NEW ALPHA2 ADRENOCEPTOR AGONISTS

摘要

Compounds of formula (I), wherein X and R1-R6, are as defined in the claims, exhibit alpha2 agonistic activity and thus are useful as alpha2 agonists, especially as alpha2A agonists. Methods of use of said compounds are also provided.

主权项

1. A compound of Formula I, wherein X is O or S; R1 is hydroxy, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, cyclo(C3-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl, cyano, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkoxy, hydroxy(C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C2-C6)alkenyl, (C2-C6)alkenyloxy(C2-C6)alkenyl, halo(C1-C6)alkoxy(C1-C6)alkyl, halo(C1-C6)alkoxy-halo(C1-C6)alkyl, (C1-C6)alkoxy-halo(C1-C6)alkoxy, carboxy, (C1-C6)alkyl-(C═O)—, (C1-C6)alkoxy-(C═O)—, (C1-C6)alkyl-(C═O)—O—, halo(C1-C6)alkyl-(C═O)—, halo(C1-C6)alkoxy-(C═O)—, (R6)2N—, (R6)2N—(C1-C6)alkyl, (R6)2N—(C═O)—, R6—(C═O)—N(R6)—(C═O)—, R6—(O═S═O)—N(R6)—(C═O)—, R6—(C═O)—N(R6)—(O═S═O)—, R6—(O═S═O)—N(R6)—(O═S═O)—, (R6)2N—N—, (R6)N═N—, (R6)2N—O—, (R6)O—N(R6)—, (C1-C6)alkyl-S—, (C2-C6)alkeny-S—(C2-C6)alkenyl, hydroxy(C1-C6)alkyl-S—, hydroxy(C1-C6)alkyl-S—(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl-S—(C1-C6)alkyl, halo(C1-C6)alkyl-S—, halo(C1-C6)alkyl-S—(C1-C6)alkyl, halo(C1-C6)alkyl-S-halo(C1-C6)alkyl, R6—(O═S)—, (R6)2N—(O═S)—, R6—(O═S═O)—, (R6)2N—(O═S═O)—, phenyl, phenyl-O—, heteroaryl, heteroaryl-O—, phenyl-N(R6)—, heteroaryl-N(R6)—, or heteroaryl(C1-C6)alkyl; R2 is H, hydroxy, oxo, fluoro, (C1-C6)alkyl, halo(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, cyclo(C3-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl, cyano, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkoxy, hydroxy(C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C2-C6)alkenyl, (C2-C6)alkenyloxy(C2-C6)alkenyl, halo(C1-C6)alkoxy(C1-C6)alkyl, halo(C1-C6)alkoxy-halo(C1-C6)alkyl, (C1-C6)alkoxy-halo(C1-C6)alkoxy, carboxy, (C1-C6)alkyl-(C═O)—, (C1-C6)alkoxy-(C═O)—, (C1-C6)alkyl-(C═O)—O—, halo(C1-C6)alkyl-(C═O)—, halo(C1-C6)alkoxy-(C═O)—, N(R6)—(C═O)—, R6—(C═O)—N(R6)—(O═S═O)—, R6—(O═S═O)—N(R6)—(O═S═O)—, (R6)2N—N—, (R6)N═N—, (R6)2N—O—, (R6)O═N—, (C1-C6)alkyl-S—, (C2-C6)alkeny-S—(C2-C6)alkenyl, hydroxy(C1-C6)alkyl-S—, hydroxy(C1-C6)alkyl-S—(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl-S—(C1-C6)alkyl, halo(C1-C6)alkyl-S—, halo(C1-C6)alkyl-S—(C1-C6)alkyl, halo(C1-C6)alkyl-S-halo(C1-C6)alkyl, R6—(O═S)—, (R6)2N—(O═S)—, R6—(O═S═O)—, (R6)2N—(O═S═O)—, phenyl, phenyl-O—, heteroaryl, heteroaryl-O—, phenyl-N(R6)—, heteroaryl-N(R6)—, or heteroaryl(C1-C6)alkyl; R3 is H, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, or cyclo(C3-C6)alkyl; R4 is H, hydroxy, halogen, (C1-C2)alkyl, or halo(C1-C2)alkyl; R5 is H, hydroxy, halogen, (C1-C6)alkyl, halo(C1-C2)alkyl, cyclo(C3-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, hydroxy(C1-C6)alkyl, phenyl, or heteroaryl; and R6 is, independently at each occurrence, H, (C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, or R6 and R6 form, together with the atoms they are attached to, a condensed 4, 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4, 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, or halo(C1-C6)alkyl-; or R1 and R2 form, together with the carbon ring atoms to which they are attached, a condensed 4, 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4, 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, or halo(C1-C6)alkyl; or R2 and R3 form, together with the carbon ring atoms to which they are attached, a condensed 4, 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4, 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, or halo(C1-C6)alkyl; or a pharmaceutically acceptable salt or ester thereof.