Blockers of sodium channels.

摘要

A compound represented by the formula: wherein X is hydrogen, halogen, trifluoromethyl, (C1-C8) alkyl, phenyl unsubstituted or substituted with halo, (C1-C8) alkyl-thio, phenyl-C1-C8 alkyl -thio, (C1-C8) alkyl sulfonyl, or phenyl (C1-C8) alkyl sulfonyl; Y is hydrogen, hydroxyl, mercapto, (C1-C8) alkoxy, (C1-C8) alkylthio, halogen, (C1-C8) alkyl, mononuclear aryl unsubstituted or substituted with halo or -N (R2) 2; R1 is hydrogen or (C1-C8) alkyl; each R2 is, independently, -R7, - (CH2) m-OR8, - (CH2) m-NR7R10, - (CH2) n (CHOR8) (CHOR8) n-CH2OR8, - (CH2CH2O) m-R8, - (CH2CH2O) m-CH2CH2NR7R10, - (CH2) nC (= O) NR7R10, - (CH2) n-Z8-R7, - (CH2) m-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, - ( CH2) n-CO2R7, or R3 and R4 are each, independently, hydrogen, a group represented by the formula (A), (C1-C8) alkyl, hydroxy (C1-C8) alkyl, phenyl, phenyl-alkyl (C1-C8), (halophenyl) -C1-C8 alkyl, ((C1-C8) -phenyl alkyl), ((C1-C8) alkoxy-phenyl) -C1-C8 alkyl, naphthyl-alkyl ( C1-C8) or pyridyl-(C1-C8) alkyl, with the proviso that at least one of R3 and R4 is a group represented by the formula (A): in which each RL is, independently, -R7 , - (CH2) n-OR8, -O- (CH2) m-OR8, - (CH2) n-NR7R10, -O- (CH2) m-NR7R10, - (CH2) n (CHOR8) (CHOR8) n- CH2OR8, -O- (CH2) m (CHOR8) (CHOR8) n-CH2OR8, - (CH2CH20) m-R8, -O- (CH2CH2O) m-R8, - (CH2CH2O) m-CH2CH2NR7R10, -O- (CH2CH2O ) m-CH2CH2NR7R10, - (CH2) nC (= O) NR7R10, -O- (CH2) mC (= O) NR7R10, - (CH2) n- (Z) g-R7, -O- (CH2) m- (Z) g- R7, - (CH2) n-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2) m-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, - (CH2) n-CO2R7, -O- (CH2) m-CO2R7, -OSO3H, -O-glucuronide, -O-glucose, or each or is, independently, an integer from 0 to 10; each p is an integer from 0 to 10; with the proviso that the sum of o and p in each adjacent chain varies from 1 to 10; each x is, independently, O, NR10, C (= O), CHOH, C (= N-R10), CHNR7R10, or represents a single bond; R5 is -O- (CH2) m-OR8, - (CH2) n-NR7R10, -O- (CH2) m-NR7R10, - (CH2) n (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2 ) m (CHOR8) (CHOR8) n-CH2OR8, - (CH2CH2O) m-R8, -O- (CH2CH2O) m-R8, - (CH2CH2O) m-CH2CH2NR7R10, -O- (CH2CH2O) m-CH2CH2NR7R10, - ( CH2) nC (= O) NR7R10, -O- (CH2) mC (= O) NR7R10, - (CH2) n- (Z) g-R7, -O- (CH2) m- (Z) g-R7, - (CH2) n-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2) m-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2) m-CO2R7, -OSO3H, -O-glucuronide, -O-glucose, or each R6 is, independently, -R7, -OR11, -N (R7) 2, - (CH2) m-OR8, -O- (CH2) m -OR8, - (CH2) n-NR7R10, -O- (CH2) m-NR7R10, - (CH2) n (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2) m (CHOR8) (CHOR8) n -CH2OR8, - (CH2CH2O) m-R8, -O- (CH2CH2O) m-R8, - (CH2CH2O) m-CH2CH2NR7R10, -O- (CH2CH2O) m-CH2CH2NR7R10, - (CH2) nC (= O) NR7R10, -O- (CH2) mC (= O) NR7R10, - (CH2) n- (Z) g-R7, -O- (CH2) m- (Z) g-R7, - (CH2) n-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, -O- (CH2) m-NR10-CH2 (CHOR8) (CHOR8) n-CH2OR8, - (CH2) n-CO2R7, -O- (CH2) m-CO2R7, - OSO3H, -O-glucuronide, -O-glucose, or in both R6 are -OR11 and are located adjacent to each other in an an illo phenyl, the alkyl moieties of the two R6 can be linked together forming a methylenedioxy group; each R7 is, independently, hydrogen or (C1-C8) alkyl; each R8 is independently hydrogen, (C1-C8) alkyl, -C (= O) -R11, glucuronide, 2-tetrahydropyranyl, or each R9 is independently -CO2R7, -CON (R7) 2 , -SO2CH3, or -C (= O) R7; each R10 is, independently, -H, -SO2CH3, -CO2R7, -C (= O) NR7R9, -C (= O) R7 or -CH2- (CHOH) n-CH2OH; each Z is, independently, CHOH, C (= O), CHNR7R10, C = NR10 or NR10; each R11 is, independently, (C1-C8) alkyl; each g is, independently, an integer from 1 to 6; each m is, independently, an integer from 1 to 7; each n is, independently, an integer from 0 to 7; each Q is C-R5 or C-R6; or a pharmaceutically acceptable salt thereof, and including all enantiomers, diastereomers and racemic mixtures thereof.