Substituted 6-aminopurines for targeting HSP90

1. A compound of formula (I):

wherein:

A is a heat shock protein 90 binding component of formula (III):

wherein:

R is alkylenyl or heteroalkylenyl;

each Y 1 is independently —CH or —N;

each Z 1 is taken together with the carbon atoms to which they are attached to form a heterocyclic ring;

Z 2 is —H or halo;

Z 3 is —CH 2 —, —S—, —O—or —NH—;

Z 4 is —H or halo; and

is the point of attachment in formula (I);

X 1 is —NH—, —O—, —S—, —C(O)—or —S(O) 2 —;

L is a divalent linker of the following formula:

—(CH 2 ) m —(OCH 2 CH 2 ) n —O—(CH 2 ) p —,

wherein:

m is 2 or 3;

n is 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and

p is 2 or 3;

X 2 is —NR—, —O—, —S—, —C(O)—or —S(O) 2 —;

R is —H or a detection moiety; and

B is a detection moiety, an anti-cancer agent, or a heat shock protein 90 binding component of formula (II):

wherein:

R 1 is —H or —C 1-8 -alkyl;

R 2 is —H or —C 1-8 -alkyl;

Y is —CR 3 or —N;

R 3 is —H, —F or —OCH 3 ;

R 4 is —H, —F or —OCH 3 ;

R 5 is —H, —F or —OCH 3 ;

R 6 is —C 1-8 -alkyl, —C 2-8 -alkenyl, —C 2-8 -alkynyl, —C 3-8 -cycloalkenyl, —C 3-8 -cycloalkenyl-C 1-8 -alkyl, —C 3-8 -cycloalkyl, —C 3-8 -cycloalkyl-C 1-8 -alkyl, aryl, aryl-C 1-8 -alkyl, halo-C 1-8 -alkyl, heteroaryl, heteroaryl-C 1-8 -alkyl, heterocyclyl, heterocyclyl-C 1-8 -alkyl, or hydroxy-C 1-8 -alkyl;

R 7 is —H or —C 1-8 -alkyl;

R 8 is —H or —C 1-8 -alkyl; or

R 7 and R 8 , taken together with the carbon atom to which they are attached, form a —C 3-8 -cycloalkyl;

X is —CR 9 or —N;

R 9 is —H or —C 1-8 -alkyl; and

is the point of attachment in formula (I); or

B is a detection moiety, an anti-cancer agent, or a heat shock protein 90 binding component of formula (III):

wherein:

R is alkylenyl or heteroalkylenyl;

each Y 1 is independently —CH or —N;

each Z 1 is taken together with the carbon atoms to which they are attached to form a heterocyclic ring;

Z 2 is —H or halo;

Z 3 is —CH 2 —, —S—, — 0 —or —NH—;

Z 4 is —H or halo; and

is the point of attachment in formula (I);

wherein each detection moiety independently comprises a fluorophore or a radioactive compound;

wherein the fluorophore is a fluorescein, a rhodamine, a coumarin, a cyanine or a boron-dipyrromethene;

wherein the radioactive compound is a radioisotope; and

wherein the anti-cancer agent is an alkylating agent, an anti-epidermal growth factor receptor antibody, an anti-Her-2 antibody, an antimetabolite, a vinca alkaloid, an anthracycline, a platinum-based agent, a topoisomerase inhibitor, a taxane, an anti-cancer antibiotic, an immune cell antibody, an interferon, an interleukin, a heat shock protein 90 inhibitor, an anti-androgen, an anti-estrogen, an antihypercalcemia agent, an apoptosis inducer, an aurora kinase inhibitor, a Bruton's tyrosine kinase inhibitor, a calcineurin inhibitor, a Ca 2+ -calmodulin-dependent protein kinase II inhibitor, a CD45 tyrosine phosphatase inhibitor, a cell division cycle 25 phosphatase inhibitor, a checkpoint kinase inhibitor, a cyclooxygenase inhibitor, a cRAF kinase inhibitor, a cyclin dependent kinase inhibitor, a cysteine protease inhibitor, a deoxyribonucleic acid intercalator, a deoxyribonucleic acid strand breaker, an E3 ligase inhibitor, an epidermal growth factor pathway inhibitor, a farnesyltransferase inhibitor, a fetal liver kinase-1 inhibitor, a glycogen synthase kinase-3 inhibitor, a histone deacetylase inhibitor, an I-kappa B-alpha kinase inhibitor, an imidazotetrazinone, an insulin tyrosine kinase inhibitor, a c-Jun N-terminal kinase inhibitor, a mitogen-activated protein kinase inhibitor, a mouse double minute 2 inhibitor, an MEK inhibitor, a matrix metalloproteinase inhibitor, a mammalian target of rapamycin inhibitor, a nerve growth factor receptor tyrosine kinase inhibitor, a p38 mitogen-activated protein kinase inhibitor, a p56 tyrosine kinase inhibitor, a platelet-derived growth factor pathway inhibitor, a phosphatidylinositol 3-kinase inhibitor, a phosphatase inhibitor, a protein phosphatase inhibitor, a protein kinase C inhibitor, a protein kinase C delta kinase inhibitor, a polyamine synthesis inhibitor, a protein tyrosine phosphatase 1B inhibitor, a protein tyrosine kinase inhibitor, an SRC family tyrosine kinase inhibitor, a spleen tyrosine kinase inhibitor, a Janus tyrosine kinase inhibitor, a retinoid, a ribonucleic acid polymerase II elongation inhibitor, a serine/threonine kinase inhibitor, a sterol biosynthesis inhibitor, a vascular endothelial growth factor pathway inhibitor, alitretinon, altretamine, aminopterin, aminolevulinic acid, amsacrine, asparaginase, atrasentan, bexarotene, carboquone, demecolcine, efaproxiral, elsamitrucin, etoglucid, a Gliadel implant, hydroxycarbamide, leucovorin, lonidamine, lucanthone, masoprocol, methyl aminolevulinate, mitoguazone, mitotane, oblimersen, omacetaxine, pegaspargase, porfimer sodium, prednimustine, sitimagene ceradenovec, talaporfin, temoporfin, trabectedin or verteporfin.

2. The compound of claim 1 , wherein A has the following formula:

3. The compound of claim 1 , wherein B is the detection moiety.

4. The compound of claim 1 , wherein B is the detection moiety comprising the fluorophore.

5. The compound of claim 4 , wherein B has the following formula:

and

is the point of attachment to the —X 2 -L-X 1 -A moiety of the compound of formula (I).

6. The compound of claim 4 , wherein the fluorophore is a fluorescein.

7. The compound of claim 1 , wherein B is the anti-cancer agent.

8. The compound of claim 7 , wherein the anti-cancer agent is methotrexate, topotecan, irinotecan, etoposide, teniposide, lamellarin D, SN-38, camptothecin, belotecan, rubitecan, thalidomide, or verteporfin.

9. The compound of claim 1 , wherein B is the heat shock protein 90 binding component of formula (II) or formula (III).

10. The compound of claim 9 , wherein B is the heat shock protein 90 binding component of formula (II).

11. The compound of claim 9 , wherein B is the heat shock protein 90 binding component of formula (III).

12. The compound of claim 1 , wherein m is 3 and p is 3.

13. The compound of claim 1 , wherein n is 4.

14. A kit comprising a compound of claim 1 .