Current Medicinal Chemistry (v.23, #18)

Meet Our Editorial Board Member by Terrence R. Burke (1801-1801).

In this review we discuss drug design strategies directed to the development of potential anti-influenza A(H1N1) inhibitors of M2 ion channel, neuraminidase (NA), hemagglutinin (HA) and RNA-dependent RNA-polymerase complex (RdRp) major targets, following temporal chronology of their findings. Besides searching for new chemotypes, eventually active against new targets of influenza A (H1N1), the design of optimized analogues of proven drugs is largely pursued, taking into account the emerging insight into the mechanisms of resistance to existing antivirals. Computational studies are also summarized, in order to highlight the structural requirements for further chemical optimizations.

The development of reversibly binding radioligands for imaging brain proteins in vivo, such as enzymes, neurotransmitter transporters, receptors and ion channels, with positron emission tomography (PET) is keenly sought for biomedical studies of neuropsychiatric disorders and for drug discovery and development, but is recognized as being highly challenging at the medicinal chemistry level. This article aims to compile and discuss the main considerations to be taken into account by chemists embarking on programs of radioligand development for PET imaging of brain protein targets.

Monocyclic and Fused Azines and Azoles as Histamine H4 Receptor Ligands by Dorota La|ewska, Enrique Domínguez-Álvarez, Katarzyna Kami|ska, Kamil Kuder, Katarzyna Kie|-Kononowicz (1870-1925).
The histamine H4 receptor has stood out since its discovery and identification in 2000 as an important target in the search for potential new drugs for the treatment of inflammatory and allergic diseases such as rhinitis, pruritus and asthma. Thus, in the last decade, both industry and academia have performed an intensive and productive search for new ligands of this newest subtype of histamine receptor. The most promising compounds found include monocyclic and fused azines, and azoles such as bispyrimidines, di- and triaminopyrimidines, quinazolines, imidazoles, indoles, benzimidazoles and benzazoles. The aim of this review is to give an insight into the current state of the art in the field of histamine H4 receptor research, focusing mainly on the last five years.

Impact of Macrophages in Atherosclerosis by Xinjie Lu (1926-1937).
Atherosclerosis is driven by inflammation, with a strong involvement of innate immunity, and involves an expansion of the arterial intima, a normally small area composed of several cell types including smooth muscle cells, lipids, monocytes, macrophages, dendritic cells, and extracellular matrix. Macrophages derived from recruited monocytes are predominant innate immune cells that play crucial roles in the formation of atherosclerotic lesions. Human atherosclerotic plaques have shown that macrophage subsets within a plaque might be more useful for explaining plaque phenotype than just simply giving the total number of macrophages. Therefore, recognizing the roles of macrophage subsets in atherosclerotic plaque formation, progression, and regression would be most helpful for identification of novel strategies to stabilize, or attenuate atherosclerotic lesions. This review discusses the impact of macrophage subsets and their roles in atherosclerosis.