The present invention comprises a compound of formula I: ##STR1## R.sub.1 of Formula I is substituted amino represented by formula NR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6 are independently selected from the group consisting of hydrogen, C.sub.1-4 alkyl, and unsubstituted amino with the proviso that R.sup.5 and R.sup.6 are not both hydrogen, and further that R.sup.5 and R.sup.6 are not both amino. R.sub.2 and R.sub.3 of Formula I are independently selected from the group consisting of hydrogen; C.sub.1-4 alkyl; amino; substituted or unsubstituted thiol; and halogen. Moreover, R.sub.4 of Formula I is represented by the formula R.sup.12 -X.sup.12 wherein R.sup.12 is a saturated or unsaturated linear hydrocarbon chain of 5-20 carbons optionally containing one or more interruptions within the chain by a heteroatom, and optionally substituted with one or more .dbd.O, or .dbd.S. Finally, X.sup.12 is selected from the group consisting of hydroxy, an aminoalkyl group, and a known amino acid bound by its .alpha.-amino group.
Novel purine compounds of Formula I. ##STR00001## and tautomers, pharmaceutically acceptable salts, and prodrugs thereof, wherein X is S, S(O), or S(O).sub.2; and O is selected from alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl, and heterocyclic, all optionally substituted, are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same.
Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed. ##STR00001##
A compound represented by Formula I, or a polymorph, ester, tautomer, enantiomer, pharmaceutically acceptable salt or prodrug thereof: ##STR00001## wherein: R.sup.1 is halogen, --OR.sup.1, --SR.sup.11 or lower alkyl; R.sup.2 is --NHR.sup.8; R.sup.3 is selected from the group consisting of hydrogen, halogen, --SR.sup.8, --OR.sup.8, --CN, --C(O)R.sup.9, --CO.sub.2H, --NO2, --NR.sup.8R.sup.10, lower alkyl, lower alkenyl, lower alkynyl, lower perhaloalkyl, aryl, heteroaryl, alicyclic and heterocyclic, all optionally substituted, wherein: the aryl, heteroaryl, alicyclic and heterocyclic groups are optionally mono-, bi- or tri-cyclic, R.sup.4 is --CHR.sup.12--, --C(O), --C(S), --S(O)--, or --SO.sub.2--; R.sup.5 is aryl, heteroaryl, alicyclic, or heterocyclic, wherein the aryl group is substituted with 3 to 5 substituents, the heteroaryl group is substituted with 2 to 5 substituents, the alicyclic group is substituted with 3 to 5 substituents, the heterocyclic group is substituted with 3 to 5 substituents.
The present invention provides compounds represented by Formula I. R.sub.0 is selected from hydrogen, halogen, lower alkyl, --SR.sup.8, --OR.sup.8, --CN, and --NHR.sup.8, R.sub.1 is halogen, or lower alkyl; R.sub.2 is --NHR.sup.8; R.sub.3 is selected from the group consisting of hydrogen, halogen, --SR.sup.8, --OR.sup.8, --CN, --C(O)R.sup.9, --C(O)OH, --NO.sub.2, --NR.sup.8R.sup.10, lower alkyl, lower alkenyl, lower alkynyl, lower perhaloalkyl, aryl, heteroaryl, alicyclic and heterocyclic, all optionally substituted, and R.sub.5 is aryl, heteroaryl, alicyclic, or heterocyclic: ##STR00001##
