Claims for Patent: 9,623,022

Summary for Patent: 9,623,022

Title:	Macrocyclic inhibitors of hepatitis C virus
Abstract:	Inhibitors of HCV replication of formula (I) ##STR00001## and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R.sup.1 is --OR.sup.7, --NH--SO.sub.2R.sup.8; R.sup.2 is hydrogen, and where X is C or CH, R.sup.2 may also be C.sub.1-6alkyl; R.sup.3 is hydrogen, C.sub.1-6alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl, C.sub.3-7cycloalkyl; R.sup.4 is aryl or Het; n is 3, 4, 5, or 6; R.sup.5 is halo, C.sub.1-6alkyl, hydroxy, C.sub.1-6alkoxy, phenyl, or Het; R.sup.6 is C.sub.1-6alkoxy, or dimethylamino; R.sup.7 is hydrogen; aryl; Het; C.sub.3-7cycloalkyl optionally substituted with C.sub.1-6alkyl; or C.sub.1-6alkyl optionally substituted with C.sub.3-7cycloalkyl, aryl or with Het; R.sup.8 is aryl; Het; C.sub.3-7cycloalkyl optionally substituted with C.sub.1-6alkyl; or C.sub.1-6alkyl optionally substituted with C.sub.3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
Inventor(s):	Simmen; Kenneth Alan (Tervuren, BE), De Kock; Herman Augustinus (Arendonk, BE), Raboisson; Pierre Jean-Marie Bernard (Sterrebeek, BE), Hu; Lili (Mechelen, BE), Tahri; Abdellah (Anderlecht, BE), Surleraux; Dominique Louis Nestor Ghislain (Braine-le-chateau, BE), Nilsson; Karl Magnus (Gothenburg, SE), Samuelsson; Bengt Bertil (Skarholmen, SE), Rosenquist; .ANG.sa Annica Kristina (Huddinge, SE), Ivanov; Vladimir (Moscow, RU), Pelcman; Mikael (Alvsjo, SE), Belfrage; Anna Karin (Uppsala, SE), Johansson; Per-Ola Mikael (Huddinge, SE), Vendeville; Sandrine Marie Helene (Etterbeek, BE)
Assignee:	Janssen Sciences Ireland UC (Little Island, Co. Cork, IE) Medivir AB (Huddinge, SE)
Application Number:	15/137,997
Patent Claims:	1. A method of treating a hepatitis C virus (HCV) infection in a patient comprising administering to the patient a compound having the formula ##STR00194## or a pharmaceutically acceptable salt thereof. 2. The method of claim 1, wherein the compound is a sodium salt of ##STR00195## 3. The method of claim 1, wherein the patient is infected with HCV genotype 1. 4. The method of claim 3, wherein the compound is administered with another anti-HCV agent. 5. The method of claim 4, wherein the other anti-HCV agent is an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, and immunomodulatory agent, an antiviral agent, or a combination thereof. 6. The method of claim 4, wherein the other anti-HCV agent is an HCV polymerase inhibitor, an HCV protease inhibitor, an antiviral agent, or a combination thereof. 7. The method of claim 4, wherein the other anti-HCV agent is an HCV polymerase inhibitor. 8. The method of claim 4, wherein the other anti-HCV agent is an HCV protease inhibitor. 9. The method of claim 4, wherein the other anti-HCV agent is an antiviral agent. 10. The method of claim 4, wherein the other anti-HCV agent is ribavirin. 11. The method of claim 4, wherein the other anti-HCV agent is pegylated interferon-.alpha.. 12. The method of claim 4, wherein the other anti-HCV agent is ribavirin and pegylated interferon-.alpha.. 13. The method of claim 4, wherein the compound is a sodium salt of ##STR00196## and the other anti-HCV agent is ribavirin and pegylated interferon-a. 14. The method of claim 4, wherein the compound and the other anti-HCV agent are administered simultaneously. 15. The method of claim 4, wherein the compound and the other anti-HCV agent are administered separately. 16. The method of claim 4, wherein the compound and the other anti-HCV agent are administered sequentially.