MSDRL

The polymer Gantrez ES-335 was a generous gift from GAF (NORDEN) AB (Johanneshov, Sweden). Timolol was a generous gift from INTERX Research Corp., MSDRL (Lawrence, KS, USA). We are grateful to Mrs Lea Pirskanen for her skilful technical assistance. 

In-house chemical information management systems began to emerge at some of the larger chemical and pharmaceutical firms. These included CONTRAST and SOCRATES at Pfizer, SYNLIB at SmithKline, COUSIN at Upjohn, MSDRL/CSIS at Merck, and CROSSBOW at ICI (27). The Chemical Abstracts database was made available online in 1967 (28). In 1980 this became CAS ONLINE. A compre-... 

Acknowledgments. The preparation of the radiolabeled materials by the Labeled Compound Synthesis Group of MSDRL, the dosing and handling of the cattle and swine and the tissue preparation by Animal Metabolism/Branchburg Farm and the generation and interpretation of the nmr and ms data by Drs. Byron Arison and Lawrence Colwell are all greatly appreciated. 

The system, still operating to this date, is based on the approach used at the Walter Reed Army Institute of Research in Washington, D.C. The system was extensively enhanced to meet the specific needs of the Merck Sharp and Dohme Research Laboratories (MSDRL) and the Chemical Data Department (CDD) which is responsible for processing chemical structure information at Merck and Co., Inc. 

The MSDRL and Corporate computer support groups were concerned with the ease of software installation, its operational efficiency on the mainframe, data security provisions, access to an established vendor technical support group, and the availability of vendor supported terminals and plotters. Since a major commitment had been made toward an MSDRL VAX environment, a vendor supported VAX version was a significant requirement. 

A number of commercial systems that were available at the time were evaluated. Several failed to meet all criteria, due to a lack of U.S. installations and/or U.S.-based system support groups. Those that failed were DARC/Questel, Telesystemes, Paris, France the NIH-EPA Chemical Information System CHEMPIX, developed by Moreaux of Roussel-Uclaf and marketed by Chemical Information Management Inc. and SYNLIB, marketed by Smith Kline Beckman. The Upjohn COUSIN system, developed by Dr J Howe, was not commercially available. Chemical Abstracts Service (CAS) private file support was considered too expensive. Security with the CAS file was also a concern of MSDRL since it could not be brought in-house. 

At this point only two alternatives remained MACCS from Molecular Design Limited (MDL) and enhancing CSIS. A comprehensive study by the Corporate computer support group concluded that 36 man-months were needed to complete the work begun in 1982, to enhance CSIS to an online interactive system. MSDRL management felt that a commercial system would be able to meet the scientists needs in much less time. Also there were only a few IBM compatible terminals in MSDRL, in contrast to the many VAX compatible terminals. Acquiring more IBM terminals presented an additional cost factor to enhancing CSIS. The decision was made to drop CSIS from further consideration. 

Much was known about MACCS from demonstrations and extensive discussions with the MDL technical staff. However, many questions remained. An agreement was negotiated with MDL to provide Merck and Co., Inc. with a VAX version of MACCS for a ninety-day evaluation period. Concurrent with these negotiations were discussions on the design of MACCS data format comparable to CSIS format and a methodology for converting the CSIS database. The CDD and MSDRL staffs also received training in theuse of MACCS. 

The MSDRL computer support group reported that the software performed well on the VAX, although it was not optimised for that hardware. They recommended that MDL supply a plotting metafile which would address the need for local and large scale production plotting. 

Lease negotiations were concluded and MACCS was installed on the MSDRL VAX in November, 1984. A few project files were generated from CSIS. These provided opportunities to refine the CSIS conversion programmes and develop quality control procedures. Four chemists were hired and trained for the quality control work, and the database conversion began in the second quarter of 1985. CSIS records were converted in blocks of 6,000 records each and in L-number order. The L-numbers from each batch that failed to generate a connection table were saved in a separate file. A CSIS structure print and the corresponding MACCS plot were manually compared by the quality control staff for each record that was converted. Approximately 30% of these required some correction to the structure diagram and/or the text data. 

While the conversion was being done, a training program for the MSDRL community was developed. Course material was outlined, 35 mm slides prepared and a reference... 

The recent installation of MACCS-II with the Customisation and DBMS Interface modules has provided the capability to interface chemical structures with ancillary data. After receiving training from Molecular Design Limited, the CDD staff and Corporate computer support staff developed screens and sequences to customise MACCS-II for the MSDRL environment, and to replace the current version of MACCS. An orientation program was prepared to acquaint the user community with the new facilities and commands. Technical assistance was given to convert, where necessary, the scientists project files. 

Future plans call for investigating new technologies that will further integrate not only diverse databases, but hardware and software as well. Ultimately, terminals and PC s will be replaced by multiapplication workstations that will then provide the MSDRL scientists with greater potential for retrieving and analysing their data. 

Merck Sharp Dohme Research Laboratories, Dept, of Scientific Information, and Corporate Management Information Systems, MSDRL Systems and Programming Dept., Merck Co., Inc., Rahway, N.J. 07065... 

Chylack Jr LT, ManteU G, Wolfe JK, Friend J, Rosner B. Lovastafin and the human lens results of a two year study. The MSDRL Study Group. 

Like other pharmaceutical laboratories, Merck harp and ohme Research laboratories Is amassing an enormous amount of proprietary biological and chemical data. Moreover, the scientific staff at MSDRL Is using these data In Increasingly sophisticated ways In their search for products to Improve human and animal health. 

This data base Is searched nightly In batch mode and Is updated on a weekly basis. The structure file Is capable of being linked with other MSDRL files by providing structural Identification for reports upon request throughout MSDRL. 

Figure 24 Illustrates the Interaction among the various flies of both biological and chemical data which Is now fairly routine at MSDRL.

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