Heteroaryl fused aminoalkyl-imidazole derivatives: selective modulators of GABAa receptors

A compound of the formula:

• 67
• or pharmaceutically acceptable non-toxic salts thereof wherein:
• W represents
• 68
• where Z is O, or S;
• R1 represents phenyl, C1-C6 alkyl, cyclopentyl, cyclohexyl, benzyl, 3-fluorobenzyl, or cyclopropylmethyl;
• R2 represents
• hydroxyl;
• C1-C6 alkyl or C1-C6 alkoxy, each of which are optionally substituted with amino, mono or di(C1-C6) alkylamino, a C5-C7 heterocycloalkyl group where the heteroatom is nitrogen and the nitrogen is attached to the parent alkyl portion;
• O(CH2)nCO2R8 where n=1,2,3,4, NR8COR9, COR8, CONR8R9 or CO2R8 where R8 and R9 are the same or different and represent hydrogen or C1-C6 alkyl;
• or
• NR8R9 forms a 5-, 6-, or 7-membered heterocyclic ring;
• or R2 represents
• hydrogen or
• a group of the formula
• 69
• where
• Rn and Rk independently represent C1-C6 alkyl, C2-C6 alkenyl, C1-C6 cycloalkyl (C1-C6) alkyl, benzoyl where the phenyl portion is optionally substituted with halgoen, C1-C6 alkyl, or C1-C6 alkoxy;
• a group of the formula IV-a
• 70
• where p, s, and t independently represent 1 or 2;
• J is CH, N, O, or a carbon atom substituted with C1-C6 alkyl;
• or
• NRkRn represents
• 71
• where s, t, and J are as defined above;
• R3 represents
• C1-C6 alkyl, allyl, cyclopropylmethyl, cyclopentyl;
• or benzyl optionally mono-, di-, or trisubstituted independently
• with
• halogen, nitro, trifluoromethyl, trifluoromethoxy, cyano, or hydroxy;
• C1-C6 alkyl or C1-C6 alkoxy, each of which is optionally substituted with amino, mono or di(C1-C6) alkylamino, a C5-C7 heterocycloalkyl group where the heteroatom is nitrogen and the nitrogen is attached to the parent alkyl portion;
• O(CH2)nCO2R8 where n=1,2,3,4, NR8COR9, COR8, CONR8R9 or CO2R8 where R8 and R9 are the same or different and represent hydrogen or C1-C6 alkyl;
• NR8R9 forms a 5-, 6-, 7-membered heterocyclic ring;
• SO2R8, NHSO2R8, SO2NHR8, SO2NHCOR8, CONHSO2R8 where R8 is defined as above;
• O(CH2)n G where n=1,2,3,4 and G is SO2R8, NHSO2R8, SO2NHR8, SO2NHCOR8, or CONHSO2R8, where R8 is as defined above;
• or
• tetrazole, triazole, imidazole, thiazole, oxazole, thiophene, or pyridyl;
• R4, R5 and R6 are the same or different and represent hydrogen;
• or
• C1-C4 alkyl or C1-C6 alkoxy, each of which is optionally substituted with amino, mono or di(C1-C6) alkylamino, a C4-C7 heterocycloalkyl group where the heteroatom is nitrogen and the nitrogen is attached to the parent alkyl portion, C1-C6 alkylthiol, or halogen;
• O(CH2)nCO2R8 where n=1,2,3,4, NR8COR9, COR8, CONR8R9 or
• CO2R8 where R8 and R9 are the same or different and represent hydrogen or C1-C6 alkyl;
• NR8R9 forms a 5-, 6-, or 7-membered heterocyclic ring;
• or
• R4 and R5 can form a 1,3-dioxolene ring;
• X represents a bond, CH2, or CHCH;
• and
• A, B, C, and D are the same or different and represent CH or N with the proviso that at least one, but not more than two of A,B,C, or D represent N.