Aminoisoxazoline Compounds as Agonists of Alpha7-Nicotinic Acetylcholine Receptors

A compound represented by Formula (I):

• wherein:
• W represents a moiety represented by ring system M-I, M-II, M-III, or M-IV:
• wherein:
• Z1, Z2, Z3, Z4, and Z5independently represent N or CR1;
• with the proviso that no more than two of Z1, Z2, Z3, Z4, and Z5 are N;
• R1 independently represent —H, —D, halogen radical, —CN, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C6-cycloalkyl radical, an unbranched —OC1-C4-alkyl, a branched or cyclic —OC3-C4-alkyl, —N(R2)(R3), —(CO)N(R2)(R3), —NR2(CO)(R3), —SO2C1-C4-alkyl, —SO2N(R2)(R3), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R2)(R3), —N(R2)SO2C1-C4-alkyl, an aryl radical, or a heteroaryl radical;
• or when adjacent members of Z1, Z2, Z3, Z4, and Z5, is (CR1)(CR1), the (CR1)(CR1) may form a cycle such that the adjacent R1 substitutents taken together represents a C3-C4-alkyl di-radical or a (3-4 membered)-heteroalkyl di-radical with at least one ring atom of the (3-4 membered)-heteroalkyl di-radical selected from the group consisting of oxygen, nitrogen, and sulfur, with the proviso that when the at least one ring atom is nitrogen, the nitrogen is substituted with —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, —(CO)-unbranched C1-C4-alkyl, —(CO)-branched C3-C4-alkyl, —(SO2)-unbranched C1-C4-alkyl, or —(SO2)-branched C3-C4-alkyl, and with the further proviso that when the at least one ring atom is sulfur, the sulfur may be independently substituted with 0 to 2 ═O;
• wherein:
• i) the alkyl portion of the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, the unbranched —OC1-C4-alkyl, the branched or cyclic —OC3-C4-alkyl, the —SO2C1-C4-alkyl, the —(CH2)mSO2C1-C4-alkyl, the —N(R2)SO2C1-C4-alkyl, the C3-C4-alkyl di-radical, or the (3-4 membered)-heteroalkyl di-radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR2, —(CH2)mOR2, —N(R2)(R3), —NR2(CO)(R3), —(CH2mN(R2(R3), —SO2C1-C4-alkyl, —SO2N(R2)(R3), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R2)(R3), —N(R2)SO2C1-C4-alkyl, —(CO)(CH2)mR2, —(CO)N(R2)(R3), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and
• ii) the aryl radical or the heteroaryl radical may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —OR2, —(CH2)mOR2, —N(R2)(R3), —NR2(CO)(R3), —(CH2)mN(R2)(R3), —SO2C1-C4-alkyl, —SO2N(R2)(R3), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R2)(R3), —N(R2)SO2C1-C4-alkyl, —(CO)(CH2)mR2, —(CO)N(R2)(R3), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R2 and R3 independently represent —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, or the N(R2)(R3) moiety forms a cycle, wherein R2 and R3 taken together represent a C2-C5-alkyl di-radical or a (3-6 membered)-heteroalkyl di-radical;
• wherein the (3-6 membered)-heteroalkyl di-radical comprises at least one ring atom selected from the group consisting of oxygen, nitrogen, and sulfur, with the proviso that when the at least one ring atom is nitrogen, the nitrogen is independently substituted with —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, —(CO)-unbranched C1 C4 alkyl, —(CO)-branched C3-C4-alkyl, —(SO2)-unbranched C1-C4-alkyl, or —(SO2)-branched C3-C4-alkyl, and with the further proviso that when the at least one ring atom is sulfur, the sulfur may be independently substituted with 0 to 2 ═O;
• wherein the C2-C5-alkyl di-radical or the alkyl portion of said (3-6 membered)-heteroalkyl di-radical may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, an unbranched C1-C4-alkyl radical, or a branched C3-C4-alkyl radical;
• Z6, Z7, Z8, and Z9 independently represent N or CR4;
• with the proviso that no more than two of Z6, Z7, Z6, and Z9 are N;
