Probes for imaging Huntingtin protein

1. A compound of Formula I,

or a pharmaceutically acceptable salt thereof, wherein

L 1 is —CH═CH— or L 1 is absent;

R 1 is chosen from 5-(tert-butoxycarbonyl)-4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl, 2,3-dihydro-1,4,-benzodioxin-6-yl, 5-bromofuran-2-yl, 1-benzofuran-5-yl, 11-methoxy-7-thia-2,5-diazatricyclo[6.4.0.0 2,6 ]dodeca-1(12),3,5,8,10-pentaen-4-yl, and 10-methoxy-7-thia-2,5-diazatricyclo[6.4.0.0 2,6 ]dodeca-1(12),3,5,8,10-pentaen-4-yl;

L 2 is —N(R 4 )—;

R 2 is chosen from

hydrogen,

lower alkyl, and

lower alkyl substituted with lower alkoxy, amino, (alkyl)amino, (dialkyl)amino, or hydroxy;

for each occurrence, R 3 is independently chosen from

halo,

cyano,

lower alkyl optionally substituted with amino, (alkyl)amino, or di(alkyl)amino, and

ethynyl optionally substituted with tri(alkyl)silyl;

R 4 is chosen from hydrogen and lower alkyl; and

m is 0, 1, or 2.

2. The compound of claim 1 , wherein L 1 is absent.

3. The compound of claim 1 , wherein L 1 is —CH═CH—.

4. The compound of claim 1 , wherein R 4 is hydrogen or methyl.

5. The compound of claim 4 , wherein R 2 is chosen from hydrogen, lower alkyl and lower alkyl substituted with hydroxy, lower alkoxy, amino, (alkyl)amino or (dialkyl)amino.

6. The compound of claim 1 , wherein m is 1.

7. The compound of claim 6 , wherein R 3 is chosen from bromo, chloro, fluoro, aminomethyl, 2-(trimethylsilyl)ethynyl, ethynyl, and cyano.

8. The compound of claim 1 , wherein m is 0.

9. A compound, or a pharmaceutically acceptable salt thereof, chosen from:

2-(5-fluoro-1-benzofuran-2-yl)-N-methylimidazo[1,2-a]pyridin-3-amine;

2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-a]pyridin-3-amine;

6-fluoro-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-a]pyridin-3-amine;

7-fluoro-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-c]pyridin-3-amine;

2-(5-methoxy-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-[6-fluoro-3-(methylamino)imidazo[ 1,2-c]pyridin-2-yl]-1-benzofuran-5-ol;

2-(5-methoxy-1-benzofuran-2-yl)-N-(2-methoxyethyl)imidazo[1,2-c]pyridin-3-amine;

2-[7-fluoro-3-(methylamino)imidazo[1,2-c]pyridin-2-yl]-1-benzofuran-5-ol;

2-{3-[(2-hydroxyethyl)amino]imidazo[1,2-c]pyridin-2-yl}-1-benzofuran-5-ol;

2-(5-hydroxy-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-[5-(2-fluoroethoxy)-1-benzofuran-2-yl]-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(4-methoxyphenyl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(6-methoxy-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

7-methoxy-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[ 1,2-c]pyridin-3-amine;

3-(methylamino)-2-[3-(pyridin-3-ylmethoxy)phenyl]imidazo[1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-[4-(pyridin-3-ylmethoxy)phenyl]imidazo[1,2-c]pyridine-7-carbonitrile;

7-chloro-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-c]pyridin-3-amine;

7-bromo-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-c]pyridin-3-amine;

2-(5-methoxy-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-6-carbonitrile;

2-(5-bromo-1-benzofuran-2-yl)-3-(methylamino)imidazo[ 1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-[3-(pyrazin-2-yl)phenyl]imidazo[1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-[4-(pyrazin-2-yl)phenyl]imidazo[1,2-c]pyridine-7-carbonitrile;

