Structures Systems Pfizer

Although sertraline appears to differ structurally from the other SSRIs, it is a phenylaminotetralin, in which the diphenylpropylamine nucleus is constrained into a rigid bicyclic ring system (Fig. 21.13). In the early work with the discovery of SSRIs at Pfizer, tametraline was initially synthesized in 1978. Animal studies showed it to be a stimulant and to block NE and DA uptake, a use that Pfizer was not interested in pursuing. Subsequently, one or two chlorine atoms were introduced into tametraline to produce new molecules that were potent inhibitors of 5-HT reuptake in the brain. One of the dichloro compounds was to become known as sertraline. 

Upjohn, Pfizer, and Monsanto are examples of companies that have decided to continue to support their in-house developed chemical structure database management systems. 

It was also fortuitous for us that one of John Figueras colleagues, Craig Shelley, had written a graphical structure output program that he was prepared to let Pfizer have for use in SOCRATES. This program, also written in FORTRAN, was integrated into our system with only minor modification. 

Jakes et al. implemented these screens in a pharmacophoric pattern matching system that is in use at Pfizer Central Research, U.K. ° It allows distances to be specified as either exact or a range of distances and the atoms to be exact matches or any atom type. In the first stage of the search, the bit map of the file of structures is searched by comparison with the bit map of the query screens. Test searches of 10 published pharmacophoric patterns against a subset of the Cambridge Structural Database demonstrate the effectiveness and the efficiency of screen searching. Specifically, the screen search eliminated, on average, over 95% of the molecules in the daubase. 

Magnetic materials — a glossary. Pfizer Corporation, Easton (1985) Systems and specifications. Steel Structures Paint Council (1990) Encyclopedia of polymer science and engineering, 2nd edn. Wiley, New York... 

The concept of molecular similarity calculation within chemical information systems was pioneered at Sheffield University and first introduced into operational systems at Pfizer Central Research (UK) " and Lederle . It is now well-established within chemical information systems, both commercially available and developed in-house, as described in other papers in this volume. It is a powerful concept, which may be applied to both 2-D and 3-D structural representations, and to chemical reaction information, and used to support similarity searching and browsing, and file clustering and partitioning. 

The molecules in these data-sets were then characterised by the presence or absence of the screens that are used for substructure searching in SOCRATES, the Pfizer Central Research chemical and biological databank system . In the case of the 2-D structures, there were 1315 atom-centred, bond-centred and atom sequence fragment screens in the case of the 3-D structures, there were 1471 inter-atomic distance screens. ... 

Bawden, D. Devon, T.K. Faulkner, D.A. Fisher, J.D. Leach, J.M. Reeves, R.J. Woodward, F.E. Development of the Pfizer Integrated Research Data System SOCRATES . In Chemical Structures The International Language of Chemistry] Warr, W.A., Ed. Springer-Verlag Heidelberg, 1988, pp. 63-75. 

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