Details for Patent: 9,353,103

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 (Goteborg, SE), Samuelsson; Bengt Bertil (Skarholmen, SE), Rosenquist; Asa Annica Kristina (Huddinge, SE), Ivanov; Vladimir (Moscow, RU), Pelcman; Mikael (Alvsjo, SE), Belfrage; Anna Karin Gertrud Linea (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)
Filing Date:	Apr 13, 2015
Application Number:	14/684,649
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; and another anti-HCV agent. 2. The method of claim 1, comprising administering a pharmaceutically acceptable salt of the compound. 3. The method of claim 2, wherein the pharmaceutically acceptable salt is the sodium salt. 4. The method of claim 1, 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. 5. The method of claim 1, wherein the other anti-HCV agent is an HCV polymerase inhibitor, an HCV protease inhibitor, an antiviral agent, or a combination thereof. 6. The method of claim 1, wherein the other anti-HCV agent is an HCV polymerase inhibitor. 7. The method of claim 1, wherein the other anti-HCV agent is an HCV protease inhibitor. 8. The method of claim 1, wherein the other anti-HCV agent is an antiviral agent. 9. The method of claim 1, wherein the other anti-HCV agent is ribavirin. 10. The method of claim 1, wherein the other anti-HCV agent is pegylated interferon-.alpha.. 11. The method of claim 1, wherein the other anti-HCV agent is ribavirin and pegylated interferon-.alpha.. 12. The method of claim 1, wherein the compound and the other anti-HCV agent are administered simultaneously. 13. The method of claim 1, wherein the compound and the other anti-HCV agent are administered separately. 14. The method of claim 1, wherein the compound and the other anti-HCV agent are administered sequentially.