amino acids and methyl esters are a special class of building blocks used for the production of combinatorial libraries. They have two reactive groups for their incorporation into chemical scaffolds and they bear on their 3-atom backbone two residues which contribute
to the diversity of a library. The work contained herein describes the methodology to synthesize N-alkylated-?-amino acids and methyl esters in a parallel and automated fashion. The aim was the preparation of a series of these building blocks in gram quantities. Furthermore, the
reported method tolerates that the N-residues as well as the ?-C residues bear a wide range of pharmacologically relevant functional groups, including ones with acid-labile protecting groups. Following a reductive alkylation procedure, using NaBH4 as reducing reagent, 14 different
?-amino methyl esters have been combined with nine different aldehydes. The products were isolated in satisfying purities and moderate to good yields. For the demanding extraction procedure (volumes of 150 ml), a recently developed automated system has been successfully applied and is
reported here for the first time.
Vibrational Relaxation Dynamics of Polyatomic Molecules in Solution
Authors: Pigliucci Anatolio , Vauthey Eric
Published: June 2006

Ultrafast time-resolved fluorescence measurements have been carried out to investigate vibrational relaxation dynamics of perylene derivatives in solution. The early results obtained with cyanoperylene in acetonitrile are presented and discussed.
From the DNA Gyrase Inhibitor Cyclothialidine to a New Class of Antibacterial Agents
Authors: Goetschi Erwin , Ricklin Fabienne , Reindl Peter , Masciadri Raffaello , Luebbers Thomas , Link Helmut , Kostrewa Dirk , Hebeisen Paul , Gmuender Hans , Angehrn Peter , Theil Frank-Peter
Published: June 2006

Cyclothialidine (Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from S. filipinensis NR0484. In this account we describe the identification of potent antibacterials structurally derived from this virtually neat enzyme inhibitor.
Sterilizable pH Sensor: Example of a Successful Technology Transfer Sterilisierbarer pH – Sensor: Beispiel einer erfolgreichen Zusammenarbeit mit KMU
Authors: Züst Christian
Published: June 2006

There has been a long collaboration between the Chemistry Department of the University of Applied Science in Burgdorf and MetroGlas, manufacturer of chemical sensors. The development of a unique pressure-regulating system for pH sensors is described. The agreement between the pressure
measured inside the electrode and theorectical values derived from kinetic data is very good. The pressure system has been patented, and sensors with the new system are now marketed by AppliSens.
Oxygen Donor Stabilized Alkaline Earth Metal Iodides
Authors: Fromm Katharina M.
Published: June 2006

Alkaline earth metal iodides show ionic behavior in water, but their bonding situation is not that clear in less polar solvents. The alkaline earth metal iodide adducts, i.e. [MI2(thf)5](M = Sr and Ba), [CaI2(L)4] (L = thf, H2O),
[Ba(OH)I(H2O)4] and [CaI2(dme)(diglyme)] (dme = dimethoxy ethane; diglyme = diethylene glycol dimethyl ether) are presented in this context and their bonding situation is discussed.
Molecular Switches Containing Transition Metals
Authors: Adamo Vincent , Belser Peter
Published: June 2006

The synthesis and the characterization of a novel dithienylethene-based molecular switch bearing metal complexes are described.
Linked Curriculum – Chemistry: Different from a Virtual University Vernetztes Studium – Chemie: anders als eine virtuelle Universität
Authors: Zürn Astrid , Paasch Silvia , Thiele Steffen , Salzer Reiner
Published: June 2006

Since 1999 the German Federal Ministry of Education and Research has been supporting the lead project 'Vernetztes Studium – Chemie' ('Network for Education – Chemistry'). Sixteen professors and their co-workers from Germany, Switzerland, and the United Kingdom are involved.
During a period of five years a novel internet-based modular system will be developed connecting theory and practice of the chemistry basic studies. This new approach will provide the basic chemical knowledge via the use of multimedia methods in the form of browser-based learning modules
which are compiled within an integrated educational concept. The students are able to choose different learning levels depending on their knowledge. Potential users are students and lecturers of chemistry and of other branches of study as well as laboratory assistants, pupils and interested
people undertaking further studies in chemistry.
Focal Point: Medicinal Chemistry: A. Ligand-Receptor Interactions: From Understanding to Design
Authors: Folkers Gerd , Kansy Manfred
Published: June 2006

