Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called HCV.  At least six different HCV genotypes (with several subtypes within each genotype) are known to date.  In North America, HCV genotype 1a predominates, followed by HCV genotypes 1b, 2a, 2b, and 3a.  In the United States, HCV genotypes 1, 2, and 3 are the most common, with about 80% of the hepatitis C patients having HCV genotype 1.  In Europe, HCV genotype 1b is predominant, followed by HCV genotypes 2a, 2b, 2c, and 3a.  HCV genotypes 4 and 5 are found almost exclusively in Africa.  As discussed below, the patient's HCV genotype is clinically important in determining the patient's potential response to therapy and the required duration of such therapy. 
An HCV infection can cause liver inflammation (hepatitis) that is often asymptomatic, but ensuing chronic hepatitis can result in cirrhosis of the liver (fibrotic scarring of the liver), liver cancer, and/or liver failure.  The World Health Organization estimates that about 170 million persons worldwide are chronically infected with HCV, and from about three to about four million persons are newly infected globally each year.  According to the Centers for Disease Control and Prevention, about four million people in the United States are infected with HCV.  Co-infection with the human immunodeficiency virus (HIV) is common, and rates of HCV infection among HIV positive populations are higher. 
There is a small chance of clearing the virus spontaneously, but the majority of patients with chronic hepatitis C will not clear it without treatment.  Indications for treatment typically include proven HCV infection and persistent abnormal liver function tests.  There are two treatment regimens that are primarily used to treat hepatitis C: monotherapy (using an interferon agent—either a “conventional” or longer-acting pegylated interferon) and combination therapy (using an interferon agent and ribavirin).  Interferon, which is injected into the bloodstream, works by bolstering the immune response to HCV; and ribavirin, which is taken orally, is believed to work by preventing HCV replication.  Taken alone, ribavirin does not effectively suppress HCV levels, but an interferon/ribavirin combination is more effective than interferon alone.  Typically, hepatitis C is treated with a combination of pegylated interferon alpha and ribavirin for a period of 24 or 48 weeks, depending on the HCV genotype. 
The goal of treatment is sustained viral response—meaning that HCV is not measurable in the blood after therapy is completed.  Current standard of care, including interferon and ribavirin, is known to require as many as 24-48 weeks of treatment to achieve any sustained viral response, and cure rates (sustained viral response) from treatment with standard of care in HCV genotypes 2 and 3 is often insufficient and even less sufficient in those with HCV genotypes 1 and 4. 
Treatment may be physically demanding, particularly for those with prior history of drug or alcohol abuse, because both interferon and ribavirin have numerous side effects.  Common interferon-associated side effects include flu-like symptoms, extreme fatigue, nausea, loss of appetite, thyroid problems, high blood sugar, hair loss, and skin reactions at the injection site.  Possible serious interferon-associated side effects include psychoses (e.g., suicidal behavior), heart problems (e.g., heart attack, low blood pressure), other internal organ damage, blood problems (e.g., blood counts falling dangerously low), and new or worsening autoimmune disease (e.g., rheumatoid arthritis).  Ribavirin-associated side effects include anemia, fatigue, irritability, skin rash, nasal stuffiness, sinusitis, and cough.  Ribavirin can also cause birth defects, so pregnancy in female patients and female partners of male patients must be avoided during treatment and for six months afterward. 
Some patients do not complete treatment because of the serious side effects discussed above; other patients (non-responders) continue to have measurable HCV levels despite treatment; and yet other patients (relapsers) “appear to clear” the virus during therapy, but the virus returns sometime after completion of the treatment regimen.  Thus, there continues to be a need for alternative compounds, compositions, and methods of treatment (used either in combination with or in lieu of an interferon agent and/or ribavirin) to treat hepatitis C. This disclosure provides compounds (including salts thereof), compositions, and methods of treatment that address such a need.