Details for Patent: 8,741,926

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; .ANG.sa Annica Kristina (Huddinge, SE), Ivanov; Vladimir (Moscow, RU), Pelcman; Mikael (Alvsjo, SE), Belfrage; Anna Karin Gertrud Linnea (Uppsala, SE), Johansson; Per-Ola Mikael (Huddinge, SE), Vendeville; Sandrine Marie Helene (Etterbeek, BE)
Assignee:	Janssen R&D Ireland (Little Island, County Cork, IE) Medivir AB (Huddinge, SE)
Filing Date:	Nov 28, 2012
Application Number:	13/687,037
Claims:	1. A combination comprising: (a) a compound having the formula ##STR00196## or an N-oxide, a pharmaceutically acceptable salt, or stereoisomer thereof; and (b) another anti-HCV compound. 2. The combination according to claim 1 other than an N-oxide or pharmaceutically acceptable salt. 3. The combination according to claim 1 other than an N-oxide. 4. The combination as claimed in claim 1, wherein the other anti-HCV compound is an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, an immunomodulatory agent, an antiviral agent, or combinations thereof. 5. The combination as claimed in claim 4, wherein the other anti-HCV compound is an HCV polymerase inhibitor. 6. The combination as claimed in claim 4, for simultaneous, separate, or sequential use in the treatment of HCV infections. 7. The combination as claimed in claim 5, for simultaneous, separate, or sequential use in the treatment of HCV infections. 8. A method of inhibiting HCV replication comprising administering to a patient in need thereof, a compound of the formula ##STR00197## in combination with another compound. 9. The method as claimed in claim 8, wherein the other compound is another anti-HCV compound. 10. The method as claimed in claim 9, wherein the other anti-HCV compound is an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, an immunomodulatory agent, an antiviral agent, or combinations thereof. 11. The method as claimed in claim 9, wherein the other anti-HCV compound is an HCV polymerase inhibitor. 12. The method as claimed in claim 10, wherein the combination is administered simultaneously, separately, or sequentially in the treatment of the HCV replication inhibition. 13. The method as claimed in claim 11, wherein the combination is administered simultaneously, separately, or sequentially in the treatment of the HCV replication inhibition. 14. A pharmaceutical composition comprising a carrier, and as active ingredient an anti-virally effective amount of a combination comprising (a) a compound having the formula ##STR00198## or an N-oxide, a pharmaceutically acceptable salt, or stereoisomer thereof; and (b) another anti-HCV compound. 15. The pharmaceutical composition of claim 14 wherein the other anti-HCV compound is an HCV polymerase inhibitor, an HCV protease inhibitor, an inhibitor of another target in the HCV life cycle, an immunomodulatory agent, an antiviral agent, or combinations thereof. 16. The pharmaceutical composition of claim 14 wherein the other anti-HCV compound is an HCV polymerase inhibitor. 17. The combination of claim 4, wherein the other anti-HCV compound is a protease inhibitor. 18. The method of claim 8, wherein the other compound is a protease inhibitor. 19. The pharmaceutical composition of claim 14, wherein the other anti-HCV compound is a protease inhibitor.