• R4 independently represents —H, —D, halogen radical, —CN, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3- C6-cycloalkyl radical, a (3-6 membered)-heterocycloalkyl radical, an unbranched —OC1-C4-alkyl, a branched or cyclic —OC3-C4-alkyl, —N(R5)(R6), —(CO)C1-C4-alkyl, —(CO)N(R5)(R6), —NR5(CO)(R6), —SO2C1-C4-alkyl, —SO2N(R5)(R6), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R5)(R6), —N(R5)SO2C1-C4-alkyl, an aryl radical, a heteroaryl radical, or the bond directly attaching the W moiety with the aminoisoxazoline moiety;
• wherein:
• i) the alkyl portion of the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, the (3-6 membered)-heterocycloalkyl radical, the unbranched —OC1-C4-alkyl, the branched or cyclic —OC3-C4-alkyl, the —(CO)C1-C4-alkyl, the —SO2C1-C4-alkyl, the —(CH2)mSO2C1-C4-alkyl, or the —N(R5)SO2C1-C4-alkyl, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR5, —(CH2)mOR5, —N(R5)(R6), —NR5(CO)(R6), —(CH2)mN(R5)(R6), —SO2C1-C4-alkyl, —SO2N(R5)(R6), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R5)(R6), —N(R5)SO2C1-C4-alkyl, —(CO)(CH2)mR5, —(CO)N(R5)(R6), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and
• ii) the aryl radical or the heteroaryl radical may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —OR5, —(CH2)mOR5, —N(R5)(R6), —NR5(CO)(R6), —(CH2)mN(R5)(R6), —SO2C1-C4-alkyl, —SO2N(R5)(R6), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R5)(R6), —N(R5)SO2C1-C4-alkyl, —(CO)(CH2)mR5, —(CO)N(R5)(R6), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R5 and R6 independently represent —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, or the N(R5)(R6) moiety forms a cycle, wherein R5 and R6 taken together represent a C2-C6-alkyl di-radical or a (3-6 membered)-heteroalkyl di-radical;
• wherein the (3-6 membered)-heteroalkyl di-radical comprises at least one ring atom selected from the group consisting of oxygen, nitrogen, and sulfur, with the proviso that when the at least one ring atom is nitrogen, the nitrogen is independently substituted with —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, —(CO)-unbranched C1-C4-alkyl, —(CO)-branched C3-C4-alkyl, —(SO2)-unbranched C1-C4-alkyl, or —(SO2)-branched C3-C4-alkyl, and with the further proviso that when the at least one ring atom is sulfur, the sulfur may be independently substituted with 0 to 2 ═O;
• wherein the C2-C6-alkyl di-radical or the alkyl portion of said (3-6 membered)-heteroalkyl di-radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, an unbranched C1-C4-alkyl radical, or a branched C3-C4-alkyl radical;
• X1 independently represents N or C;
• A1, A2, and A3 independently represent N, —NR7, N(CH2)mR7, O, S, or CR8;
• with the proviso that only one A1, A2, and A3 is NR7, N(CH2)mR7, O, or S;
• with the further proviso that when X1 is N, then A1, A2, and A3 independently represent N or CR8;
• R7 independently represents —H, —D, —SO2(CH2)mR9, —(CO)(CH2)mR9, —(CO)N(R9)(R10), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C6-cycloalkyl radical, a (3-6 membered)-heterocycloalkyl radical, an aryl radical, or a heteroaryl radical;
• wherein the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, or the (3-6 membered)-heterocycloalkyl radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR9, —(CH2)mOR9, —N(R9)(R10), —NR9(CO)(R19), —(CH2)mN(R9)(R10), —SO2C1-C4-alkyl, —SO2N(R9)(R10), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R9)(R10), —N(R9)SO2C1-C4-alkyl, —(CO)(CH2)mR9, —(CO)N(R9)(R10), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and wherein the aryl radical or the heteroaryl radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —OR9, —(CH2)mOR9, —N(R9)(R10), —NR9(CO)(R19), —(CH2)mN(R9)(R10), —SO2C1-C4-alkyl, —SO2N(R9)(R19), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R9)(R10), —N(R9)SO2C1-C4-alkyl, —(CO)(CH2)mR9, —(CO)N(R9)(R10), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R8 independently represents —H, —D, halogen radical, —CN, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C6-cycloalkyl radical, a (3-6 membered)-heterocycloalkyl radical, an unbranched —OC1-C4-alkyl, a branched or cyclic —OC3-C4-alkyl, —N(R9)(R10), —(CO)C1-C4-alkyl, —(CO)N(R9)(R10), —NR9(CO)(R10) —SO2C1-C4-alkyl, —SO2N(R9)(R10), —(CH2)rnSO2C1-C4-alkyl, —(CH2)SO2N(R9)(R10), —N(R9)SO2C1-C4-alkyl, an aryl radical, or a heteroaryl radical;
