Heterocycles in Medicine

Heterocyclic Chemistry 5th Edition John Joule and Keith Mills 2010 Blackwell Publishing Ltd 

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Although benzofuroxan (Bfx) and furoxan (Fx) were first synthesized over 100 years ago, it was not until the middle of the 20th century that its relevant bioactivities were identified. Bfx s and Fx s relevant biological behaviors convert these systems in one of the most current study heterocycles in medicinal chemistry. Formally, these compounds are 1,2,5-oxadiazole hf-oxide derivatives, specifically Bfx should be named as benzo[l,2-c][l,2,5]oxadiazole 1-oxide and Fx as 1,2,5-oxadiazole 2-oxide, however, the common trivial... 

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. 

Thiophene-containing molecules can be found in both natural products and synthetic chemotherapeutics. Bithiophene 1, a naturally occurring nematocide, is isolated from the roots of Echinops spaerocephalus, whereas tiaprofenic acid, an anti-inflammatory agent, is a synthetic thiophene derivative. Moreover, thiophene is a useful template for four-carbon homologation via reduction [1], as well as a bioisostere of the benzene ring and other heterocycles in medicinal chemistry. 

Due to the importance of this heterocycle in medicinal chemistry, solid-phase synthesis of derivatives based on this condensation reaction have been investigated. The first report in this area uses a sodium benzenesulfinate resin 247 and gives access in five steps and good overall yields to a library of imidazo[l,2- ]pyridines 248 functionalized at C-2 with an enone moiety <2002OL3935>. Later on, the preparation of libraries of compounds related to 250 or 251 from Rink amide resin 249 have been published (Scheme 68) <2003TL6265>. 

Other innovations in this fifth edition are discussions in Chapter 5 of the modem techniques of (i) solid-phase chemistry, (ii) microwave heating and (iii) flow reactors in the heterocyclic context. Reflecting the large part that heterocyclic chemistry plays in the pharmaceutical industry, there are entirely new chapters that deal with Heterocycles in Medicine (Chapter 33) and Heterocycles in Biochemistry Heterocyclic Natural Products (Chapter 32). 

There are many other examples. A study on allergic reactions to sulfa-based dmgs lists 38 sulfonamide nonantibiotic drugs. Based on the rich history of heterocycles in medicine, it is not surprising that sulfonamides dominate to this day. 

Microwave-assisted synthesis of N-heterocycles in medicinal chemistry 13MCC1323. 

Mendgen T, Steuer C, Klein CD. Privileged Scaffolds or Promiscuous Binders A Comparative Study on Rhodanines and Related Heterocycles in Medicinal Chemistry. /. Med. Ghent. 2012, 55, 743-753. 

Chapter 21 introduces aromatic hydrocarbons and their unique chemistry. In another class of aromatic compounds, heteroatoms replace one or more of the ring carbons. These compounds are collectively known as heterocycles or heterocyclic aromatic compounds, and they comprise a class of compounds so large that an entire course is easily built around their chemistry. Heterocycles are seen in several places in this book, including a brief introduction to their nomenclature in Chapter 5 (Section 5.6) and in Chapter 8 (Section 8.9). The most common heterocycles include five- and six-membered monocyclic derivatives that contain nitrogen, oxygen, or sulfur. Several important bicyclic derivatives contain nitrogen. The use of heterocycles in medicine and industry is extensive. This chapter will expand the aromatic chemistry from Chapter 21 and introduce the world of heterocyclic chemistry. 

Dihydro-1,3-oxazine derivatives are important heterocyclics in medicinal chemistry. Maycock et ed. developed a Cu(OAc)2-catalyzed intramolecular synthesis of benzo- or naphtho-2,3-dihydro-l,3-oxazines from tertiary amines through C-H bond oxidative activation and new C-O bond formation (Scheme 8.110). This reaction could be performed in an open vessel without the addition of external oxidants or additives. Moreover, naphthoxazines could be obtained with 100% diastereoselectivity [184]. 

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