The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase 1

Variously substituted 7-deazaguanines are of interest as inhibitors of GTP cyclohydrolase I, the first enzyme in the biosynthetic pathway leading to dihydrofolate and tetrahydrobiopterin. Methods are described for the synthesis of 7-deazaguanines substituted at positions 2, 6 and 9 (purine numbering) such that a wide diversity of compounds can be prepared. These methods supplement our previous work that established routes for the synthesis of 7- and 8-substituted 7-deazaguanines. Emphasis is placed on the properties of 2-thioalkyl pyrimidines as intermediates because they provide the basis for a traceless solid-state synthesis of purines, pteridines, and their analogues. Compounds prepared have been assessed in a primary screen for their ability to inhibit GTPCH I and 8-methyldeazaguanine has been shown to be significantly more potent than any inhibitor yet described. Several compounds appeared to undergo transformation by GTPCH I; with the aid of a model reaction, their behaviour can be interpreted in the context of the mechanism of the hydrolytic phase of GTPCH I

Demand patterns for HIV-tests in general practice: information collected by sentinel networks in 5 European countries.

This study describes a 1 year international data collection on the demand pattern for HIV-antibody tests in general practice recorded by 6 sentinel networks in 5 European countries. The purpose of the recording was to evaluate the use of HIV-antibody testing by general practitioners and the demand for testing among the general population. Sentinel networks of general practitioners are a possible and available instrument for monitoring the perception of the HIV-test, and indirectly of the threat of the HIV-epidemic by the public and by the general practitioners (GPs). Differences were found between the countries in the frequency of testing, the person asking the test and the reason for testing. Possible explanatory factors, such as differences in the routine testing of specific groups, differences in the training and in the role of the GP, differences in the characteristics of prevention policy, are discussed. The European comparison also offers the opportunity to reflect on common medical practice in dealing with demands for HIV-tests. (aut. ref.