Biomedical subjects

Paul J Edwards

Publications and source records attributed to Paul J Edwards.

6 recordsLinked to original sources

PubMed2006

The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.

The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered.

Animals↗

PubMed2006

The impact of parallel chemistry in drug discovery.

With the application of parallel synthesis of single compounds to drug-discovery efforts, improvements in the efficiency of synthesis are possible. However, for improvements to occur in effective drug design - a critical requirement to increase productivity in the modern pharmaceutical industry - the implementation of in silico design hypotheses that incorporate comprehensive information on a target, including considerations of absorption, distribution, metabolism and excretion, is also necessary. Concomitantly, the use of automated methods of synthesis and purification is also required to improve drug design. Combining all of these elements allows the possibility to uncover unique insights into a biological target quickly and to therefore accelerate the rate of drug discovery.

Automation↗

PubMed2006

Expediting drug discovery: recent advances in fast medicinal chemistry--optimization of hits and leads.

This article reviews the literature from January 2004 to January 2006 relating to the use of parallel chemistry compound libraries in drug discovery. Examples of libraries that have yielded active compounds across a range of biological targets are presented, together with synthetic details where relevant. The background of the biological target, and any structure-activity relationship that can be discerned from members of a library series, are also commented upon. A brief discussion of new technological developments in library design and synthesis, and likely future directions for parallel chemistry in the context of drug discovery, is also presented.

Animals↗

PubMed2004

Synthesis of (+/-)-secosyrin 1 and a formal synthesis of (-)-secosyrin 1.

[reaction: see text] A short synthesis of (+/-)-secosyrin 1 is presented that starts from an electron-deficient furan; reductive alkylation under Birch conditions gives rapid access to the natural product skeleton. Two aspects of stereoselectivity are explored, the first being directed dihydroxylation of a homoallylic alcohol. Second, the facial selectivity obtained during reduction of a highly substituted cyclic ketone was examined. Finally, our synthesis was rendered enantioselective by the reduction of a furan bearing a chiral auxiliary.

Catalysis↗

PubMed2003

Purification strategies for combinatorial and parallel chemistry.

This review surveys the methods developed for the purification of intermediates and final compounds originating from parallel and combinatorial chemistry. Included will be reviews of polymer-assisted purification, liquid-phase combinatorial chemistry, fluorous synthesis, liquid-liquid and solid-phase extraction, reverse-phase HPLC and supercritical fluid chromatography. A critique of each method is given, highlighting the methodologies strengths and weaknesses.

Chemistry Techniques, Analytical↗

PubMed2002

Solid-phase compound library synthesis in drug design and development.

This article is a subjective review of the literature between December 2000 and January 2002 related to the solid-phase synthesis of compound libraries for drug discovery and development. Examples of libraries yielding active compounds across a range of biological targets are presented, together with synthetic details where this is deemed of sufficient note. Background to the biological target and any structure-activity relationship, which can be discerned within members of a library series, is also discussed. A brief overview of new developments in solid-phase technology that is likely to impact upon drug discovery is also included.

Animals↗