Ombitasvir heminonahydrateProduct ingredient for Ombitasvir

Name
Ombitasvir heminonahydrate
Drug Entry
Ombitasvir

Ombitasvir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 8. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Ombitasvir. Ombitasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly Label. The barrier for develoment of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs 5.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Ombitasvir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4 8. Depending on the genotype, Ombitasvir is often used in combination with other antivirals such as Dasabuvir, Paritaprevir, Ritonavir, and Ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 6. Treatment with direct acting antivirals such as Ombitasvir is associated with very minimal side effects, with the most common being headache and fatigue Label. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects 7.

Ombutasvir first came on the market as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

Ombutasvir is also available as a fixed-dose combination product with Paritaprevir and Ritonavir as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

In Canada, Ombutasvir is also available as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.

Accession Number
DBSALT002724
Structure
Thumb
Synonyms
Not Available
UNII
EQE3I70J3W
CAS Number
1456607-70-7
Weight
Average: 1950.389
Monoisotopic: 1949.10530645
Chemical Formula
C100H152N14O25
InChI Key
AWMWWEBJJCSJHI-MVJJBPFMSA-N
InChI
InChI=1S/2C50H67N7O8.9H2O/c2*1-30(2)42(53-48(62)64-8)46(60)55-28-10-12-40(55)44(58)51-35-20-14-32(15-21-35)38-26-27-39(57(38)37-24-18-34(19-25-37)50(5,6)7)33-16-22-36(23-17-33)52-45(59)41-13-11-29-56(41)47(61)43(31(3)4)54-49(63)65-9;;;;;;;;;/h2*14-25,30-31,38-43H,10-13,26-29H2,1-9H3,(H,51,58)(H,52,59)(H,53,62)(H,54,63);9*1H2/t2*38-,39-,40-,41-,42-,43-;;;;;;;;;/m00........./s1
IUPAC Name
bis(methyl N-[(2S)-1-[(2S)-2-({4-[(2S,5S)-1-(4-tert-butylphenyl)-5-{4-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidine-2-amido]phenyl}pyrrolidin-2-yl]phenyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate) nonahydrate
SMILES
O.O.O.O.O.O.O.O.O.[H]N([C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C(C=C1)[C@@H]1CC[C@H](N1C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)N([H])C(=O)[C@@H]1CCCN1C(=O)[C@@H](N([H])C(=O)OC)C(C)C)C(=O)OC.[H]N([C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C(C=C1)[C@@H]1CC[C@H](N1C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)N([H])C(=O)[C@@H]1CCCN1C(=O)[C@@H](N([H])C(=O)OC)C(C)C)C(=O)OC
External Links
ChemSpider
34990329
Predicted Properties
PropertyValueSource
Water Solubility0.00193 mg/mLALOGPS
logP5.6ALOGPS
logP7.49ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)12.77ChemAxon
pKa (Strongest Basic)2.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area178.72 Å2ChemAxon
Rotatable Bond Count32ChemAxon
Refractivity250.79 m3·mol-1ChemAxon
Polarizability98.92 Å3ChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon