Carbazole and carboline compounds for use in the diagnosis, treatment, alleviation or prevention of disorders associated with amyloid or amyloid-like proteins

1. A compound of formula (II):

and detectably labeled derivatives, stereoisomers, racemic mixtures, pharmaceutically acceptable salts, hydrates, solvates and polymorphs thereof;

wherein

is selected from the group consisting of

wherein

the ring system B can be optionally substituted in any available position of any of its rings by one or more R 3 ;

V is NR b ,

W is selected from the group consisting of CR c and N;

X is N;

R b is selected from the group consisting of hydrogen, alkyl, —(CH 2 CH 2 —O) n —H and —(CH 2 CH 2 —O) n -alkyl, wherein alkyl can be optionally substituted;

R c is selected from the group consisting of hydrogen, alkyl, halogen, wherein alkyl can be optionally substituted;

R d is selected from the group consisting of halogen, H, OH and O-alkyl, wherein alkyl can be optionally substituted;

R f is selected from the group consisting of H and alkyl;

R 14 is selected from the group consisting of hydrogen, —(CH 2 CH 2 —O) n —R f , —(CH 2 CH 2 —O) n —(CH 2 CH 2 )—R d , alkyl, carbocyclyl and heterocyclyl;

for each occurrence, R 3 is independently selected from the group consisting of halogen, —CN, —O—R 10 , —S—R 10 , —NO 2 , —NR 10 R 11 , —CONR 10 R 11 , —N(R 10 )—C(O)—R 11 , —C(O)O—R 10 , —(O—CH 2 CH 2 ) n —R d , —(CH 2 CH 2 —O) n —R f , —(CH 2 CH 2 —O) n —(CH 2 CH 2 )—R d , alkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, heterocyclylalkyl, alkenyl, and alkynyl, wherein alkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, heterocyclylalkyl, alkenyl, and alkynyl can be optionally substituted, or if more than one group R 3 is present and two of the groups R 3 are adjacent, they can optionally be taken together and can form a 5- to 8-membered ring containing carbon atoms and optionally one or more heteroatoms selected from O, S, or N or optionally one or more heteroatom (e.g., N, O and/or S)-containing moieties and wherein the 5- to 8-membered ring may be substituted;

for each occurrence, R 10 and R 11 are each independently selected from the group consisting of: hydrogen, alkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, and heterocyclylalkyl, wherein alkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, and heterocyclylalkyl can be optionally substituted; and

for each occurrence, n is 1 to 5,

and wherein when the compound is detectably labeled, the detectable label is selected from 2 H, 3 H, 18 F, 123 I, 124 I, 125 I, 131 I, 11 C, 13 N, 15 O, and 77 Br or a fluorescent label.

2. The compound according to claim 1 , which is a compound of the formula

wherein B, X and R b are as defined in claim 1 , and all detectably labeled derivatives, stereoisomers, racemic mixtures, pharmaceutically acceptable salts, hydrates, solvates and polymorphs thereof.

3. The compound according to claim 1 , wherein for each occurrence, R 3 is independently selected from the group consisting of halogen, —O—R 10 , —NR 10 R 11 , —(O—CH 2 CH 2 ) n —R d , —(CH 2 CH 2 —O) n —R f , —(CH 2 CH 2 —O) n —(CH 2 CH 2 )—R d , and alkyl, wherein alkyl can be optionally substituted, and wherein R 10 , R 11 , n, R d and R f are as defined in claim 1 ; or

wherein two groups adjacent R 3 are present which form a 5-membered ring containing carbon atoms and optionally one or more heteroatoms selected from O, S, or N or optionally one or more heteroatom (e.g., N, O and/or S)-containing moieties and wherein the 5-membered ring may be substituted.

4. The compound according to claim 1 which is detectably labeled.

5. The compound according to claim 4 , wherein the detectable label is selected from the group consisting of 2 H, 3 H, or 18 F.

6. The compound according to claim 5 wherein the detectable label is 18 F.

7. A method of imaging amyloid and/or amyloid-like protein aggregates, wherein the method comprises the step of administering a compound according to claim 5 to a patient in need thereof.

8. A method of diagnosing a disorder associated with amyloid and/or amyloid-like protein aggregates, particularly wherein the amyloid-like protein is selected from the group consisting of tau, Abeta, alpha-synuclein, Huntingtin, prion, ATTR (transthyretin) or ADan (ADanPP), more preferably tau, wherein the method comprises the step of administering a compound according to claim 5 to a patient in need thereof.

9. The method according to claim 8 , wherein the disorder is a neurological disorder.

10. The method according to claim 8 , wherein the disorder is selected from the group consisting of Alzheimer' s disease (AD), Creutzfeldt-Jacob disease, dementia pugilistica, Down's Syndrome, Gerstmann-Sträussler-Scheinker disease, inclusion-body myositis, prion protein cerebral amyloid angiopathy, traumatic brain injury, amyotrophic lateral sclerosis, Parkinsonism-dementia complex of Guam, non-Guamanian motor neuron disease with neurofibrillary tangles, argyrophilic grain disease, corticobasal degeneration, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with Parkinsonism linked to chromosome 17, Hallervorden-Spatz disease, multiple system atrophy, Niemann-Pick disease type C, pallido-ponto-nigral degeneration, Pick's disease, progressive subcortical gliosis, progressive supranuclear palsy (PSP), subacute sclerosing panencephalitis, tangle only dementia, postencephalitic Parkinsonism, myotonic dystrophy, tau panencephalopathy, AD-like with astrocytes, certain prion diseases (GS S with tau), mutations in LRRK2, Hallervorden-Spatz disease, chronic traumatic encephalopathy, familial British dementia, familial Danish dementia, frontotemporal lobar degeneration, Guadeloupean Parkinsonism, neurodegeneration with brain iron accumulation, SLC9A6-related mental retardation, white matter tauopathy with globular glial inclusions, traumatic stress syndrome, epilepsy, Lewy body dementia (LBD), hereditary cerebral hemorrhage with amyloidosis (Dutch type), mild cognitive impairment (MCI), multiple sclerosis, Parkinson's disease, HIV-related dementia, adult onset diabetes, senile cardiac amyloidosis, endocrine tumors, glaucoma, ocular amyloidosis, primary retinal degeneration, macular degeneration (such as age-related macular degeneration (AMD)), optic nerve drusen, optic neuropathy, optic neuritis, and lattice dystrophy.

11. A compound which is detectably labeled with 18 F and which is selected from

12. A method of imaging amyloid and/or amyloid-like protein aggregates, wherein the method comprises the step of administering a compound according to claim 6 to a patient in need thereof.

13. The method of claim 7 , wherein the imaging amyloid and/or amyloid-like protein aggregates is in the brain or in the eye.

14. The method of claim 12 , wherein the imaging amyloid and/or amyloid-like protein aggregates is in the brain or in the eye.