Details for Patent: 10,053,474
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Title: | Anti-viral compounds |
Abstract: | The present invention features compounds effective in inhibiting active against Hepatitis C virus ("HCV") polymerase. The invention also features processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection. |
Inventor(s): | Chau; Jaclyn (Vancouver, CA), Chen; Hui-Ju J. (Grayslake, IL), DeGoey; David A. (Salem, WI), Hartung; John (Evanston, IL), Ide; Nathan (Lindenhurst, IL), Kalthod; Vikram (North Chicago, IL), Krueger; Allan C. (Gurnee, IL), Ku; Yi-Yin (Buffalo Grove, IL), Li; Tongmei (Lake Bluff, IL), Randolph; John T. (Libertyville, IL), Wagner; Rolf (Antioch, IL), Halvorsen; Geoff T. (Lake Bluff, IL), Marvin; Christopher C. (Grayslake, IL), Voight; Eric (Pleasant Prairie, WI), Brown; Brian S. (Evanston, IL), Martinez; Steven R. (Chicago, IL), Shrestha; Anurupa (Gurnee, IL), Heyman; Howard R. (Deerfield, IL) |
Assignee: | AbbVie Inc. (North Chicago, IL) |
Filing Date: | May 05, 2017 |
Application Number: | 15/588,037 |
Claims: | 1. A compound of Formula VII'', or a pharmaceutically acceptable salt thereof ##STR00212## wherein, X is selected from the group consisting of O and C.dbd.CH.sub.2; R.sub.1 and R.sub.2 are independently selected from the group consisting of F, Cl, Br, CH.sub.3, CHF.sub.2 and CCH, R.sub.3, R.sub.4 and R.sub.5 are independently selected from the group consisting of H, D, F, N.sub.3, OCH.sub.3, CN, OH, 1H-tetrazol-5-yl, 2H-tetrazol-2-yl, 1H-tetrazol-1-yl, 1H-imidazol-1-yl, 1H-imidazol-2-yl and 1H-imidazol-5-yl; and P.sub.1 is selected from a group consisting of: ##STR00213## ##STR00214## ##STR00215## ##STR00216## ##STR00217## ##STR00218## ##STR00219## 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is Br and R.sub.2 is F or R.sub.1 is Cl and R.sub.2 is F. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is Br and R.sub.2 is F. 4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sub.3 is OH and R.sub.4 is H. 5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sub.3 is OH. 6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is O. 7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sub.5 is selected from a group consisting of H, D, F, N.sub.3, OCH.sub.3, CN, OH, 1H-tetrazol-5-yl, 2H-tetrazol-2-yl, 1H-tetrazol-1-yl, 1H-imidazol-1-yl, 1H-imidazol-2-yl and 1H-imidazol-5-yl. 8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from a group consisting of: (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-4-bromo-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o) propanoate, (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-4-bromo-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-y- l)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)propanoateethyl 2-(((R)-(((2R,3R,4S,5R)-4-bromo-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-y- l)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)-2-methylpropanoate, ethyl 2-(((((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-- 3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)-- 2-methylpropanoate, ethyl 2-(((((2R,3R,4R,5R)-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)-- 2-methylpropanoate, ethyl 2-(((((2R,3R,5R)-4,4-dichloro-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)- -3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)-2-methyl- propanoate, and (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-4-bromo-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl) amino)propanoate. 9. The compound of claim 1, where said compound is (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-4-bromo-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-y- l)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)propanoate, or a pharmaceutically acceptable salt thereof. 10. The compound of claim 1, where said compound is Ethyl 2-(((((2R,3R,4R,5R)-4-bromo-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidin-1(- 2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)-2- -methylpropanoate, or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1, where said compound is Ethyl 2-(((R)-(((2R,3R,4R,5R)-4-bromo-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)-2-methylpropanoate, or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, where said compound is Ethyl 2-(((S)-(((2R,3R,4R,5R)-4-bromo-4-chloro-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)-2-methylpropanoate, or a pharmaceutically acceptable salt thereof. 13. The compound of claim 1, where said compound is Ethyl 2-(((S)-(((2R,3R,4S,5R)-4-bromo-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-y- l)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amin- o)-2-methylpropanoate, or a pharmaceutically acceptable salt thereof. 14. A method for treating HCV, comprising administering a compound or salt of claim 1 to a patient infected with Hepatitis C Virus. 15. A method for treating HCV, comprising administering a compound or salt of claim 7 to a patient infected with Hepatitis C Virus. 16. A pharmaceutical composition comprising a compound or salt of claim 1. 17. A pharmaceutical composition comprising a compound or salt of claim 8. |