The ultimate step in drug action is its interaction with the biological target. This process governed by physicochemical forces, should be as specific as possible. High specificity paired by high affinity is one of the main pillars of a safe drug. In a rational approach the close integration
of biophysical analytics, molecular biology and functional genomics and computational chemistry leads to a deep understanding of ligand–protein interaction at the molecular level. Switching forth and back between the virtual and real world, modern design processes allow for the creation
of sophisticated ligands for the benefits of future therapeutic intervention. This situation was reflected in the talks of four speakers of the morning session at the symposium having the focus on medicinal chemistry.In his compelling style Hugo Kubinyi gave a comprehensive overview
on ligand–receptor interactions. Besides teaching the basics, numerous examples coming from his rich and life-long experience in drug design pointed out both scope and limitations of the actual approaches in drug design.Osman Güner from Accelrys was not able to come but was
substituted by the European representative Remy Hofmann, who has longstanding experience in computational chemistry, especially focusing in the 3D-QSAR and pharmacophore description. His talk summarized the current approaches and provided insight in future developments which could soon
facilitate categorization processes based on pharmacophoric properties for huge compound databases.In the third talk, Leonardo Scapozza from the Institute of Pharmacy of the ETHZ delivered a fascinating and exciting research case from his lab. Based on the highly integrated technology
mentioned above he designs therapeutic genes for application in cell-based therapy. By use of these 'genetic switches' one might be able in future to control graft-versus-host reactions after tissue transplants. Not only the protein, designed to avoid immune recognition and delivered
via stem-cells, but also the adequate ligand has been designed to specifically interact on demand.The end of the session was marked by Wolfgang Jahnke, showing us the exciting new applications of nuclear magnetic resonance methodology. Especially for detailed studies in the
life sciences – recently acknowledged by the Nobel price granted to Kurt Wüthrich – NMR seems to develop as the ultimate technology.
Focal Point: Analytical Chemistry: Organic Trace Analysis – Challenges – Unsolved Problems
Authors: Oehme M.
Published: June 2006

The session 'Organic Trace Analysis – Challenges – Unsolved Problems' tried to give a 'state-of-the-art' view of some of the fundamental problems in organic trace analysis:• How to resolve very complex mixtures into single compounds and to deal with the resulting
flood of information.• How to improve resolution of a demanding separation and to speed up analysis time.• How to extract efficiently volatile polar compounds from water; a hardly solvable problem.In the following, leading experts in these fields give a synopsis progress
report and outlook about some pieces of the complex puzzle of possible solutions, namely the role and status of separation columns in high performance liquid chromatography, the possibilities and limitations of electrochromatography, the on-line combination of sample preconcentration/clean-up
with separation techniques, the modular on-line coupling of two GC columns and the enrichment of polar compounds in water by a LiCl-precolumn and high-resolution gas chromatography.
Focal Point: Hyphenated Mass Spectrometry: A. Liquid Chromatography – Mass Spectrometry
Authors: Giger W.
Published: June 2006

The identification of unknown compounds is essential in a wide variety of research areas and especially so in environmental analysis. Combining liquid chromatography with tandem mass spectrometry today allows the identification of substances that were not amenable to classical techniques.
Environmental toxicologists and chemists increasingly focus on chemicals that can potentially cause adverse effects in organisms and humans. Since effect concentrations are often very low, but also because the matrix can affect the sensitivity, selective enrichment has become a popular tool
for sample clean-up and lowering the limit of detection. Advances in environmental analysis, including techniques based on molecular recognition for selective enrichment or effect-oriented research were presented in this session.
Focal Point: Analytical Technology: Quality Assurance of Analytical Data: Measurement Uncertainty and Traceability in View of ISO 17025
Authors: Schreiber B. , Radvila Peter
Published: June 2006

Definition, determination and consequences of analytical measurement uncertainty were discussed. After a thorough explanation of actual procedures to handle uncertainty, the focus was switched to practical applications in process control, the meaning of qualitative analysis near the
limit of detection, a case study involving doping in sports events and the problems involved in setting legal limits (e.g. ILAC rules). Five experts from academia, industry, and governmental organizations as well as from R&D-driven companies gave their interpretation from different
points of view.
Focal Point: Inorganic Chemistry: Aqueous Organometallic Chemistry: From Life Sciences to Catalysis
Authors: Alberto R.
Published: June 2006

The Minisymposium in Inorganic Chemistry was held with international speakers from six different countries. It was dedicated to the rapidly growing field of aqueous organometallic chemistry. Since the research community is still relatively small, it was possible to cover with the contributions
the most relevant aspects of this new field. The widespread opinion that organometallics are generally unstable under aqueous and aerobic conditions could be relativated. The incentive of using water as a solvent in fundamental and applied research points towards very inspiring ideas.
An Afternoon Session for the High School Classes of the Regio Basiliensis – an Event with Tradition – on the Occasion of the International Trade Fairs 'r+d in life sciences' and 'REACH for process solutions', on 15 October 2002, in Basel Der Gymnasiasten-Nachmittag
ein Anlass mit Tradition, organisiert am 15. Oktober 2002 anlässlich der Messen 'r+d in life sciences' und 'Reach for process solutions' in Basel
Authors: Neier Reinhard
Published: June 2006

The Swiss Chemical Society together with the Foundation 'Schweizer Jugend forscht (SJf)' organised an afternoon session for the high school classes of the Regio Basiliensis. The Swiss Academy of Technical Sciences and the five big chemical companies Clariant, Ciba SC, Novartis, Roche,
and Syngenta helped to finance this event. Professors Süss-Fink and Pfaltz presented two talks under the title 'Catalysis, a well-known phenomenon, but with a modern touch'. Between the two scientific talks, Mrs. Noel Gmür Brianza presented the activities and aims of the SJf Foundation
with the help of an attractive video.
The First Careers Fair Specifically for Chemists in Switzerland
Authors: Belser Thomas , Kaiser Stefan , Menges Frederik , Nanchen Steve , Neumann Eva , Smidt Sebastian P. , Stohler Remo F.
Published: June 2006

