Sodium channel blockers

A method of effecting in a subject at least one member selected from the group consisting of promoting hydration of mucosal surfaces, promoting ocular hydration, promoting corneal hydration, promoting mucus clearance in mucosal surfaces, treatment of ventilator-induced pneumonia, treating chronic bronchitis, treating cystic fibrosis, treating sinusitis, treating vaginal dryness, treating dry eye, treating Sjogren's disease, treating distal intestinal obstruction syndrome, treating dry skin, treating esophagitis, treating dry mouth (xerostomia), treating nasal dehydration, treating chronic obstructive pulmonary disease, treating emphysema, treating pneumonia, treating constipation, treating chronic diverticulitis, treating rhinosinusitis, treating asthma, treating primary ciliary diskinesia, and treating otitis media, comprising administering to a subject an effective amount of a compound represented by formula (I):

• wherein
• X is hydrogen, halogen, trifluoromethyl, (C1-C8) alkyl, unsubstituted or halo-substituted phenyl, (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) alkyl-thio, halogen, (C1-C8) alkyl, unsubstituted or halo-substituted mononuclear aryl, 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)n—C(═O)NR7R10, —(CH2)n—Zg—R7, —(CH2)m—NR10—CH2(CHOR8)(CHOR8)n—CH2OR8, —(CH2)n—CO2R7, or
• R3 and R4 are each, independently, hydrogen, a group represented by formula (A), (C1-C8) alkyl, hydroxy (C1-C8) alkyl, phenyl, phenyl-(C1-C8) alkyl, (halophenyl)-(C1-C8) alkyl, (C1-C8)-(alkylphenylalkyl), (C1-C8) (alkoxyphenyl)-(C1-C8) alkyl, naphthyl-(C1-C8) alkyl, or pyridyl-(C1-C8) alkyl, with the proviso that at least one of R3 and R4 is a group represented by formula (A):
• wherein
• each RL is, independently, —R7, —(CH2)n—OR8, —O—(C2)m—OR8, —(CH2)n—NR7R7R10, —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)n—C(═O)NR7R10, —O—(CH2)m—C(═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,
• each o 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 contiguous chain is from 1 to 10;
• each x is, independently, O, NR10, C(═O), CHOH, C(═N—R10), CHNR7R10, or represents a single bond;
• each 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)n—C(═O)NR7R10, —O—(CH2)m—C(═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,
• each R6 is, independently, —R7, —OR128, —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)n—C(═O)NR7R10, —O—(CH2)m—C(═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), —CO2R7, —O—(CH2)m—CO2R7, —OSO3H, —O-glucuronide, —O-glucose,
• wherein when two R6 are —OR128 and are located adjacent to each other on a phenyl ring, the alkyl moieties of the two R6 may be bonded together to form a methylenedioxy group;
• each R7 is, independently, hydrogen or (C1-C8) alkyl;
• each R8 is, independently, hydrogen, (C1-C8) alkyl, —C(═O)—R128, 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, independently, C—R5 or C—R6, or a nitrogen atom, wherein one Q is a nitrogen atom;
• or a pharmaceutically acceptable salt thereof, and
• inclusive of all enantiomers, diastereomers, and racemic mixtures thereof.