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 (LXX) is N- and O-deprotected to obtain the compound of formula (I).
This application is continuation of U.S. patent application Ser. No. 09/958,219, filed Apr. 18, 2002, now U.S. Pat. No. 6,693,193 B1, issued Feb. 17, 2004, which is a U.S. National Phase Filing under 35 U.S.C. .sctn.371 of PCT International Application No. PCT/NZ00/00048, filed on Apr. 7, 2000, and claims priority to New Zealand Patent Application No. NZ 336168, filed on Jun. 8, 1999 and New Zealand Patent Application No. NZ 335090, filed on Apr. 8, 1999, the contents of all of which are hereby incorporated by reference in their entirety.
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).
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).
