Anabaseine derivatives, pharmaceutical compositions and method of use thereof

1. A compound of the following formula:

or a pharmaceutically acceptable salt thereof, wherein:

Each D is independently selected from the group consisting of C1-C10 alkyl, C1-C10 alkyl substituted with one or more R 8 , C2-C10 alkenyl, C2-C10 alkenyl substituted with one or more R 8 , C2-C10 alkynyl, C2-C10 alkynyl substituted with one or more R 8 , C3-C10 cycloalkyl, C3-C10 cycloalkyl substituted with one or more R 9 , C4-C10 cycloalkenyl, C4-C10 cycloalkenyl substituted with one or more R 9 , 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkyl substituted with one or more R 9 , 4-10 membered heterocycloalkenyl, 4-10 membered heterocycloalkenyl substituted with one or more R 9 , C5-C11 bicycloalkyl, C5-C11 bicycloalkyl substituted with one or more R 9 , C5-C11 bicycloalkenyl, C5-C11 bicycloalkenyl substituted with one or more R 9 , 5-11 membered heterobicycloalkyl, 5-11 membered heterobicycloalkyl substituted with one or more R 9 , 5-11 membered heterobicycloalkenyl, 5-11 membered heterobicycloalkenyl substituted with one or more R 9 , halo, haloalkyl, OR 7 , SR 7 , NR 7 R 7 , C(O)OR 7 , NO 2 , CN, C(O)R 7 , C(O)C(O)R 7 , C(O)NR 7 R 7 , C(O)C(O)NR 7 R 7 , N(R 7 )C(O)R 7 , NR 7 S(O) q R 7 , N(R 7 )C(O)OR 7 , NR 7 C(O)C(O)R 7 , NR 7 C(O)NR 7 R 7 , NR 7 S(O) q NR 7 R 7 , NR 7 S(O) q R 7 , S(O) q R 7 , S(O) q NR 7 R 7 , OC(O)R 7 , aryl and heteroaryl, wherein said aryl and heteroaryl are each optionally substituted with one or more R 11 ;

Each R 7 is independently selected from the group consisting of H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, 3-10 membered heterocycloalkyl, 4-10 membered heterocycloalkenyl, haloalkyl, aryl and heteroaryl, wherein said aryl and heteroaryl are each optionally substituted with one or more R 11 ;

Each R 8 is independently selected from the group consisting of halo, haloalkyl, OR 7 , SR 7 , C(O)R 7 , OC(O)R 7 , C(O)OR 7 , NR 7 R 7 , NO 2 , CN, OC(O)NR 7 R 7 , C(O)NR 7 R 7 , N(R 7 )C(O)R 7 , N(R 7 )(COOR 7 ), S(O) q NR 7 R 7 , C3-C8 cycloalkyl, C4-C10 cycloalkenyl, 3-8 membered heterocycloalkyl, 4-10 membered heterocycloalkenyl, C5-C11 bicycloalkyl, C5-C11 bicycloalkenyl, 5-11 membered heterobicycloalkyl, 5-11 membered heterobicycloalkenyl, aryl and heteroaryl, wherein said aryl and heteroaryl are each optionally substituted with one or more R 11 ;

Each R 9 is independently selected from the group consisting of R 8 , C1-C10 alkyl, C1-C10 alkyl substituted with one or more R 8 , C2-C10 alkenyl, C2-C10 alkenyl substituted with one or more R 8 , C2-C10 alkynyl and C2-C10 alkynyl substituted with one or more R 8 ;

R 10 is aryl or heteroaryl, wherein said aryl and heteroaryl are each optionally substituted with one or more R 11 ;

