An efficient and rapid microwave-assisted solution-phase method for the synthesis of 2-amino-4-arylpyrimidine-5-carboxylic acid derivatives has been developed. The five-step linear protocol involves an initial Biginelli multicomponent reaction leading to dihydropyrimidine-2-thiones which are subsequently S-alkylated with methyl iodide. The resulting 2-methylthiodihydropyrimidines are sequentially oxidized first with manganese dioxide and then with Oxone to provide 2-methylsulfonyl-pyrimidines which serve as excellent precursors for the generation of a variety of 2-substituted pyrimidines via displacement of the reactive sulfonyl group with nitrogen, oxygen, sulfur, and carbon nucleophiles. A modified protocol using a solid-phase method has also been developed.

A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 μM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 μM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

2-Methylsulfonylpyrimidines (VIII) -readily available from a Biginelli multicomponent strategy as shown for (VIIIa) -undergo displacement of the reactive sulfonyl group with different nitrogen, sulfur, oxygen, and carbon nucleophiles to give a variety of 2-substituted pyrimidines. The use of high-temperature, sealed-vessel microwave irradiation conditions for all steps allows the synthesis of the target compounds in high yields and short reaction times. The thiomethyl intermediate (VI) can be oxidized to the pyrimidinone (XX) or converted into the 2-amino-1,4-dihydropyrimidine (XXI); in the latter case the free base has to be converted into the trifluoroacetate salt prior to the amination reaction. -(MATLOOBI, M.; KAPPE*, C. O.; J. Comb. Chem. 9 (2007) 2, 275-284; Inst. Chem., Karl Franzens Univ. Graz, A-8010 Graz, Austria; Eng.) -Kieslich 32-163

The TALYS code: TALYS is a computer code system Rhenium-186, having a half-life of 90.64 h, is an important radionuclide, used in metabolic radiotherapy and radio immunotherapy. 186 Re hydroxyethylidene diphosphonate (HEDP) is a new compound used for the palliation of painful skeletal metastases. Its production is achieved via charged-particle-induced reactions; the data are available in EXFOR library. For the work discussed in this paper, production of 186 Re was done via nat W(p,n) 186 Re nuclear reaction. Pellets of nat W were used as targets and were irradiated with 15, 17.5, 20, 22.5, 25 MeV proton beams at 5 µA current. The radiochemical separation was performed by the ion exchange chromatography method. The production yield achieved at 25 MeV was 1.91 MBq·µA -1 ·h -1 .Excitation functions for the 186 Re radionuclide, via 186 W(p,n) 186 Re and 186 W(d,2n) 186 Re reactions were calculated by ALICE-ASH and TALYS-1.0 codes to validate and fit the experimental data and to obtain a recommended set of data for 186 W(p,n) 186 Re reaction. Required thickness of the targets was obtained by SRIM code for each reaction.

Microwave-assisted organic synthesis is an enabling technology that has been exploited for a variety of applications including medicinal chemistry/drug discovery projects where speed is often a critical factor. In this review, applications of microwave-assisted organic synthesis employing a parallel processing regime are summarized. Examples include parallel synthesis in domestic microwave ovens, the use of specialized multivessel rotors and microtiter plates in dedicated multimode microwave reactors, and applications of SPOT synthesis on cellulose matrices.