Amino-aza-adamantane derivatives and methods of use
View Patent ↗The invention relates to amine-substituted aza-adamantane derivatives, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. Radiolabelled compounds useful for evaluating the binding affinity to α7 nicotinic acetylcholine receptors also are described.
1. A compound of formula (I)
or a pharmaceutically acceptable salt thereof, wherein
X 1 is a bond;
A is benzofuranyl, benzoxadiazolyl, benzoisoxazole, benzoisothiazole, benzooxazole, 1,3-benzothiazolyl, benzodioxolyl, benzothiophenyl, chromenyl, cinnolinyl, furyl, furopyridine, isoquinolinyl, isobenzofuran, isoxazolyl, isothiazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, oxazolopyridine, pyrazolyl, pyrrolyl, pyridazinyl, pyradinyl, pyrazinyl, pyrimidinyl, quinoxalinyl, quinolinyl, thiazolyl, thienyl, thienopyridine, thiadiazolyl, triazolyl, triazinyl and thienopyridinyl; and
R 1 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl.
2. The compound according to claim 1 , wherein
A is selected from the group consisting of 6-(1,3-benzothiazolyl), 5-benzodioxolyl, 2-benzothiophenyl, 3-benzothiophenyl, 5-benzothiophenyl, 3-chromenyl, 5 -thieno [2,3-c] pyridinyl and 6-thieno [3,2-c] pyridinyl.
3. The compound according to claim 1 , wherein
A is
X 2 is selected from the group consisting of —O—, and —S—;
one of X 4 , X 5 , X 6 and X 7 may be nitrogen and the others are CR a ; and
each occurrence of R a is hydrogen.
4. A compound selected from the group consisting of
benzo [b] thiophene-2-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo [b] thiophene-2-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo [b] thiophene-3-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo [b] thiophene-3-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo [b] thiophene-5-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo [b] thiophene-5-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[2,3-c]pyridine-5-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[2,3-c]pyridine-5-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[3,2-c]pyridine-5-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[3,2-c]pyridine-5-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzothiazole-6-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzothiazole-6-carboxylic acid (4s)-(1-azatricyclo[3.3.1.1 3.7 ]dec-4-yl)-amide;
2-aminobenzothiazole-6-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
furo[2,3-c]pyridine-5-carboxylic acid (1-aza-tricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
3-methyl-benzofuran-2-carboxylic acid (1-aza-tricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
furo[2,3-c]pyridine-5-carboxylic acid (1-aza-tricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzofuran-2-carboxylic acid(4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo[d][1,2,3]thiadiazole-5-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
isoquinoline-3-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
benzo[c][1,2,5]thiadiazole-5-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[3,2-b]thiophene-2-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
thieno[2,3-b]thiophene-2-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
5-chlorobenzofuran-2-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide;
1H-indazole-3-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide; and
1H-indazole-4-carboxylic acid (4r)-(1-azatricyclo[3.3.1.1 3,7 ]dec-4-yl)-amide.