| Abstract
| - On the basis of our previous findings that 5‘-O-tritylinosine (KIN59) behaves as an allosteric inhibitor ofthe angiogenic enzyme thymidine phosphorylase (TPase), we have undertaken the synthesis and enzymaticevaluation of a novel series of nucleoside analogues modified at positions 1, 2, or 6 of the purine ring andat the 5‘-position of the ribose moiety of the lead compound KIN59. SAR studies indicate that quite largestructural variations can be performed on KIN59 without compromising TPase inhibition. Thus, incorporationof a cyclopropylmethyl or a cyclohexylmethyl group at position N of 5‘-O-tritylinosine increases the inhibitoryactivity against TPase 10-fold compared to KIN59. Moreover, the trityl group at the 5‘-position of theribose seems to be crucial for TPase inhibition. The here reported results further substantiate that 5‘-O-tritylnucleosides represent a new class of TPase inhibitors that should be further explored in those biologicalsystems where TPase plays an instrumental role (i.e. angiogenesis).
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