Here we report on the first careers fair for chemists in Switzerland, contactchemists.ch. This event was organized by the Swiss Young Chemists' Committee Basel under the auspices of the SCS. Twelve companies accepted our invitation to take part and present their activities
in both poster booths and oral presentations. This was complemented by a workshop that aided applicants in forming a suitable job-finding strategy. An informal exchange of information was possible and made contactchemists.ch a success not only for the participating companies
but also for the numerous visitors. Synopses of the oral company presentations are included in this report.
Polymers at Surfaces and Interfaces at ZHW
Authors: Hirayama Martina , Dotta Pascal , Bührer Heiner G.
Published: June 2006

The properties of solids and liquids are strongly influenced by surface phenomena. At the interface of two phases, properties like wetting, adhesion and friction are determined by the degree of interaction between the phases. Controlling this interaction by means of chemistry at interfaces
represents the major research topic of the Laboratory of Industrial Chemistry at ZHW.
Technology Transfer at the University of Basel
Authors: Dalle Carbonare Bruno H.
Published: June 2006

The University of Basel is Switzerland's oldest university. Since 1996 the University has enjoyed an 'autonomous status' and is governed by a 'University Council'. Thus, the five hundred years of old academic tradition demonstrated a pronounced willingness to change. With its seven
faculties, the University of Basel covers all academic fields; however, two areas will be focussed on: life sciences and culture. The Office of Technology Transfer (OTT) of the University of Basel was created in 1997. In addition to the University of Basel, in Northwestern Switzerland the
Universities of Applied Sciences Basel (FHBB), Aargau (FHA), and Solothurn (FHSO) as well as the University Hospitals of Basel (KBS) have also entirely or partially entrusted their technology transfer to the OTT of the University of Basel. Over the past years, the OTT extended its services
beyond the conventional activities of technology transfer involving transfer of intellectual property, transfer negotiations and follow-up, as well as active scouting for exploitable know-how and research results. The successful record of the OTT is attributable to a number of success factors:
greater participation by researchers in technology transfer, higher productivity as a result of the innovative public–private partnership (PPP) between a private company specialized in technology transfer and the University of Basel and favourable financial incentives for the inventors.
The rapidly growing number of transactions shows the strategic significance of technology transfer and its various aspects for all stakeholders.
The Ambivalence of the Local Practices of Patenting within the BioValley Network
Authors: Bureth Antoine , Lévy Rachel , Pénin Julien , Wolff Sandrine
Published: June 2006

The production of novelty is more and more rooted in collective processes of interactions based on moving, heterogeneous networks involving new biotech firms, public research centers and big pharma companies. Patenting strategies have been investigated in a survey conducted within the
BioValley network. While many firms do not consider patents as efficient in terms of protection, and often favor, for that purpose, secrecy, technological advance, trademark or complementary assets, the results imply that firms use patents as strategic tools devoted to different aims. One
is to exclude rivals and create income from innovations. Another aim is that patents are seen as coordination tools, involved in the processes of diffusion and collective creation of knowledge, favoring interactions and facilitating the identification of potential partners.
Effectiveness of Cluster Associations from the Perspective of Firms Case Study: BioValley Association
Authors: Birch Jane A.
Published: June 2006

Supporting biotechnology clusters including cluster associations has been a significant component of regional economic development initiatives. This case study will contribute towards alleviating the dearth of research on cluster associations by assessing the extent to which they are
perceived to be effective by firms and, providing useful guidance not only for associations themselves, but also for firms and policy makers. In the literature realising the benefits of positive externalities and overcoming the existence of market failure emerge as rationale behind intervention.
Comparing these with firms' perceptions in this study produces a mixed picture. Participating firms highlight that the primary focus should be the facilitation of networks with cross-border relationships most important. However, forging international collaboration among firms seems to be a
challenge for this particular association.
ChemCon – A Successful Start-Up Story
Authors: Schmidt Monika
Published: June 2006

ChemCon is a good example of the approximately 300 new companies founded in the BioValley over the past 15 years that are involved in the life sciences in one way or the other. ChemCon is engaged in contract research and custom synthesis of active pharmaceutical ingredients and intermediates.
The products are manufactured on small scale under GMP-conditions. Based in Freiburg employing 40 people, ChemCon recently expanded into the USA.
'Tri-Nationality' as Major Challenge to Cluster Development – Experiences from the BioValley Initiative
Authors: Fuhrer Bernhard
Published: June 2006

The paper analyzes the organizational transformation of the biotechnology cluster initiative in central Europe. In the tri-national context of the BioValley (France, Germany, Switzerland), cross-border collaboration is the key variable under scrutiny. Two distinct development stages
are identified: The initial 'tri-national' phase characterized by a centralized governance structure and the second, 'regional' stage characterized by decentralized governance structures. In summary, neither organizational setups have managed to tackle the tri-national heterogeneity in a way
that would fully unleash the potential of the region. Individual and territorial egoisms were at the heart of this shortcoming. The article therefore concludes by suggesting that whatever executive form (centralized or decentralized) the organization takes in the future, it must implement
projects that are selected by an economically and territorially independent jury.
Financing, Incubating, Coaching, and the Cluster Effect
Authors: Bühler Fritz R. , Suter Christian
Published: June 2006

More innovation financing, incubating and coaching would be helpful for European biotechnology. Venture capital is available for all stages of biotech company development, providing companies are innovative and of high quality. Several venture funds are active in the BioValley. To compensate
for the shortcomings of management experience, a low-cost portfolio of integrated services could be provided by seasoned managers but the system has to be created, managed, and paid for by the small companies. Such shortcomings facing young companies can be overcome by seed financing, incubating
and coaching, and providing a dynamic regional biotech/life sciences development organization leading to a cluster effect. This allows much better use of available assets including sparse financial means.
Angiogenesis and Lymphangiogenesis: New Molecular Targets for the Treatment of Cancer and Inflammation
Authors: Detmar Michael
Published: June 2006

In order to grow beyond minimal size, tumors need to induce the growth of new blood vessels (angiogenesis), and systemic blockade of angiogenesis has been recently approved for the treatment of select types of human cancers. We identified the natural angiogenesis inhibitors thrombospondin-1
(TSP-1) and TSP-2 as potent inhibitors of ultraviolet light-induced skin damage and of cancer formation and metastasis, leading to new molecular approaches for chemoprevention. We also established the new concept of active tumor lymphangiogenesis, and we identified tumor lymphangiogenesis
as a novel prognostic indicator for metastasis and patient survival of human cancers. We discovered VEGF as a major pathogenetic factor in chronic inflammation and established anti-angiogenic therapy as a novel strategy to treat inflammatory diseases. The overall goals of our ongoing research
are to identify and to characterize molecular targets controlling inflammatory and tumor angiogenesis and lymphangiogenesis, using genetic disease models together with genomics approaches and chemical library screens, and to characterize genetic polymorphisms to determine disease susceptibility
and to develop individualized therapeutic strategies.
Pharmaceutical Chemistry at the ETH Zürich
Authors: Folkers Gerd
Published: June 2006

Pharmaceutical Chemistry at the ETH Zürich is devoted to research on structure–activity relationships. The combination of biophysical methods, like protein crystallography, mass spectrometry and NMR, with theoretical approaches such as QSAR studies and molecular mechanical
as well as quantum mechanical molecular modeling yield insight into ligand–protein recognition and has enabled a more fundamental understanding of ligand binding and transformation in several classes of proteins. The main biological targets are and have been, kinases, major histocompatibility
proteins, peptide hormones and most recently glycoproteins. In parallel the results fostered the improvement and new development of appropriate software tools for molecular design studies, the most recent of which is the automated integration of tautomeric states in docking.
Pharmaceutical Analytics at the Institute of Pharmaceutical Sciences
Authors: Altorfer Hansruedi
Published: June 2006

Some of our research activities in Pharmaceutical Analysis, Irradiation of Pharmaceutical Drug Substances, Development of Monographs and new Methods on Pharmaceutical Substances for the European- and Swiss Pharmacopoeia are described.
Pharmaceutical Biochemistry at the ETH Zürich
Authors: Scapozza Leonardo
Published: June 2006

Pharmaceutical biochemistry at the ETH Zürich is devoted to research on ligand–macromolecule interactions, combining experiments with computational data as closely as possible because we believe that there is no rational disease treatment without molecular understanding of
events. For this purpose biochemical/biophysical studies of target proteins in complex with their ligands are an essential part of the research. Complementary and integrated to it, a second field of research is dedicated to computational methods that play an important role in drug discovery
and development. These methods are strongly interconnected with the experiments and are used to generate new hypotheses to be tested experimentally. This approach has been made feasible by the progress of molecular biology and computer technology and is now extensively used in all major pharmaceutical
industries and thus has to be taught to students. Because of the interdisciplinarity of the research a multidisciplinary environment has been established. The scientific effort of the group is focused on cancer and antiviral research. Key targets of the research are kinases, namely thymidine
kinases and tyrosine kinases of oncogenic fusion proteins. In parallel and in view of the increasing amount of experimental data generated by the different -omics initiatives the group has started the development of appropriate software tools for data mining.
Tumor Targeting
Authors: Neri Dario
Published: June 2006

Cancer chemotherapy relies on the expectation that anti-cancer drugs will preferentially kill rapidly dividing tumor cells, rather than normal cells. Since a large portion of the tumor cells has to be killed in order to obtain and maintain a complete remission, large doses of drugs
are typically used, with significant toxicity towards proliferating non-malignant cells. Our research focuses on the targeted delivery of therapeutic agents to the tumor environment by means of specific ligands (antibodies or small organic binding molecules) to tumor-associated antigens. In
most cases, we target accessible antigens (such as the EDB domain of fibronectin or the C domain of tenascin-C) which are abundantly expressed around tumor blood vessels, but virtually undetectable in normal tissues.
Brain Disorders and Novel Therapeutics
Authors: Möhler Hanns
Published: June 2006

