Searching Pfizer

The Pfizer group in the United Kingdom has been actively involved in the search for new Class III antiarrhythmic agents. It has patented a variety of structural types that make extensive use of the methylsulphonylamino moiety. These include indanes [173,174], pyridines [175,176], piperazines [177-179], benzazepines [180], bisarylalkylamines [181] and diazabicyclic compounds [182], From this extensive work, two compounds, UK-66914 (65) and UK-68798 (66), have entered clinical trials. Compound (65) increases the effective refractory period (ERP) of ferret papillary muscle by 25% at a concentration of 0.5 //M [183]. Whole-cell patch-clamp studies... 

The industrial production of penicillin by Pfizer in 1943 transformed the chemistry of natural products. Microbiology became its field and pharmaceutical research became its leading trend. The main driving force behind the research of the chemistry of natural products was and still remains to be human health care. Since the advent of antibiotics, many sources of natural chemicals, such as plants, fungi and bacteria, have been searched for antibacterials, anticancer products, immuno-suppressors and chemicals that affect the human psyche. This research was so successful that, even today, more than half of all pharmaceuticals are either natural products or derived from, or inspired by them. The market of antibiotics alone was ca. US 30 billion in 2005. The majority of antibiotics is produced by submerged fermentation of filamentous microorganisms such as soil prokaryotic actinomycetes and eukaryotic moulds, ascomycetes. 

ChemSelect AQB (Advanced Query Builder) A Pfizer in-house developed reusable Java component that allows users to query various molecular structure databases within Pfizer based on molecular structural information and/or other properties, retrieve, manage, and export retrieved hits. It has a functional role similar to MDL ISIS/BASE, but with many enhanced capabilities. PGVL Hub has embedded this reusable Java component within itself so that users can search for suitable reactants from various corporate reactants databases and inventory houses and return the hits seamlessly back into PGVL Hub design session. From user s point of view, the ChemSelect AQB component is just part of PGVL Hub. 

Pfizer s search for new treatments spans hundreds of research projects across multiple therapeutic areas—more than any other company. Our scientists, clinicians, technicians, and other professionals employ state-of-the-art tools ranging from robotic high-throughput screening (a method pioneered by Pfizer) to sophisticated genomic studies, to deliver a steady stream ofinnovative new products that enhance human and animal health. 

In 1998 chemistry suddenly appeared in the media in an exceptional way. Normally not a favourite of TV or the newspapers, chemistry produced a story with all the right ingredients—sex, romance, human ingenuity—and all because of a pyrazole. In the search for a heart drug, Pfizer uncovered a compound that allowed impotent men to have active sex lives. They called it Viagra. 

An extensive literature search, including Pfizer drug trial safety data, yielded no other reports of auditory hallucinations with voriconazole. Several other cases of musical hallucinations secondary to a variety of causes have been reported. They tend to occur secondary to temporal lobe insults and often have religious or patriotic themes. 

The great step forward was the development of submerged fermentation processes for antibiotics during the 1940 s, also pioneered by Pfizer. The search began for new classes of antibacterials with improved spectrum and potency for use in therapy, both for human and animal health use. 

The authors thank Dr. Beryl Dominy and Mr. John Hare of the Pfizer Technical Information Department for their help in computer-assisted searches of the scientific and patent literature and Mrs. Lynn Londregan, Mrs. Theresa D Amico, and Mrs. Linda Neilan for typing this manuscript. 

Most pharmaceuticals are based on heterocycles. An inspection of the stmctures of the top-selling brand-name dmgs in 2007 reveals that 8 of the top 10 and 71 of the top 100 dmgs contain heterocycles. This is not new. Heterocycles have dominated medicinal chemistry from the beginning. Consistent with their importance, many U.S. patents by pharmaceutical companies involve heterocyclic compounds. For example, a search of the patent literature from 1976 to September 2008 reveals that 1729 patents issued to Pfizer, as a representative company, contain the word pyridine. Merck has 3504 U.S. patents containing the word pyridine. This is not peculiar to pyridine as shown in Table 8.1 where other heterocycles were searched for three major companies. 

In 1998 chemistry suddenly appeared in the media in an exceptional way. Normally not a favourite of TV or the newspapers, chemistry produced a story with all the right ingredients— sex, romance, human ingenuity—and all because of a pyrazole. In the search for a heart drug, Pfizer uncovered a compound that allowed impotent men to have active sex lives. They called it Viagra. The molecule contains a sulfonamide and a benzene ring as well as the part that interests us most—a bicyclic aromatic heterocyclic system of a pyrazole fused to a pyrimidine. We shall discuss in detail how Pfizer made this part of the molecule and just sketch in the rest. The sulfonamide can be made from the sulfonic acid that can be added to the benzene ring by electrophilic aromatic sulfonation (Chapter 21). 

SOCRATES is used widely by Pfizer scientists in a VAX cluster computer environment at Sandwich and is well regarded both for its ease of use and its range of integrated search capabilities, allowing combinations of a variety of chemical and biological search parameters. 

This structure browsing procedure has proved very popular with users at Pfizer, both as a simple alternative to substructure search, and as a means of identif5dng analogous structures (lateral thinking ). Examples of the sort of similar structures produced from browse searches are shown in Figures 1 and 2 (not ranked in order) other examples are given in reference 4. Some of these would clearly be retrieved by conventional substructure searches, while others would not. 

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