Substituted indazoles for targeting Hsp90

1. A compound of formula (I):

A-X 1 -L-X 2 —B   (I)

wherein:

A is a heat shock protein 90 binding component;

X 1 is selected from the group consisting of —NH—, —O—, —S—, —C(O)— and —S(O) 2 —;

X 2 is selected from the group consisting of —NR—, —O—, —S—, —C(O)— and —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;

B is selected from the group consisting of a detection moiety, an anti-cancer agent, and a heat shock protein 90 binding component; and

R is selected from the group consisting of —H and a detection moiety;

wherein each heat shock protein 90 binding component independently has the following formula (II):

wherein:

R 1 and R 2 are independently selected from the group consisting of —H and —C 1-8 -alkyl;

Y is CR 3 or N;

R 3 is —H, —F or —OCH 3 ;

R 4 and R 5 are independently selected from the group consisting of —H, —F and —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 and R 8 are independently selected from the group consisting of —H and —C 1-8 -alkyl;

X is N;

and

represents 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 formula:

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

4. The compound of claim 3 , wherein B is a fluorophore.

5. The compound of claim 1 , wherein B is an anti-cancer agent.

6. The compound of claim 1 , wherein B is a heat shock protein 90 binding component.

7. The compound of claim 1 , wherein:

R 1 and R 2 are independently —H;

Y is CR 3 ;

R 3 is —H;

R 4 and R 5 are independently —H;

R 6 is —C 1-8 -alkyl or halo-C 1-8 -alkyl; and

R 7 and R 8 are independently —C 1-8 -alkyl.

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

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

10. A kit comprising a compound of claim 1 .