Anabaseine derivatives, pharmaceutical compositions and methods of use thereof
View Patent ↗Disclosed are novel anabaseine derivatives that act as agonists of the α7 nAChR. Also disclosed are pharmaceutical compositions, methods of treating inflammatory conditions, methods of treating CNS disorders, methods for inhibiting cytokine release from mammalian cells and methods for the preparation of the novel compounds.
1. The compound of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
R 12 is selected from the group consisting of:
R 13 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 said aryl and heteroaryl are each optionally substituted with one or more R 17 ;
Each R 14 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, aryl, heteroaryl and haloalkyl;
Each R 15 is independently selected from the group consisting of halo, haloalkyl, CF 3 , OCF 3 , OR 14 , SR 14 , C(O)R 14, OC(O)R 14 , C(O)OR 14 , NR 14 R 14 , NO 2 , CN, OC(O)NR 14 R 14 , C(O)NR 14 R 14 , N(R 14 )C(O)R 14 , N(R 14 )(COOR 14 ), S(O) t NR 14 R 14 , 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
Each R 16 is independently selected from the group consisting of R 15 , C1-C10 alkyl, C1-C10 alkyl substituted with one or more R 15 , C2-C10 alkenyl, C2-C10 alkenyl substituted with one or more R 15 , C2-C10 alkynyl and C2-C10 alkynyl substituted with one or more R 15 ;
Each R 17 is independently selected from the group consisting of C1-C10 alkyl, C1-C10 alkyl substituted with one or more R 15 , C2-C10 alkenyl, C2-C10 alkenyl substituted with one or more R 15 , C2-C10 alkynyl, C2-C10 alkynyl substituted with one or more R 16 , C3-C10 cycloalkyl, C3-C10 cycloalkyl substituted with one or more R 16 , C4-C10 cycloalkenyl, C4-C10 cycloalkenyl substituted with one or more R 16 , 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkyl substituted with one or more R 16 , 4-10 membered heterocycloalkenyl, 4-10 membered heterocycloalkenyl substituted with one or more R 16 , C5-C11 bicycloalkyl, C5-C11 bicycloalkyl substituted with one or more R 16 , C5-C11 bicycloalkenyl, C5-C11 bicycloalkenyl substituted with one or more R 16 , 5-11 membered heterobicycloalkyl, 5-11 membered heterobicycloalkyl substituted with one or more R 16 , 5-11 membered heterobicycloalkenyl, 5-11 membered heterobicycloalkenyl substituted with one or more R 16 , halo, CF 3 , OCF 3 , OR 14 , SR 14 , NR 14 R 14 , C(O)OR 14 , NO 2 , CN, C(O)R 14 , C(O)C(O)R 14 , C(O)NR 14 R 14 , C(O)C(O)NR 14 R 14 , N(R 14 )C(O)R 14 , NR 14 S(O) t R 14 , N(R 14 )C(O)OR 14 , NR 14 C(O)R 14 , NR 14 C(O)NR 14 R 14 , NR 14 S(O) t NR 14 R 14 , NR 14 S(O) t R 14 , S(O) t R 14 , S(O) t NR 14 R 14 , OC(O)R 14 , optionally substituted aryl and optionally substituted heteroaryl; and
t is 1 or 2.