Microwave , medicine

In the 1990s the technique of solid-phase organic synthesis (SPOS) became generally popular, but especially in the medicinal chemistry community, for lead detection and lead optimization via combinatorial techniques. The combination with microwave irradiation brought an elegant solution for the problem of the notoriously slower reactions compared to those in solution phase. 

The imidazole ring is a privileged structure in medicinal chemistry since it is found in the core structure of a wide range of pharmaceutically active compounds efficient methods for the preparation of substituted imidazole libraries are therefore of great interest. Recently, a rapid synthetic route to imidazole-4-carboxylic acids using Wang resin was reported by Henkel (Fig. 17) [64]. An excess aliphatic or aromatic amine was added to the commercially available Wang-resin-bound 3-Ar,M-(dimethylamino)isocyano-acrylate, and the mixture was heated in a sealed vial with microwave irradi-... 

From a medicinal chemist s point of view, oxadiazoles are among the most important heterocycles as they are one of the most commonly used bioisosters for amide and ester groups [67]. As such it is hardly surprising that the two regioisomeric oxadiazole scaffolds received the most interest in the field of microwave-assisted synthesis using polymer-supported reagents. 

Kappe CO, Stadler A (2005) Microwaves in organic and medicinal chemistry. Wiley, Weinheim... 

Swamy KMK, Yeh W-B, Lin M-J, Sun C-M (2003) Curr Med Chem 10 2403 CarUlo JR, Dfaz-Ortiz A, de la Hoz A, Moreno A, Gomez MV, Prieto P, Sanchez-Migalldn A, Vazquez E (2003) In Attanasi OA, Spinelli D (eds) Targets in heterocyclic systems, chemistry and properties. Italian Society of Chemistry, vol 7 Baxendale IR, Lee A-L, Ley SV (2005) In Tierney JP, Lidstrom P (eds) Microwave assisted organic synthesis, chap 6. Blackwell Publishing Ltd, Oxford, UK Kappe CO, Stadler A (2005) Microwaves in organic and medicinal chemistry, chap 7. Wiley, Weinheim... 

In the frame of a medicinal project at J J Pharmaceutical Research and Development aimed at designing new potent and selective glycogen synthase kinase-3/i (GSK-3/3) inhibitors, the C-3 derivatization of the 1-methyl-4-[l-alkyl-lff-indol-3-yl]-lff-pyrrole-2,5-dione scaffold was explored [31]. Microwave-assisted Stille reaction of 3-chloro-l-methyl-4-[l-alkyl-lff-indol-3-yl]-lH-pyrrole-2,5-diones with (2,4-dimethoxy-5-pyrimidinyl)(tributyl) stannane at 200 °C yielded in 6 min the desired 3,4-diaryl-lff-pyrrole-2,5-diones in moderate yields (Scheme 12). 

The availability of functionalized 2(lH)-pyrazinone in combination with the use of microwave accelerated solid-phase chemistry constitutes a sohd foundation for generating large libraries of compoimds suitable for medicinal chemistry. The authors have also shown that the scaffold can be further functionalized using the principles of cUck-chemistry , thereby paving the way towards highly substituted 2-pyridone structures [45-47]. 

A semiconductor microcircuit is a series of electrically intercoimected films that are laid down by chemical reactions. The successful growth and manipulation of these films depend heavily on proper design of the chemical reactors in which they are laid down, the choice of chemical reagents, separation and purification steps, and the design and operation of sophisticated control systems. Microelectronics based on microcircuits are commonly used in such consumer items as calculators, digital watches, personal computers, and microwave ovens and in information processing units that are used in communication, defense, space exploration, medicine, and education. 

Microwaves in Organic and Medicinal Chemistry. C. Oliver Kappe, Alexander Stadler Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31210-2... 

Today, a large body of work on microwave-assisted synthesis exists in the published and patent literature. Many review articles [8-20], several books [21-23], and information on the world-wide-web [24] already provide extensive coverage of the subject. The goal of the present book is to present carefully scrutinized, useful, and practical information for both beginners and advanced practitioners of microwave-assisted organic synthesis. Special emphasis is placed on concepts and chemical transformations that are of importance to medicinal chemists, and that have been reported in the most recent literature (2002-2004). The extensive literature survey is limited to reactions that have been performed using controlled microwave heating conditions, i.e., where dedicated microwave reactors for synthetic applications with adequate... 

In more recent work by other researchers, sealed-vessel microwave technology has been utilized to access valuable medicinally relevant heterocyclic scaffolds or intermediates (Scheme 6.120) [240-245]. Additional examples not shown in Scheme 6.120 can be found in the most recent literature (see also Scheme 6.20) [246-249]. Examples of nucleophilic aromatic substitutions in the preparation of chiral ligands for transition metal-catalyzed transformations are displayed in Scheme 6.121 [106,108]. 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

Utilizing the same aryl fluoride linker on conventional MeOPEG polymer, these authors also presented a microwave-accelerated liquid-phase synthesis of benzimidazoles (Scheme 7.70) [79]. This bicydic pharmacophore is an important and valuable structural element in medicinal chemistry, showing a broad spectrum of pharmacological activities, such as antihistaminic, antiparasitic, and antiviral effects. 

C. O. Kappe, A. Stadler Microwaves in Organic and Medicinal Chemistry... 

Microwaves in Organic and Medicinal Chemistry is the very first monograph on this topic, which deals not only with mere synthetic applications of microwave... 

---