| 摘要 |
In one aspect, the present disclosure provides indazoles of Formula I: (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R3, R4, R5, R6, Z1, Z2, Z3, and G are defined as set forth in the specification. Further, the present disclosure also provides compounds of Formulae II and IA, and the pharmaceutically acceptable salts and solvates thereof. The present disclosure is also directed to the use of compounds of Formulae I, II, and IA, and the pharmaceutically acceptable salts and solvates thereof, to treat a disorder responsive to the blockade of sodium channels. In one embodiment, compounds of the present disclosure are especially useful for treating pain.; |
| 主权项 |
1. A compound having Formula I: or a pharmaceutically acceptable salt or solvate thereof,wherein:
Z1, Z2, and Z3 are each independently selected from the group consisting of N and CR11; with the proviso that at least one of Z1, Z2, and Z3 is N; G is selected from the group consisting of cyano, dihydroxyalkyl and —(CHR1a)m—C(═O)E; m is 0, 1, or 2; each R1a is independently selected from the group consisting of hydrogen and hydroxy; E is selected from the group consisting of hydroxy, alkoxy, hydroxyalkyl, and —NR1R2; R1 is selected from the group consisting of hydrogen, alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (carboxamido)alkyl, (cyano)alkyl, alkoxyalkyl, hydroxyalkyl, and heteroalkyl; R2 is selected from the group consisting of hydrogen and alkyl; or R1 and R2 taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo; R3 is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, aminoalkyl, (alkylamino)alkyl, and (carboxamido)alkyl; R4 is selected from the group consisting of hydrogen, alkyl, halogen, cyano, haloalkyl, haloalkoxy, alkoxy, (amino)alkyl, (heterocyclo)alkyl, (heterocyclo)carbonyl, carboxamido, sulfonamido, hydroxyalkyl, carboxy, and optionally substituted heteroaryl; R5 is selected from the group consisting of hydrogen, halo, alkyl, hydroxyalkyl, alkenyl, cyano, heterocyclo, and —X—R7; R6 is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, and cyano; X is selected from the group consisting of —O—, —NR8a—, and —(CH2)t—Y—; Y is selected from the group consisting of —O— and —NR8b—; t is 1 or 2; R7 is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, R8a is selected from the group consisting of hydrogen and alkyl; R8b is selected from the group consisting of hydrogen and alkyl; or R8b and R7 taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo; R9 is selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl; R10a and R10b are independently selected from the group consisting of hydrogen and alkyl; or R10a and R10b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo; and R11 is selected from the group consisting of hydrogen, alkyl, halogen, cyano, haloalkyl, haloalkoxy, and alkoxy. |
