3,5-diamino-6-chloro-n-(n-(4-phenylbutyl)carbamimidoyl) pyrazine-2- carboxamide compounds

A method for treating reversible or irreversible airway obstruction, chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, including bronchiectasis due to conditions other than cystic fibrosis, acute bronchitis, chronic bronchitis, post-viral cough, cystic fibrosis, emphysema, pneumonia, panbronchiolitis, transplant-associate bronchiolitis, or ventilator-associated tracheobronchitis in a human in need thereof, or for preventing ventilator-associated pneumonia in a human in need thereof, said method comprising administering to said human a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is a moiety selected from the group of:
• X is selected from —CH2—, —O—, and —S—;
• R1 and R2 are independently selected from H and C1-C6 alkyl;
• or R1 and R2 together with the nitrogen atom to which they are bound form a 5-membered or 6-membered heterocyclic ring optionally containing one additional ring heteroatom selected from N and O;
• R3 is an alkyl group having from 3 to 8 carbon atoms or a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• R4 is a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• and
• R5 is selected from H and C1-C3 alkyl;
• or comprising administering to said human a compound of one of the following formulae:
• or a pharmaceutically acceptable salt thereof.

A method for treating dry mouth (xerostomia), dry skin, vaginal dryness, sinusitis, rhinosinusitis, nasal dehydration, including nasal dehydration brought on by administering dry oxygen, dry eye, Sjogren's disease, otitis media, primary ciliary dyskinesia, distal intestinal obstruction syndrome, esophagitis, constipation, or chronic diverticulitis in a human in need thereof, or for promoting ocular or corneal hydration in a human in need thereof, said method comprising administering to said human a compound of the following formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is a moiety selected from the group of:
• X is selected from —CH2—, —O—, and —S—;
• R1 and R2 are independently selected from H and C1-C6 alkyl;
• or R1 and R2 together with the nitrogen atom to which they are bound form a 5-membered or 6-membered heterocyclic ring optionally containing one additional ring heteroatom selected from N and O;
• R3 is an alkyl group having from 3 to 8 carbon atoms or a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• R4 is a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• and
• R5 is selected from H and C1-C3 alkyl;
• or comprising administering to said human a compound of one of the following formulae:
• and pharmaceutically acceptable salts thereof.

A method for blocking sodium channels with compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is a moiety selected from the group of:
• X is selected from —CH2—, —O—, and —S—;
• R1 and R2 are independently selected from H and C1-C6 alkyl;
• or R1 and R2 together with the nitrogen atom to which they are bound form a 5-membered or 6-membered heterocyclic ring optionally containing one additional ring heteroatom selected from N and O;
• R3 is an alkyl group having from 3 to 8 carbon atoms or a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• R4 is a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• and
• R5 is selected from H and C1-C3 alkyl;
• or a compound of one of the following formulae:
• and pharmaceutically acceptable salts thereof.

A method for promoting hydration of mucosal surfaces, improving mucociliary clearance, or restoring mucosal defense in a human comprising administering to said human a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is a moiety selected from the group of:
• X is selected from —CH2—, —O—, and —S—;
• R1 and R2 are independently selected from H and C1-C6 alkyl;
• or R1 and R2 together with the nitrogen atom to which they are bound form a 5-membered or 6-membered heterocyclic ring optionally containing one additional ring heteroatom selected from N and O;
• R3 is an alkyl group having from 3 to 8 carbon atoms or a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• R4 is a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• and
• R5 is selected from H and C1-C3 alkyl;
• or a compound of one of the following formulae:
• and pharmaceutically acceptable salts thereof.

A method for preventing, mitigating, and/or treating deterministic health effects to the respiratory tract and/or other bodily organs caused by respirable aerosols containing radionuclides in a human in need thereof, said method comprising administering to said human a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is a moiety selected from the group of:
• X is selected from —CH2—, —O—, and —S—;
• R1 and R2 are independently selected from H and C1-C6 alkyl;
• or R1 and R2 together with the nitrogen atom to which they are bound form a 5-membered or 6-membered heterocyclic ring optionally containing one additional ring heteroatom selected from N and O;
• R3 is an alkyl group having from 3 to 8 carbon atoms or a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• R4 is a polyhydroxylated alkyl group having from 3 to 8 carbon atoms;
• and
• R5 is selected from H and C1-C3 alkyl;
• or a compound of one of the following formulae:
• and pharmaceutically acceptable salts thereof.