Spirocyclic azaadamantane derivatives and methods of use
View Patent ↗The invention relates to compounds that are spirocyclic azaadamantane derivatives derivatives, particularly spirocyclic azaadamantanyl ether or amine derivatives, compositions comprising such compounds, methods of using such compounds and compositions, processes for preparing such compounds, and intermediates obtained during such processes.
1. A compound of formula (I)
or a pharmaceutically acceptable salt or prodrug thereof, wherein
A is N;
X 1 is CR x1 ;
X 2 is CR x2 ;
X 3 is CR x3 ;
X 4 is CR x4 ;
L 1 is —O—;
L 2 is —CH 2 —; and
R x1 , R x2 , R x3 , and R x4 are each independently H, alkyl, aryl, halogen, or heteroaryl.
2. The compound according to claim 1 , wherein at least one R x1 , R x2 , R x3 , and R x4 is
wherein
X 5 is CR x5 or N;
X 6 is CR x6 or N;
X 7 is CR x7 or N;
X 8 is CR x8 or N;
X 9 is CR x9 or N;
X 10 is CR x10 or N;
Y 1 is CR y1 , N; O, or S;
Y 2 is CR y2 , N; O, or S;
Y 3 is CR y3 , N; O, or S;
Y 4 is CR y4 , N; O, or S;
Y 5 is CR y5 , N; O, or S;
R x5 , R x6 , R x7 , R x8 , and R x9 , and R x10 are each independently H, alkyl, aryl, cycloalkyl, halogen, halo alkyl, heteroaryl, OR b , NR d R e , COR b , CN, CO 2 R b , or CONR d R e ;
R y1 , R y2 , R y3 and R y4 are each independently H, alkyl, aryl, cycloalkyl, halogen, halo alkyl, heteroaryl, OR b , NR d R e , COR b , CN, CO 2 R b , or CONR d R e ;
R y5 is H, alkyl, aryl, alkylcarbonyl, alkoxycarbonyl, or heteroaryl; and
R b , R d , and R e are independently H, alkyl, aryl, alkylcarbonyl, alkoxycarbonyl, or heteroaryl.
3. The compound according to claim 2 , wherein,
one of R x2 or R x3 is
4. The compound according to claim 3 , wherein
one of R x2 or R x3 is
5. The compound according to claim 4 , wherein R b is H.
6. A compound of claim 1 , wherein the compound is
3H-(4′s)-1′-azaspiro[benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′s)-1′-azaspiro[5-bromobenzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′s)-1′-azaspiro[5-phenylbenzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′s)-1′-azaspiro[5-(indol-5-yl)-benzofuran-2,4]′-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′s)-1′azaspiro[5-(indol-6-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′s)-1′azaspiro[5-(indol-4-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-1-(4′r)-1′-azaspiro[5-bromobenzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-phenylbenzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-(indol-5-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-(benzo[b]thiophen-5-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-(indol-4-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-(2-oxo-indolin-5-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiro[5-(thiophen-3-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane;
3H-(4′r)-1′-azaspiiro[5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane; or
3H-(4′r)-1′-azaspiro[5-(thieno[2,3-b]pyridin-5-yl)-benzofuran-2,4′]-tricyclo[3.3.1.1 3,7 ]decane.