William J. Hoekstra

Recent advances in peroxisome proliferator-activated receptor science.

The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors, a set of three receptor sub-types encoded by distinct genes, function as lipid sensors to regulate a broad range of genes in many metabolically active tissues. Synthetic PPAR agonists have exhibited therapeutic benefits in treating diabetes and cardiovascular diseases. The discovery of PPAR-specific ligands has led to significant advancement in our understanding of the structure of these receptor proteins and the molecular mechanism of their ligand-dependent activation. Herein, we present both recent progress in the functional analysis of these orphan receptors and the confirmation of the PPARs as molecular targets for the development of new medicines to treat human metabolic disease.

New synthetic approaches to estrogen receptor modulators: Imidazo[1,2-a]pyridines

Constrained triarenes have been important templates for selective modulation of the estrogen receptor (ER). For our ER program, we sought an unexplored, synthetically accessible heterocyclic template capable of bearing a broad range of pharmacophores. Traditional approaches to these therapeutics such as raloxifene have relied on an alkoxy moiety to link the arene-based scaffold to the modulating amine group. Alternatively, aryl halide-mediated introduction of alkylene or aryl side chains has not been studied extensively. The synthetic incorporation of pharmacophoric side chains that are carbon-linked to a novel imidazopyridine-based ER recognition motif is disclosed.

Tribute to a living legend.

The Editorial Board wishes to dedicate this issue of Medicinal Chemistry to the Editor-in-Chief of the journal, Prof. Dr. Atta-ur-Rahman, FRS, on his 70th birthday. The Editorial Board acknowledges the tremendous achievements of Prof. Rahman in the fields of Organic Chemistry in general and on bioactive natural products in particular. Prof. Rahman’s honors include: the first scientist from the Muslim world to have won the prestigious UNESCO Science Prize (1999) in the 35 year old history of the Prize; elected as Fellow of Royal Society (London) in July 2006; conferred honorary doctorate degrees from many prestigious universities, including the University of Cambridge. On a national level his services are acknowledged in the form of four prestigious civil awards, including these highest national awards: Nishan-e-Imtiaz (2002), Hilal-e-Imtiaz (1998), Sitara-e-Imtiaz (1991) and Tamgha-e-Imtiaz (1983). At an academic level, Prof. Rahman has 856 publications in several fields of organic chemistry including 658 research publications, 21 patents, 114 books and 65 chapters in books published largely by major U.S. and European presses. He is currently the Editor-in-Chief of 12 scientific journals in fields ranging from Medicinal Chemistry to Pharmaceutical Drug Design. Seventy six students have completed their Ph.D. degrees under his supervision. He chairs the Network of Academies of Sciences of Islamic Countries (NASIC) and is the Vice-President (Central & South Asia) of the Academy of Sciences for the Developing World (TWAS) Council, and Foreign Fellow of Korean Academy of Sciences. Prof. Atta-ur-Rahman was the President of the Pakistan Academy of Sciences (2003-2006) and was again elected as the President of the Academy from 1st of January 2011. In particular, Prof. Rahman has made outstanding contribution to Medicinal Chemistry. The contributions of Prof. Rahman to the uplifting of science in Pakistan in his capacity as the Federal Minister for Science & Technology and later as Chairman Higher Education Commission were acknowledged by a high Cilvil Awards of the government of Austria and TWAS prize for institution building as well as by four editorials in Nature. The Editorial board wishes health and prosperity to Prof. Atta-ur-Rahman in the years to come.

Recent Advances in Peroxisome Proliferator- Activated Receptor Science

The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors, a set of three receptor sub-types encoded by distinct genes, function as lipid sensors to regulate a broad range of genes in many metabolically active tissues. Synthetic PPAR agonists have exhibited therapeutic benefits in treating diabetes and cardiovascular diseases. The discovery of PPAR-specific ligands has led to significant advancement in our understanding of the structure of these receptor proteins and the molecular mechanism of their ligand-dependent activation. Herein, we present both recent progress in the functional analysis of these orphan receptors and the confirmation of the PPARs as molecular targets for the development of new medicines to treat human metabolic disease.