2-[(E)-2-(4-methoxyphenyl)ethenyl]-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1-benzofuran-2-yl)-3-[(2-methoxyethyl)amino]imidazo[1,2-c]pyridine-7-carbonitrile;

2-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-bromofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(4-cyanophenyl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(1-benzofuran-5-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-[4-(prop-2-yn-1-yloxy)phenyl]imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-fluoro-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-{3-[(5-methoxypyrazin-2-yl)methoxy]phenyl}-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-{5-[(5-methoxypyrazin-2-yl)methoxy]pyridin-2-yl}-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile;

3-(dimethylamino)-2-(5-methoxy-1-benzofuran-2-yl)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1-methyl-1H-1,3-benzodiazol-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(6-methoxy-1,3-benzothiazol-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1,3-benzoxazol-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1H-1,3-benzodiazol-2-yl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile;

2-(5-methoxy-1-benzofuran-2-yl)imidazo[1,2-a]pyridine-7-carbonitrile;

2-(6-methoxy-1-methyl-1H-1,3-benzodiazol-2-yl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-[5-(pyridin-3-ylmethoxy)-1-benzofuran-2-yl]imidazo[ 1,2-c]pyridine-7-carbonitrile;

3-amino-2-[5-(2-fluoroethoxy)-1-benzofuran-2-yl]imidazo[1,2-c]pyridine-7-carbonitrile;

3-amino-2-(5-methoxy-1-benzofuran-2-yl)imidazo[ 1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1-benzofuran-2-yl)-3-(methoxymethyl)imidazo[1,2-c]pyridine-7-carbonitrile;

3-[(dimethylamino)methyl]-2-(5-methoxy-1-benzofuran-2-yl)imidazo[1,2-c]pyridine-7-carbonitrile;

2-{5-[2-(dimethylamino)ethoxy]-1-benzofuran-2-yl}-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

3-(methylamino)-2-{4-[(pyridin-3-ylmethoxy)methyl]phenyl}imidazo[1,2-a]pyridine-7-carbonitrile;

3-{[2-(dimethylamino)ethyl]amino}-2-(5-methoxy-1-benzofuran-2-yl)imidazo[1,2-c]pyridine-7-carbonitrile

tert-butyl 2-[7-cyano-3-(methylamino)imidazo[1,2-c]pyridin-2-yl]-4H,5H,6H,7H-furo[3,2-c]pyridine-5-carboxylate;

7-(aminomethyl)-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-c]pyridin-3-amine;

3-(methylamino)-2-{3-[(pyridin-3-ylmethoxy)methyl]phenyl}imidazo[1,2-a]pyridine-7-carbonitrile;

2-{4-[(5-methoxypyrazin-2-yl)methoxy]phenyl}-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-{6-[(5-methoxypyrazin-2-yl)methoxy]pyridin-3-yl}-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-(5-methoxy-1-benzofuran-2-yl)-N-methyl-7-[2-(trimethylsilyl)ethynyl]imidazo[1,2-c]pyridin-3-amine;

7-ethynyl-2-(5-methoxy-1-benzofuran-2-yl)-N-methylimidazo[1,2-c]pyridin-3-amine;

2-(4-{[(5-methoxypyridin-2-yl)methyl]amino}phenyl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile;

2-(4-{5H,6H-imidazo[2,1-b][1,3]thiazol-3-ylmethoxy}phenyl)-3-(methylamino)imidazo[1,2-c]pyridine-7-carbonitrile;

2-{10-methoxy-7-thia-2,5-diazatricyclo[6.4.0.0 2,6 ]dodeca-1(12),3,5,8,10-pentaen-4-yl}-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile;

2-{11-methoxy-7-thia-2,5-diazatricyclo[6.4.0.0 2,6 ]dodeca-1(12),3,5,8,10-pentaen-4-yl}-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile; and

2-{5-[(5-methoxypyridin-2-yl)methoxy]pyrazin-2-yl}-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile.