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Combinatorial chemistry/ parallel synthesis and hta system in drug discovery laboratories

Development of an analytical technology for the full characterisation of combinatorial chemistry libraries. This high throughput analysis (hta) system will relieve the current bottleneck affecting drug discovery laboratories.

Introduction: The recent development of parallel combinatorial chemistry represents a breakthrough in the field of drug discovery technologies. Using combinatorial chemistry allows the synthesis of an exponential number of compounds per unit of work and time. The wide variety of structures and compounds synthesised can be tested biologically. This brings with it the possibility of reducing the amount of time required for research in producing a new drug. Currently, the key point to be resolved in drug discovery laboratories, however, is the need for the complete characterisation of the chemical libraries obtained in parallel or combinatorial chemistry, which would become possible with the new High Throughput Analysis (HTA) system to be developed in this project. At the present time, only around 5-20% of the compounds in chemical libraries have been characterised, which represents a large gap in knowledge and currently acts as the bottleneck preventing more rapid development of combinatorial chemistry. Objectives: This project is intended to develop an advanced EUROPEAN technology for drug discovery laboratories in the biotechnology and pharmaceutical industries, which would lead to a clear advantage over the technology originating mostly from U.S.A. laboratories. With this in mind, two clear objectives have been proposed for this project: A.- The development of a new HTA (High Throughput Analysis) system for drug discovery laboratories, which has its effectiveness demonstrated as part of a parallel synthesis project, such as is the case here. B.- The development of large chemical libraries of potential new drugs and biological screening. The HTA system can then be tested and developed using these libraries. C.- The technology developed will be readily applicable to other HTA environments like clinical screening and therefore extra value is created. These objectives will lead to the development of a EUROPEAN technology that will be far more advanced than the technology currently used for the development of projects involving combinatorial chemistry and the discovery of new drugs. It will also possible to transfer this to many other pharmaceutical companies and laboratories. This project will be developed thanks to the collaboration of 2 European companies in GERMANY and SPAIN. Each technological partner will develop a specific area to gain highly advanced joint end results that will improve the competitiveness of European technology, both in terms of drug discovery laboratories and current European HTA systems. Technological Contribution of Each Partner: -IUCT Co-ordinator of the project. Will develop the chemical libraries through combinatorial synthesis, providing over 12,000 compounds per year from 2003 onwards, which will, in part, be tested for biological activity. IUCT will be in charge of starting up the HTA system, carrying out any adaptations required and coming up with possible solutions to the problems which may arise. Co-ordinating the actions to be carried out on the system with BRUKER in order to achieve the final goal of a system that allows the complete characterisation in an average of 3 minutes per compound. -BRUKER BIOSPIN GMBH Supplies the HTA equipment, developing interfaces for both the hardware and software in order to provide an HTA system which can be applied to drug discovery via combinatorial chemistry, developing the necessary systems and adaptations as the project progresses. The basic analytical technology to be used is a synchronised system of flow-injection Nuclear Magnetic Resonance (NMR) and LC-DAD/MS (Liquid Chromatographt-Diode Array Detection/Mass Spectrometry) that consists of the following parts: liquid chromatography, (High Performance Liquid Chromatography (HPLC) with UV detection, mass spectrometry (MS-MS, etc.), flow nuclear magnetic resonance and robotic systems for dispensing and sample collection. This technology already exists for the individual parts and belongs to BRUKER, but the HTA system provisioned requires the integration of the aforementioned elements with one clear objective: to develop a completely integrated system which meets the needs of combinatorial chemistry laboratories. Keywords: HTA system, drug discovery, combinatorial chemis.
Acronym: 
HTA-EU
Project ID: 
2 900
Start date: 
01-01-2002
Project Duration: 
53months
Project costs: 
3 630 000.00€
Technological Area: 
Analytical Chemistry
Market Area: 
Pharmaceuticals/fine chemicals

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