• wherein:
• i) the alkyl portion of the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, the (3-6 membered)-heterocycloalkyl radical, the unbranched —OC1-C4-alkyl, the branched or cyclic —OC3-C4-alkyl, the —(CO)C1-C4-alkyl, the —SO2C1-C4-alkyl, the —(CH2)mSO2C1-C4-alkyl, or the —N(R9)SO2C1-C4-alkyl, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR9, —(CH2)mOR9, —N(139)(R10), —NR9(CO)(R10), —(CH2)mN(R9)(R10), —SO2C1-C4-alkyl, —SO2N(R9)(R10), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R9)(R10), —N(R9)SO2C1-C4-alkyl, —(CO)(CH2)mR9, —(CO)N(R9)(R10), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and
• ii) the aryl radical or the heteroaryl radical may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —(CH2)mOR9, —N(R9)(R10), —NR9(CO)(R10), —(CH2)mN(R9)(R10), —SO2C1-C4-alkyl, —SO2N(R9)(R10), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R9)(R10), —N(R9)SO2C1-C4-alkyl, —(CO)(CH2)mR9, —(CO)N(R9)(R10), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R9 and R1° independently represent —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, or the N(R9)(R10) moiety forms a cycle, wherein R9 and R10 taken together represent a C2-C6-alkyl di-radical or a (3-6 membered)-heteroalkyl di-radical;
• wherein the (3-6 membered)-heteroalkyl di-radical comprises at least one ring atom selected from the group consisting of oxygen, nitrogen, and sulfur, with the proviso that when the at least one ring atom is nitrogen, the nitrogen is independently substituted with —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, —(CO)-unbranched C1-C4-alkyl, —(CO)-branched C3-C4-alkyl, —(SO2)-unbranched C1-C4-alkyl, or —(SO2)-branched C3-C4-alkyl, and with the further proviso that when the at least one ring atom is sulfur, the sulfur may be independently substituted with 0 to 2 ═O;
• wherein the C2-C6-alkyl di-radical or the alkyl portion of said (3-6 membered)-heteroalkyl di-radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, an unbranched C1-C4-alkyl radical, or a branched C3-C4-alkyl radical;
• X2 independently represents N or C;
• A4, A5, and A6 independently represent N, —NR11, N(CH2)mR11, O, S, or CR12;
• with the proviso that only one A4, A5, and A6 is NR11, N(CH2)mR11, O, or S;
• with the further proviso that when X2 is N, then A4, A5, and A6 independently represent N or CR12;
• R11 independently represents —H, —D, —SO2(CH2)mR13, —(CO)(CH2)mR13, —(CO)N(R13)(R14), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C6-cycloalkyl radical, a (3-6 membered)-heterocycloalkyl radical, an aryl radical, a heteroaryl radical, or the bond directly attaching the W moiety with the aminoisoxazoline moiety;
• wherein the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, or the (3-6 membered)-heterocycloalkyl radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR13, —(CH2)mOR13, —N(R13)(R14), —NR13(CO)(R14), —(CH2)mN(R13)(R14), —SO2C1-C4-alkyl, —SO2N(R13)(R14), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R13)(R14), —N(R13)SO2C1-C4-alkyl, —(CO)(CH2),R13, —(CO)N(R13)(R14), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and wherein the aryl radical or the heteroaryl radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —OR13 —(CH2)mOR13, —N(R13)(R14), —NR13(CO)(R14), —(CH2)mN(R13)(R14) —SO2C1-C4-alkyl, —SO2N(R13)(R14), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R13)(R14), —N(R13)SO2C1-C4-alkyl, —(CO)(CH2)mR13, —(CO)N(R13)(R14), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R12 independently represents —H, —D, halogen radical, —CN, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C6-cycloalkyl radical, a (3-6 membered)-heterocycloalkyl radical, an unbranched —OC1-C4-alkyl, a branched or cyclic —OC3-C4-alkyl, —N(R13)(R14), —(CO)C1-C4-alkyl, —(CO)N(R13)(R14), —NR13(CO)(R14), —SO2C1-C4-alkyl, —SO2N(R13)(R14), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R13)(R14), —N(R13)SO2C1-C4-alkyl, an aryl radical, a heteroaryl radical, or the bond directly attaching the W moiety with the aminoisoxazoline moiety;
