Disclosed are guanidinyl pyrazine compounds of formula (I) and methods of their preparation. Specific examples of compounds of formula (I) include: 3,5-Diamino-6-chloro-N-(N-{ 4-[6-(2,3-dihydropropoxy)naphthalen-2-yl]butyl} carbamimidoyl)pyrazine-2-carboxamide, 3,5-Diamino-6-chloro-N-(N-{ 4-[6-(2,3-dihydropropoxy)naphthalen-2-yl]butyl} carbamimidoyl)pyrazine-2-carboxamide, 3,5-Diamino-N-(N-{ 4-[4-(3-aminopropoxy)naphthalen-1-yl]butyl} carbamimidoyl)-6-chloropyrazine-2-carboxamide, and 3,5-Diamino-N-(N-{ 4-[6-(3-aminopropoxy)naphthalen-2-yl]butyl} carbamimidoyl-6-chloropyrazine-2-carboxamide. Compounds of formula (I) are useful for promoting hydration of a mucosal surface, and for treating anthrax, plague, chronic bronchitis, treating bronchiectasis, treating cystic fibrosis, treating sinusitis, treating vaginal dryness, treating dry eye, promoting ocular hydration, promoting corneal hydration, promoting mucus clearance in mucosal surfaces, treating Sjogrens disease, treating distal intestinal obstruction syndrome, treating dry skin, treating esophagitis, treating dry mouth, treating nasal dehydration, treating ventilator-induced pneumonia, treating asthma, treating primary ciliary dyskinesia, treating otitis media, inducing sputum for diagnostic purposes, treating chronic obstructive pulmonary disease, treating emphysema, treating pneumonia, treating constipation, treating chronic diverticulitis, treating rhinosinusitis, treating hypertension, reducing blood pressure, treating edema, promoting diuresis, promoting natriuresis, and/or promoting saluresis. The compounds of formula (I) can be used in combination with an osmolyte for treating a disease ameliorated by increased mucociliary clearance or mucosal hydration or for inducing sputum.
