Susan Mary Dansereau

Bone active bisphosphonate mechanistic studies: synthesis of a 2-pyrindinylmethylene bisphosphonic acid via a photolytic ring contraction

Recent research on the bone active bisphosphonate class of drugs has led to highly potent nitrogen-containing analogs. The involvement of specific cellular targets and therefore a critical bisphosphonate pharmacophore required in the mechanism of inhibition of bone resorption is suggested. To further test this concept, the successful design of a potent conformationally restricted analog, based on the structure-activity relationships deduced from this research, has been accomplished via the preparation of a 2-pyrindinylmethylene bisphosphonate NE-10501 (3). An interesting photolytic ring contraction was utilized as the key step in the synthesis of this novel bone active compound.

One Module to Many Submissions: Generating Global Marketing Authorization Applications

Procter & Gamble Pharmaceuticals is using Documentums Workspace application and Xeroxs Document Assembler (XDA) application to assemble, publish, and produce global marketing authorization applications (MAAs). A modular approach is used to define the components of MAAs, using one module across regional applications whenever possible. Standards exist for each module so that format and content expectations are met. Based on the table of contents needed for each MAA, modules are sorted into a virtual document created in Documentum Workspace. Publishing results in portable document format (PDF) files that are used for production of electronic submissions and paper volumes (printed via Xerox DocuTech printers); tables of contents specific to each regional submission; hyper-text links for cross-references and table of content entries in PDFs; and volume and page numbers for cross-references and table of content entries in paper volumes. MAAs were successfully assembled and published for two new drug products using these tools.