• wherein:
• i) the alkyl portion of the unbranched C1-C4-alkyl radical, the branched C3-C4-alkyl radical, the C3-C6-cycloalkyl radical, the (3-6 membered)-heterocycloalkyl radical, the unbranched —OC1-C4-alkyl, the branched or cyclic —OC3-C4-alkyl, the —(CO)C1-C4-alkyl, the —SO2C1-C4-alkyl, the —(CH2)mSO2C1-C4-alkyl, or the —N(R13)SO2C1-C4-alkyl, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, —OR13, —(CH2)mOR13, —N(R13)(R14), —NR13(CO)(R14), —(CH2)mN(R13)(R14), —SO2C1-C4-alkyl, —SO2N(R13)(R14), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R13)(R14), —N(R13)SO2C1-C4-alkyl, —(CO)(CH2)mR13, —(CO)N(R13)(R14), an unbranched C1 C4 alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• and
• ii) the aryl radical or the heteroaryl radical may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, —CN, —OR13, —(CH2),OR13, —N(R13)(R14), —NR13(CO)(R14), —(CH2),N(R13)(R14.,), —SO2C1-C4-alkyl, —SO2N(R13)(R14), —(CH2)mSO2C1-C4-alkyl, —(CH2)mSO2N(R13)(R14), —N(R13)SO2C1-C4-alkyl, —(CO)(CH2)mR13, —(CO)N(R13)(R14), an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, a C1-C4-hydroxyalkyl radical, a C1-C2-haloalkyl radical, or —OC1-C2-haloalkyl radical;
• R13 and R14 independently represent —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, or the N(R13)(R14) moiety forms a cycle, wherein R13 and R14 taken together represent a C2-C6-alkyl di-radical or a (3-6 membered)-heteroalkyl di-radical;
• wherein the (3-6 membered)-heteroalkyl di-radical comprises at least one ring atom selected from the group consisting of oxygen, nitrogen, and sulfur, with the proviso that when the at least one ring atom is nitrogen, the nitrogen is independently substituted with —H, —D, an unbranched C1-C4-alkyl radical, a branched C3-C4-alkyl radical, a C3-C4-cycloalkyl radical, —(CO)-unbranched C1-C4-alkyl, —(CO)-branched C3-C4-alkyl, —(SO2)-unbranched C1-C4-alkyl, or —(SO2)-branched C3-C4-alkyl, and with the further proviso that when the at least one ring atom is sulfur, the sulfur may be independently substituted with 0 to 2 ═O;
• wherein the C2-C6-alkyl di-radical or the alkyl portion of said (3-6 membered)-heteroalkyl di-radical, may be independently substituted with up to 5 radical substituents comprising:
• —D, halogen radical, ═O, an unbranched C1-C4-alkyl radical, or a branched C3-C4-alkyl radical;
• and
• m independently represents an integer from 1 to 6;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that the aminoisoxazoline compound represented by Formula (I) is exclusive of:
• N-phenyl-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(isoquinolin-3-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(benzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(6-methoxybenzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(1H-indazol-3-yl)-4′H-4-azaspiro[bicyclo[2.2.2]octane-2,5′-isoxazol]-3′-amine;
• N-(7-bromopyrrolo[2,1-f][1,2,4]triazin-4-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(4-chlorobenzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(5-chlorobenzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,31-bicyclo[2.2.2]octan]-3-amine;
• N-(6-chlorobenzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(7-chlorobenzo[d]thiazol-2-yl)-4H-1′-azaspiro[isoxazole-5,31-bicyclo[2.2.2]octan]-3-amine;
• N-(benzo[b]thiophen-2-yl)-4H-1-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(benzo[d]oxazol-2-yl)-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(5,6,7,8-tetrahydroisoquinolin-3-y0-4H-1′-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(5-methoxypyrimidin-2-yl)-4H-1-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• N-(furo[3,2-b]pyridin-5-yl)-4H-1-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine;
• and
• N-(furo[2,3-c]pyridin-5-yl)-4H-1-azaspiro[isoxazole-5,3′-bicyclo[2.2.2]octan]-3-amine.