Each R 11 is independently selected from the group consisting of C1-C10 alkyl, C1-C10 alkyl substituted with one or more R 8 , C2-C10 alkenyl, C2-C10 alkenyl substituted with one or more R 8 , C2-C10 alkynyl, C2-C10 alkynyl substituted with one or more R 8 , C3-C10 cycloalkyl, C3-C10 cycloalkyl substituted with one or more R 9 , C4-C10 cycloalkenyl, C4-C10 cycloalkenyl substituted with one or more R 9 , 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkyl substituted with one or more R 9 , 4-10 membered heterocycloalkenyl, 4-10 membered heterocycloalkenyl substituted with one or more R 9 , C5-C11 bicycloalkyl, C5-C11 bicycloalkyl substituted with one or more R 9 , C5-C11 bicycloalkenyl, C5-C11 bicycloalkenyl substituted with one or more R 9 , 5-11 membered heterobicycloalkyl, 5-11 membered heterobicycloalkyl substituted with one or more R 9 , 5-11 membered heterobicycloalkenyl, 5-11 membered heterobicycloalkenyl substituted with one or more R 9 , halo, haloalkyl, OR 7 , SR 7 , NR 7 R 7 , C(O)OR 7 , NO 2 , CN, C(O)R 7 , C(O)C(O)R 7 , C(O)NR 7 R 7 , N(R 7 )C(O)R 7 , NR 7 S(O) 2 R 7 , N(R 7 )C(O)OR 7 , NR 7 C(O)C(O)R 7 , NR 7 C(O)NR 7 R 7 , NR 7 S(O) q NR 7 R 7 , NR 7 S(O) q R 7 , S(O) q R 7 , S(O) q NR 7 R 7 , OC(O)R 7 , optionally substituted aryl and optionally substituted heteroaryl;

k is an integer from 0 to 4;

Each q is independently 1 or 2.

2. The compound of claim 1 wherein k is 0 or 1.

3. The compound of claim 1 wherein R 10 is selected from the group consisting of 6 membered monocyclic aryl, 5 or 6 membered monocyclic heteroaryl comprising 1-3 heteroatoms, 8-12 membered bicyclic aryl, 8-12 membered bicyclic heteroaryl comprising 1-6 heteroatoms, 11-14 membered tricyclic aryl and 11-14 membered heteroaryl comprising 1-9 heteroatoms, wherein each of said heteroatoms is independently selected from the group consisting of O, N and S and wherein each of said aryl and heteroaryl is optionally substituted with one or more R 11 .

4. The compound of claim 3 wherein R 10 is selected from the group consisting of 6 membered monocyclic aryl and 5 or 6 membered monocyclic heteroaryl comprising 1-3 heteroatoms, wherein each of said heteroatoms is independently selected from O, S and N, and wherein each of said aryl and heteroaryl is optionally substituted with one or more R 11 .

5. The compound of claim 4 wherein the compound is methyl 3-(5-((5,6-dihydro-2-(pyridin-3(4H)-ylidene)methylfuran-2-yl)thiophene-2-carboxylate.

6. The compound of claim 4 wherein R 10 is:

7. The compound of claim 6 wherein there is an R 11 substitution at the 2-position of the phenyl ring.

8. The compound of claim 7 wherein the compound is selected from the group consisting of 3-(3-(2,5-dichlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3,4,5,6-tetrahydro-3-((5-(2-trifluoromethoxy)phenyl)furan-2-yl)methylene)pyridin-2-yl)pyridine, 3-3-((5-(2-chloro-5-(trifluoromethyl)phenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-2-chloro-4-(trifluoromethyl)phenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2,4-dichlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2-fluorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-o-tolylfuran-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2-chlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2-trifluoromethyl)phenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2,4-dimethoxyphenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine and 3-(3-((5-(2-fluoro-3-(trifluoromethyl)phenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine.

9. The compound of claim 6 wherein the compound is selected from the group consisting of 3-(3-((5-phenylfuran-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(4-chlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(3-chlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(3-chloro-4-methoxyphenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(3,5-bis(trifluoromethyl)phenyl)furan-2-yl)methylene-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(5-(4-fluoro-3-(trifluormethyl)phenyl)furan-2-yl)methylene-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3,4,5,6-tetrahydro-3-((5-(2-nitrophenyl)furan-2-yl)methylene)pyridin-2-yl)pyridine, 3-(3,4,5,6-tetrahydro-3-((5-(3-nitrophenyl)furan-2-yl)methylene)pyridin-2-yl)pyridine, 3-(3-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-(5-(4-fluorophenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyridin-2-yl)pyridine, 3-(3-((5-(2-chloro-5-(trifluoromethyl)phenyl)furan-2-yl)methylene)-3,4,5,6-tetrahydropyrdin-2-yl)pyridine, 3-(3,4,5,6-tetrahydro-3-((5,6-(trifluoromethoxy)phenyl)furan-2-yl)methylene)pyridin-2-yl)pyridine and 3-(3-((5-(3-(trifluoromethyl)phenyl)furan-2-yl)methylene-3,4,5,6-tetrahydropyridin-2-yl)pyridine

10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an effective amount of a compound of claim 1 .