Medicine nitrogen heterocycles

In the construction of C=N bond-containing compounds, such as nitrogen heterocycles, the aza-Wittig methodology has received increased attention as the method of choice [7]. Thus, an easy access to optically active (-)-vasicinone (7-15), a pyr-rolo[2,l-fc]quinazoline alkaloid which is used in indigenous medicine [8], was... 

The recent impact of solid-phase synthesis on medicinally relevant benzoaime-lated nitrogen heterocycles has been recently reviewed [16], therefore in this section only recent publications are included. Benzoannelated heterocycles can be prepared efficiently through cyclization on solid supports employing classical heterocycle forming reactions such as the Fischer [425], the Bischler-Napieralski [426], Tsuge [427], Nenitzescu [428], and Richter [140] reactions. In addition, the... 

More than 50% of all known organic compounds are heterocyclic compounds. They play important roles in medicine and biological systems. A great majority of important drugs and natural products, e.g. caffeine, nicotine, morphine, penicillins and cephalosporins, are heterocyclic compounds. The purine and pyrimidine bases, two nitrogenous heterocyclic compounds, are structural units of RNA and DNA. Serotonin, a neurotransmitter found in our body, is responsible for various bodily functions. 

Arylamines are commonplace, as components of molecules with medicinally or electronically important, catalytic active, or structurally interesting properties. An aryl-nitrogen linkage is included in nitrogen heterocycles such as indoles [4,5] and benzopyrazoles, conjugated polymers such as polyanilines [6-12], and readily oxidized triarylamines used in electronic applications such as 4,4 -bis(3-methylphe-... 

Brase, S., Gil, C., Knepper, K. The recent impact of solid-phase synthesis on medicinally relevant benzannelated nitrogen heterocycles. Bioorg. Med. Chem. 2002, 10, 2415-2437. 

Aran, Goya, and Ochoa (Institute of Medicinal Chemistry, Madrid, Spain) contribute the first comprehensive review of heterocycles containing the sulfamide moiety, covering a wide diversity of heterocyclic ring systems. The chapter by Comins and O Connor, on regioselective substitution in aromatic six-membered nitrogen heterocycles, describes exciting work contributed by their laboratory and also includes a broad literature survey. 

Heterocyclic compounds are ubiquitous in biology, medicine, and biochemistry, and the azoles form an important class of nitrogen heterocyclic compounds with five-membered aromatic rings that can contain one to five nitrogen atoms (other heteroatoms can also be present). Many drugs and pharmaceuticals are derived from azole structures. The structures of representative azoles are shown in Figure 6.1. Note that some of these compounds exist in tautomeric equilibrium in solution. 

In recent years, direct amination of tautomerizable heterocycles with amines via phosphonium coupling has been widely utilized in the synthesis of various heterocychc compounds used for chemical building blocks or medicinal chemistry. The reaction rate of the direct amination is usually dependent upon the electronic and steric nature of the amine nucleophiles. In principle, electron-richer and sterically less-hindered alkyl amines are much more reactive than aryl amines and nitrogen heterocycles (04AP702,05JOC1957). 

Until now, several types of polycyclic aromatic nitrogen heterocycles have been known. In fact, heterocyclic synthesis plays an important role in modern life. Among the nitrogen heterocycles, quinoxaline and phenazine derivatives have attracted great interest because of their wide application in organic and medicinal chemistry. Many phenazine compounds are found in nature and are produced by bacteria. Quinoxalines are the fundamental components of several pharmacological active compounds and some antibiotics such as levomycin, echinomycin, and actinomycin (Bailly et al, 1999 Dell et al, 1975). 

Many nitrogen heterocycles play a role in medicine. One leading actor in this field is morphine. 

Prior to the discovery of niacin receptors, medicinal chemistry efforts were mainly directed toward small heterocyclic carboxylic acids that are structurally similar to niacin. Systematic study of nitrogen-containing five- and six-membered heterocyclic carboxylic acids revealed that activity at GPR109A was significantly reduced for any of the variants of niacin shown in general structures (A and B) [45,46]. These heterocycles include pyrazole, isoxazole, thiazole, pyrazine, and pyrimidine. 

This review chapter focuses on the syntheses and reactions of these 5-membered heterocyclic ring systems containing nitrogen and sulfur (or selenium) (reported during 2006). The importance of these 71-rich heterocycles in medicinal chemistry and natural products is also covered. 

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