Using the power of genetic intervention, a strategy is illustrated which permits new insights into the pathobiology of brain diseases and the discovery of new therapeutic strategies. Brain function is based on a delicate balance between excitory and inhibitory neurotransmission. Selective
circuits of GABAergic inhibitory transmission were targeted by introducing point mutations in defined GABAA receptor subtype genes in mice (knock-in strategy). New behavioural phenotypes were generated which reflect various brain disorders. In addition, novel drug targets were identified
for the treatment of anxiety disorders, sleep disturbances, memory deficits, and schizophrenia.
SpeedScreen, a Label-Free, Affinity-Based High-Throughput Screening Technology for the Discovery of Orphan Protein Ligands
Authors: Filipuzzi Ireos
Published: June 2006

A high-throughput screening method, tailored to the discovery of ligands for both known and orphan proteins, was developed and implemented into Novartis' lead discovery process. Neither labeling of target proteins nor labeling of screening compounds is required, as the ligands are affinity-selected
by incubation of the protein with mixtures of compounds in aqueous binding buffer. Unbound small molecular weight compounds are removed from the target protein:ligand complex by rapid size-exclusion chromatography in 96-well plate format. The protein fraction is then analyzed subsequently
by liquid chromatography/mass spectrometry (LC/MS) for identification of the bound ligand(s). All sample handling steps and the analytics are rapid, robust, and largely automated, adopting this technology to the needs of present high-throughput screening (HTS) processes. This affinity-selection
technology, termed SpeedScreen, is currently an integral part of our lead discovery process. In addition to the screening of conventional compound libraries this technology can also be applied for the de-convolution of libraries originating from combinatorial chemistry efforts as well as complex
natural extracts.
Inhibitors of Plasmepsin II – Potential Antimalarial Agents
Authors: Boss Christoph , Brun Reto , Fischli Walter , Binkert Christoph , Meyer Solange , Prade Lars , Harris Luke , Coppex Lionel , Grisostomi Corinna , Corminboeuf Olivier , Bourgeois Jean-Marc , Furnari Rocco , Richard-Bildstein Sylvia , Weller Thomas
Published: June 2006

Malaria is a very serious infectious disease affecting over two billion people worldwide. Currently available antimalarial drugs are losing effectiveness due to the emergence and the spread of resistant parasite strains. In order to regain control over the disease, new treatments are
urgently needed. Drug discovery efforts in this direction are most likely to be successful if they target a novel mechanism of action. Such approaches will lead to antimalarial medicines that are functionally and structurally different from the existing drugs and therefore will have the potential
to overcome existing resistances. Our own efforts are focused on the aspartic protease plasmepsin II (PMII) which is a promising new drug target for future antimalarial therapies. We have found structurally simple, moderately active, non-peptide inhibitors of plasmepsin II which offer ample
opportunity for further optimization efforts.
Broad Spectrum Chemistry as Practised by Novartis Process Research
Authors: Mickel Stuart J. , Fischer Reto , Marterer Wolfgang
Published: June 2006

Three actual examples from the current product palette within Novartis Process Research will demonstrate the some of the variety and challenges encountered in modern chemical development.
Small Molecule Drug Discovery in the Fast-Changing World of Biotechnology
Authors: Halazy Serge , Schwarz Matthias K.
Published: June 2006

Generally referred to as Europe's largest Biotech company, Serono, with global headquarters in Geneva, has long been known for its portfolio of therapeutic proteins, which has, so far, resulted in market approvals of several recombinant products in the areas of reproductive health (Gonal-F,
Luveris, Ovidrel), metabolism-endocrinology (Saizen, Serostim), neurology (Rebif), and dermatology (Raptiva). In the late 90s, Serono's management made the strategic decision to add small molecule drug discovery to their research portfolio, with the aim of mimicking and further extending the
spectrum of action of the existing protein therapeutics with orally bioavailable next-generation products. As a hallmark of this new research paradigm, in late 1997, Serono acquired the GBRI (Glaxo Biomedical Research Institute), now SPRI (Serono Pharmaceutical Research Institute), located
just outside Geneva, and during the following year therein established a new, state-of-the-art Chemistry Department, with the necessary manpower, expertise, as well as the medicinal, analytical, and combinatorial chemistry equipment, including extensive structure- and ligand-based design capabilities.
In conjunction with a somewhat smaller Chemistry Department previously established at Serono's Boston-based research site SRBI (Serono Reproductive Biology Institute), Serono's chemists have now been working for around five years on a variety of small molecule drug discovery projects. As the
first small molecules emerging from these efforts have started entering human clinical trials, the present article will give an account on some of the work performed to date.
The Synthetic Development of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu®): A Challenge for Synthesis & Process Research
Authors: Abrecht Stefan , Harrington Peter , Iding Hans , Karpf Martin , Trussardi René , Wirz Beat , Zutter Ulrich
Published: June 2006

