摘要 |
The present disclosure provides substituted pyridine and pyrimidine compounds of Formula (I): A1-X-A2-Z-R1 (I) and the pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein A, X, A, Z, and R are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain. |
主权项 |
1. A compound having Formula I:
A1-X-A2Z-R1 I or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein: A1 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; X is selected from the group consisting of —O—; —S—; —SO—; —SO2—; —(CR3aR3b)k—; —NR4—; —NR4SO2—; and —SO2NR4—; R3a and R3b are each independently selected from the group consisting of hydrogen or optionally substituted alkyl; R4 is selected from the group consisting of hydrogen and optionally substituted alkyl; k is 0, 1, or 2; A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; Z is selected from the group consisting of: R2a, R2b, and R2c are each independently selected from the group consisting of hydrogen; alkyl; halo; nitro; cyano; hydroxy; amino; alkylamino; dialkylamino; haloalkyl; hydroxyalkyl; alkoxy; haloalkoxy; and alkoxyalkyl; R1 is selected from the group consisting of —C(O)R5; —SO2NR5; and —N(R6)(R7a)(R7b)+A−; R5 is selected from the group consisting of: wherein: R6 is alkyl; R7a is selected from the group consisting of optionally substituted alkyl and hydroxyalkyl; R7b is selected from the group consisting of optionally substituted alkyl and hydroxyalkyl; or R7a and R7b taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered optionally substituted heterocyclo; R7c is selected from the group consisting of optionally substituted alkyl and hydroxyalkyl R8a is selected from the group consisting of hydrogen and optionally substituted alkyl; R8b is selected from the group consisting of hydrogen and optionally substituted alkyl; R9a, R9b, R9c, R9d, R9e, and R9f are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; R10a and R10b are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; L1 is —(CR10aR10b)r—Y—(CR10aR10b)s—; L2 is —(CR10aR10b)t—; L3 is —(CR10aR10b)u—; Y is absent; or Y is selected from the group consisting of optionally substituted cycloalkyl; optionally substituted aryl; and optionally substituted heteroaryl m, n, o, p, r, s, t, and u are each independently 0, 1, 2, or 3; q is 1, 2, or 3; and A is an anionic counter-ion, with the proviso that when Y is absent then the sum of r plus s is 2, 3, 4, 5, or 6; |