Probes for imaging huntingtin protein

An imaging agent comprising a compound of Formula II(a),

• or a pharmaceutically acceptable salt thereof, wherein
• m is 0, 1, or 2;
• n is 2;
• X is N;
• for each occurrence, R1 is independently chosen from halo, C1-C6 alkoxy, hydroxy, aryl, heteroaryl, cycloalkoxy, or C1-C6 alkyl, wherein the C1-C6 alkoxy, aryl, heteroaryl, cycloalkoxy, and C1-C6 alkyl are each optionally substituted with one, two, or three groups independently selected from C1-C6 alkoxy, alkenyl, —NR4R5, halo, or heteroaryl optionally substituted with one to three C1-C6 alkoxy;
• R2 is hydrogen or C1-C6 alkyl;
• and
• R3 is aryl, heteroaryl, or heteroaralkyl, each of which is optionally substituted with one, two, or three groups independently chosen from hydroxy, C1-C6 alkoxy optionally substituted with C1-C6 alkoxy or halo, C1-C6 alkyl optionally substituted with halo, halo, heteroaryl, —(CH2)tNR4R5, cyano, or —C(O)—NR4R5;
• t is 0, 1, or 2;
• each R4 is independently chosen from hydrogen or C1-C6 alkyl;
• each R5 is independently chosen from hydrogen or C1-C6 alkyl;
• or
• R4 and R5 taken together with the nitrogen to which they are bound form a heterocycloalkyl ring, optionally substituted with one, two, or three groups independently chosen from hydroxy, C1-C6 alkoxy, C1-C6 alkyl, halo, or —C(O)—NR6R7;
• each R6 is independently chosen from hydrogen or C1-C6 alkyl;
• and
• each R7 is independently chosen from hydrogen or C1-C6 alkyl;
• wherein the compound of Formula II(a), or a pharmaceutically acceptable salt thereof, is labeled with one or more positron-emitting radionuclides.

An imaging agent comprising a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from

• N-(6-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-fluoropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(pyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[6-(methylcarbamoyl)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-oxo-1,6-dihydropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(pyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyanopyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(2-methoxypyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(5,6-dimethoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-11-{1-methyl-1H,4H,5H,6H-pyrrolo [3 ,4-c]pyrazole-5-carbonyl}-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene;
• 4-methoxy-N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[6-(1H-imidazol-1-yl)pyridin-3-yl]-5-methoxy-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyanopyridin-4-yl)-5-methoxy-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyano-2-methoxypyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(6-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-2-oxo-1,2-dihydropyrimidin-5-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N,5-bis(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N,4-bis(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[5-(2-methoxyethoxy)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• and
• N-[6-(2-methoxyethoxy)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• wherein the compound, or pharmaceutically acceptable salt thereof, is labeled with one or more positron-emitting radionuclides.

A compound selected from

• N-(6-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-fluoropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(pyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[6-(methylcarbamoyl)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-oxo-1,6-dihydropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2 (7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(pyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyanopyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(2-methoxypyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(5,6-dimethoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-11-{1-methyl-1H,4H,5H,6H-pyrrolo [3 ,4-c]pyrazole-5-carbonyl}-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene;
• 4-methoxy-N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[6-(1H-imidazol-1-yl)pyridin-3-yl]-5-methoxy-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyanopyridin-4-yl)-5-methoxy-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(6-oxo-1,6-dihydropyridazin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(3-cyano-2-methoxypyridin-4-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• 5-methoxy-N-(6-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-(1-methyl-2-oxo-1,2-dihydropyrimidin-5-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N,5-bis(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N,4-bis(5-methoxypyridin-3-yl)-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• N-[5-(2-methoxyethoxy)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• and
• N-[6-(2-methoxyethoxy)pyridin-3-yl]-1,8,10-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8,10,12-hexaene-11-carboxamide;
• or a pharmaceutically acceptable salt thereof.