The evolution of the synthesis of oseltamivir phosphate (Tamiflu®), used for the oral treatment and prevention of influenza virus infections (viral flu) is described. Oseltamivir phosphate is the ethyl ester prodrug of the corresponding acid, a potent and selective inhibitor
of influenza neuraminidase. The discovery chemistry route and scalable routes used for kilo laboratory production as well as the technical access to oseltamivir phosphate from (–)-shikimic acid proceeding via a synthetically well-developed epoxide building block followed by azide
transformations are reviewed. Synthesis and process research investigations towards azide-free conversions of the key epoxide building block to oseltamivir phosphate are discussed. The search for new routes to oseltamivir phosphate independent of shikimic acid including Diels-Alder approaches
and transformations of aromatic rings employing a desymmetrization concept are presented in view of large-scale production requirements.
Molecular Informatics as an Enabling in silico Technology Platform for Drug Discovery
Authors: Jacoby Edgar , Schuffenhauer Ansgar , Popov Maxim , Azzaoui Kamal , Vangrevelinghe Eric , Priestle John , Ferrara Philippe , Faller Bernard , Acklin Pierre
Published: June 2006

The molecular informatics platform, as implemented today in the Molecular and Library Informatics (MLI) Technology Program at Novartis Institutes for BioMedical Research (NIBR) Discovery Technologies, will be presented. The mission of the MLI program is primarily defined to contribute
to the selection of screening hit and lead compounds using in silico methods. The MLI technology program aims to provide an integrated pipeline of computational methods for high-throughput in silico screening combining specific cheminformatics, bioinformatics, docking and 3D
pharmacophore applications. The four core activities of the group include: 1) Molecular diversity management; 2) In silico screening using HTD (high-throughput docking) and 3D pharmacophore searching; 3) Integrated analysis of HTS (high-throughput screening) and profiling data; and
4) Database management and software engineering in the field of in silico screening. The contribution of these activities to the drug discovery process will be summarized together with novel trends in the field.
The History of Explosives in Switzerland - Selected Highlights
Authors: Berger Beat
Published: June 2006

Around the time that Switzerland was established, the use of black powder or gun powder was also mentioned for the first time in this area. For the following five hundred years black powder was the only explosive known in Switzerland. The performance of black powder depended very much
on the production process. In the 19th century, Prof. Schönbein synthesized the new energetic material cellulose nitrate at the University of Basel. Also in the 19th century the use of fireworks in Switzerland was mentioned for the first time. During World War I a new cellulose nitrate
propellant plant was built in Wimmis. Today, new energetic materials which are not available commercially are synthesized and characterized in the laboratories of armasuisse.
Chemical Stability, Compatibility and Shelf Life of Explosives
Authors: Vogelsanger Beat
Published: June 2006

As with all highly energetic substances, explosives are not perfectly stable – their safety and functional features change during ageing. The extent of chemical instability strongly depends on the chemical structure of the explosive – aromatic and aliphatic nitro compounds,
secondary nitramines, and organic azides are relatively stable, whereas aliphatic nitrate esters suffer from much lower stability. The rate of ageing of an explosive can be strongly accelerated by incompatibility reactions between the explosive and contact materials. Stability and compatibility
of explosives can be investigated with numerous test methods. A classification of these test methods based on test design and type of investigated ageing phenomenon is suggested in this paper. Furthermore, the most important test methods are discussed regarding applicability, advantages, drawbacks,
and pitfalls.
Explosive Substances and Their Applications: An Overview
Authors: Bircher Hansruedi
Published: June 2006

A systematic overview about the different types of energetic material is given. The chemical composition, the reaction behavior, and the initiation mechanisms of explosives are discussed.
Effects of the Wire Length on H-Atom Transfer in 7-Hydroxyquinoline·(NH3)n: n = 2 and 3
Authors: Manca Carine , Tanner Christian , Leutwyler Samuel
Published: June 2006

Previously we have employed the 7-hydroxyquinoline·(NH3)n ammonia-wire clusters to study excited state H-atom transfer along a sequence of hydrogen bonds. H-atom transfer experimentally occurs for n = 4 excited to its vibrationless S1 state, for
n = 3 with additional excitation of ammonia-wire vibrations (~200cm–1). However, for the n = 2 cluster, no reaction is observed, even with additional excitation energy of 900cm–1. CIS calculations have been performed on the n = 2 and n = 3 clusters to understand
the effect of the wire length on the energy profile of the reaction. The enol ? keto reaction is always exoergic, and the barrier for H transfer to the proximal ammonia controls the reaction kinetics.
Modelling Properties of Molecules with open d- or f-Shells Using Density Functional Theory
Authors: Daul Claude A.
Published: June 2006

A new, non-empirical, Density Functional Theory (DFT) based Ligand Field (LF) model is proposed. The calculation involves two steps: (i) an Average Of Configuration (AOC), with equal occupation of the d- or f-orbitals is carried out, (ii) with these orbitals kept frozen, the energies
of all Single Determinants (SD) within the whole LF manifold is performed. These energies are then used to estimate all the Racah- and LF-parameters needed in a conventional LF calculation. The results of this first-principle prediction are in very good agreement with the experimental values.
Sample calculations of tetrahedral and octahedral Cr-complexes, hexa-acquo Ni(II)-and octaacquo Gd(III)-complexes are used to validate the new model and to analyse the calculated parameters.
Potential Energy Surfaces for Vibrational and Rotational Wave Packet Motion in Polyatomic Molecular Systems
Authors: Cuvelier Frédéric , Hervé Stephen , Marquardt Roberto , Sagui Kenneth
Published: June 2006

We develop analytical functional forms for the generation of full-dimensional representations of potential energy surfaces for polyatomic molecules of the type AX1..Xn, with one central atom A and peripheral atoms Xi, and for diatomic molecules adsorbed
on surfaces. Examples are shown for NH3 and CO(ads)/Cu(100). Such forms are useful for realistic derivations of potential energy surfaces with applications on the calculation of ro-vibrational spectra and time-dependent molecular quantum dynamics. As an example, the effects
of rotational motion and orientation on the vibrational wave packet dynamics of HF merged in an external electric field are discussed.
Ab initio Vibration-Rotation Spectroscopy
Authors: Thiel Walter
Published: June 2006

This review surveys recent theoretical work from our group in the area of vibration-rotation spectroscopy. It addresses the computation of anharmonic force fields and spectroscopic constants in the context of rovibrational perturbation theory as well as variational calculations of vibrational
levels, on the basis of highly accurate ab initio potential energy surfaces. Results are presented for three case studies involving difluorovinylidene, bismuthine, and ammonia, to illustrate current contributions from ab initio quantum chemistry to spectroscopic studies.
Quantum State Resolved Studies of Gas/Surface Reaction Dynamics
Authors: Beck Rainer D. , Rizzo Thomas R.
Published: June 2006

Laser light is an invaluable tool for detailed experimental studies of chemical reactions. The ability to prepare reagent molecules in specific quantum states and to resolve the quantum state distribution of reaction products using laser radiation has been key to the field of chemical
reaction dynamics, which studies chemistry at a fundamental microscopic level. Today, state-resolved experiments are common for unimolecular and bi-molecular reactions in the gas phase, but equivalent measurements for gas/surface reactions have only recently started to appear. This contribution
reviews the methodology developed in our group at the EPFL for the quantum state resolved investigation of molecule/surface reactions and gives representative results on the dissociative chemisorption of methane on single crystal nickel surfaces.
Celebrating Dieter Seebach's Contributions to Science: A Bitter Sweet Occasion?
Authors: Hook David F.
Published: June 2006

The 2004 Spring Meeting of the Swiss Chemical Society played host to a one-day symposium reflecting on Prof. Dieter Seebach's impact on modern day chemistry. A broad cross-section of science was discussed by the four speakers: Jean-Marie Lehn; Christopher T. Walsh; David A. Evans; and
Peter B. Dervan, mirroring in some small way the diversity of Dieter Seebach's own research during the past 40 years.
Tin-Free Radical Carboazidation
Authors: Panchaud Philippe , Renaud Philippe
Published: June 2006

The radical carboazidation of alkenes could be achieved in water using triethylborane as initiator. This efficient process is complete in one hour at room temperature in an open system. These new tin-free azidation and carboazidation conditions are environmentally friendly and enable
reactions to be run with an excess of either the alkene or the radical precursor. Furthermore, 3-pyridinesulfonyl azide could be used in order to avoid tedious purifications, especially when the reaction product has a similar chromatographic behavior to benzenesulfonyl azide, our original
azidation reagent.
Ni(II)-PPP Complexes: From the Hydroamination of Activated Olefins to the Synthesis of ?-Amino Acids
Authors: Fadini Luca , Togni Antonio
Published: June 2006

Complexes of the type [Ni(PPP)(solvent)]X2 containing ferrocenyl tridentate ligands have been prepared and used as catalysts in the asymmetric hydroamination of activated olefins (i.e. bearing an electron-withdrawing group). In the case of acrylonitrile derivatives
the addition of aliphatic amines displayed relatively high activities and moderate enantioselectivity (yields up to 99%, ee's up to 69%). The reactions were also carried out in various ionic liquids (imidazolium and picolinium salts) with results comparable to those obtained in common organic
solvents. Additionally, we describe the conversion of several products to ?-amino acid derivatives.
Chemo-Enzymatic Synthesis of Antagonists of the Myelin-associated Glycoprotein (MAG)
Authors: Gao Gan-Pan , Schwardt Oliver , Visekruna Tamara , Rabbani Said , Ernst Beat
Published: June 2006

Ganglioside GQ1b ? is the most potent antagonist of the Myelin-associated glycoprotein (MAG) identified so far. For the efficient synthesis of the partial structure of GQ1b ? and derivatives thereof, a chemo-enzymatic strategy using the ?(2?3)-sialyltransferase
ratST3Gal III (EC 2.4.99.6) was applied. Besides the natural substrates Gal? (1?3)GlcNAc (19) and Gal? (1?4)GlcNAc (20), the disaccharides Gal? (1?3)GalNTCA?-OSE (9), Gal? (1?3)GalNAc?-OSE
(11), and Gal? (1?3)Gal?-OSE (14) were also tolerated by the enzyme and were transformed to the target structures in preparative scale.
On-line Electrochemical Tagging of Free Cysteines in Peptides during Nanospray Ionisation Mass Spectrometry: An Overview
Authors: Dayon Loïc , Roussel Christophe , Girault Hubert H.
Published: June 2006

A recently developed nanospray interface for mass spectrometry (MS) was used to electro-generate benzoquinone from hydroquinone. When spraying biomolecules containing free cysteine residues in the presence of hydroquinone, the thiol cysteine moiety reacts via a 1,4-Michael addition
with benzoquinone electrochemically generated at the electrode. The on-line labelling of cysteine was optimised using several substituted hydroquinones, and the kinetics of the addition was investigated by electrochemical methods such as cyclic voltammetry (CV). The mass spectrometric analysis
of peptides containing up to three cysteines residues in the presence of selected probes allows the direct quantification of free cysteine residues. The on-line tagging method provides both the mass of the untagged peptides and that of the tagged peptides.
Fluorine-Substitution in Cholesteryl Ester Transfer Protein Inhibitors (CETPInhibitors) – Biology, Chemistry, SAR, and Properties
Authors: Paulsena Holger , Zaiss Siegfried , Schmidt Delf , Bischoff Hilmar , Bremm Klaus-Dieter , Naab Paul , Lögers Michael , Wirtz Stephan N. , Stoltefuss Jürgen , Schmidt Gunter , Brandes Arndt , Schmeck Carsten , Antons Stefan
Published: June 2006

The inhibition of the cholesteryl ester transfer protein (CETP) provides a method for the elevation of the high density lipoprotein cholesterol (HDL-C) level, i.e. the 'good' cholesterol. The expected anti-atherogenic effect
of this approach is independent of the proven benefits of lowering the low density lipoprotein cholesterol (LDL-C) level, i.e. the 'bad' cholesterol. A medicinal chemistry project is presented starting from the first screening hit to the second generation
development candidate. The structure–activity relationship, the syntheses and the role of fluorine during optimization, as well as the biological activities are discussed.
Synthesis of Some Arylsulfur Pentafluoride Pesticides and Their Relative Activities Compared to the Trifluoromethyl Analogues
Authors: Crowley Patrick J. , Mitchell Glynn , Salmon Roger , Worthington Paul A.
Published: June 2006

: Examples of pesticides containing an arylsulfur pentafluoride group were made and their biological activities compared to the corresponding trifluoromethyl analogues. A phenylsulfur pentafluoride analogue of the insecticide fipronil, screened against a resistant strain of Musca
domestica, showed higher activity than the corresponding trifluoromethyl analogue.
?-Fluoro-Benzylphosphonates as Reagents for the Preparation of 1-Fluoro-1-Aryl Alkenes and ?-Fluorostilbenes
Authors: Allmendinger Thomas , Fujimoto Roger , Gasparini Fabrizio , Schilling Walter , Satoh Yoshi
Published: June 2006

The preparation of several fluoro-benzylphosphonates Ar-CHF-PO(OEt)2 and their Wadsworth-Emmons type olefination with aldehydes and ketones are described affording fluorostyrenes and fluorostilbenes. Some of these compounds are incorporated into target molecules tested as
drug candidates.
Emergency Response Organisation for Toxic Gas Emissions
Authors: Zufferey Gérard
Published: June 2006

Toxic gas emissions are the most severe chemical incidents, since chemicals disperse quickly from the source to the site and residential areas. Risk is minimised by design measures, alarm systems, and emergency response planning. Site personnel and people living in the vicinity must
be informed and trained on the correct actions to take. The organization for possible incidents consists of a main command and control centre, a forward command centre and the fire brigade.
Inflammable Liquids – Hazards and Their Prevention
Authors: Ebener Otto
Published: June 2006

Spillages and fires with inflammable liquids are an enormous challenge for a task force. Only wellequipped and well-trained organisations are in a position to fulfil these tasks. This means firemen should be aware of the dangerous properties of inflammable liquids. The equipment and
training must be continually examined and, if necessary, adapted.
Pumped Transfer of Liquefied Gases
Authors: Ochsner Felix
Published: June 2006

The transfer of liquefied gases comprises a special hazard potential. Therefore special equipment and expertise is necessary. It is not possible for every HazMat base to hold its own equipment. Therefore in Switzerland the Flüssiggaspikett der Ostschweiz and DSM Nutritional Products,
Sisseln, can be called out to provide help if incidents with liquefied gases occur. A case study of a real mission is presented. Furthermore technical specifications of key items and the experience of the author are provided.
Fire-Fighting and Hazardous-Materials Response Units in the Gotthard Road-Tunnel
Authors: Cathomas Norbert , Bühlmann Benno , Mulle Anton , Christen Hermann , Husner August
Published: June 2006

In the Gotthard tunnel, the transport of hazardous material is limited in quantity. The total amount of hazardous material has nonetheless increased in the last few years. The technical and organizational measures taken to deal with this fact are outlined in the following article. Moreover,
problems related to a fire in a tunnel (those that are linked to an incident with chemical substances) will be addressed. Some of the most important findings arising from the fire of October 24, 2001 will be illustrated and some suggestions on how the fire brigade and the hazardous-materials
response teams act in such cases will be presented.