The invention provides a compound of the formula: ##STR00001## wherein A is selected from N, CH and CR; R is selected from halogen, optionally substituted alkyl, aralkyl and aryl, OH, NH.sub.2, NHR.sup.1, NR.sup.1R.sup.2 and SR.sup.3; R.sup.1, R.sup.2 and R.sup.3 are each optionally substituted alkyl, aralkyl or aryl groups; B is selected from NH.sub.2 and NHR.sup.4; R.sup.4 is an optionally substituted alkyl, aralkyl or aryl group; X is selected from H, OH and halogen; Z is selected from H, Q, SQ and OQ; Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer, a pharmaceutically acceptable salt, an ester, or a prodrug thereof; with the proviso that the stereochemistry of the aza-sugar moiety is D-ribo or 2'-deoxy-D-erythro-; pharmaceutical compositions comprising said compound; and methods of treatment using said compound.
The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5'-methylthioadenosine phosphorylases (MTAP), 5'-methylthioadenosine mucliosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.
The present invention provides compounds having the formula: ##STR00001## wherein A is CH or N; B is chosen from OH, NH.sub.2, NHR, H or halogen; D is chosen from OH, NH.sub.2, NHR, H, halogen or SCH.sub.3; R is an optionally substituted alkyl, aralkyl or aryl group; and X and Y are independently selected from H, OH or halogen except that when one of X and Y is hydroxy or halogen, the other is hydrogen; and Z is OH or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof; and compounds having the formula: ##STR00002## wherein A, X, Y, Z and R are defined for compounds of formula (I) where first shown above; E is chosen from CO.sub.2H or a corresponding salt form, CO.sub.2R, CN, CONH.sub.2, CONHR or CONR.sub.2; and G is chosen from NH.sub.2, NHCOR, NHCONHR or NHCSNHR; or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester thereof, or a prodrug thereof.The present invention also provides the use of the above compounds as pharmaceuticals, pharmaceutical compositions containing the compounds and processes for preparing the compounds.
A process of preparing a compound of the formula (I) ##STR00001## wherein B is chosen from OH, NH.sub.2, NHR, H or halogen; D is chosen from OH, NH.sub.2, NHR, H halogen or SCH.sub.3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II) ##STR00002## with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX), ##STR00003## to form a compound of formula (XX) ##STR00004## The compound of formula (XX) is N- and O-deprotected to obtain the compound of formula (I).
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