Heteroaryl compounds as sodium channel blockers

摘要

The invention relates to aryl substituted compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein Het, G, A, R, and n are defined as set forth in the specification. The invention 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 invention are especially useful for treating pain.;

主权项

1. A compound having the Formula I:or a pharmaceutically acceptable salt, or solvate thereof, wherein:
Het is pyridinyl; G is G1 or G2, wherein
G1 is  and
G2 is R1 and R2 are each independently selected from the group consisting of hydrogen, alkyl, alkylsulfonyl, alkylsulfinyl, alkylcarbonyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, haloalkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxy, haloalkylcarbonyl, and optionally substituted arylcarbonyl; R3 is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, haloalkoxyalkyl, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl; each R is independently alkyl, alkenyl, alkynyl, halogen, hydroxy, cyano, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonylamino, alkylcarbonyloxy, carboxy, aminosulfonyl, alkylsulfonylamino, alkoxycarbonyl, aminocarbonylalkyl, (alkylaminocarbonyl)alkyl, (dialkylaminocarbonyl)-alkyl, —CH(OH)C(═O)NH2, —CH(OH)CH2NRaRb, —CH(NRaRb)CH2OH, or —CH2CH(NRaRb)CH2OH, where Ra and Rb are each independently hydrogen or C1-6 alkyl; n is 0, 1, 2, 3, 4, 5, or 6; A is Aa, Ac, or Ae; Aa is Ac is Ae is R7, R8, R9, R10, R11, and R12 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, haloalkyl, hydroxyalkyl, hydroxy, nitro, amino, cyano, amide, carboxyalkyl, alkoxyalkyl, ureido, acylamino, thiol, acyloxy, azido, mercaptoalkyl, alkoxy, carboxy, and aminocarbonyl; and X is —O—, —S—, —SO—, —SO2—, —CH2—, —NR4—, —N(R5)SO2—, or —SO2N(R6)—, wherein R4, R5, and R6 are each independently hydrogen or alkyl.