Claims for Patent: 9,732,092

Summary for Patent: 9,732,092

Title:	Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1',2':4,5]pyrazino[2,1-b][1,3]OXAZEPIN- ES and methods for treating viral infections
Abstract:	Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): ##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, X, W, Y.sup.1, Y.sup.2, Z.sup.1, and Z.sup.4 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Inventor(s):	Jin; Haolun (Foster City, CA), Lazerwith; Scott E. (Burlingame, CA), Pyun; Hyung-Jung (Fremont, CA), Bacon; Elizabeth M. (Burlingame, CA), Morganelli; Philip Anthony (Oakland, CA), Ji; Mingzhe (Union City, CA)
Assignee:	Gilead Sciences, Inc. (Foster City, CA)
Application Number:	15/349,934
Patent Claims:	1. A compound having Formula (I): ##STR00140## or a stereoisomer or pharmaceutically acceptable salt thereof, wherein: X is --O--; W is --CHZ.sup.2--; Z.sup.1 and Z.sup.2, taken together, form -L- wherein L is --C(R.sup.a).sub.2C(R.sup.a).sub.2--; Z.sup.4 is --CH.sub.2--; Y.sup.1 and Y.sup.2 are each independently hydrogen, C.sub.1-3alkyl or C.sub.1-3haloalkyl; R.sup.1 is phenyl substituted with one, two or three halogens; and each R.sup.a is independently hydrogen, halo, hydroxy or C.sub.1-4alkyl. 2. The compound of claim 1, wherein R.sup.1 is substituted with one halogen. 3. The compound of claim 2, wherein R.sup.1 is 4-fluorophenyl or 2-fluorophenyl. 4. The compound of claim 1, wherein R.sup.1 is substituted with two halogens. 5. The compound of claim 4, wherein R.sup.1 is 2,4-difluorophenyl, 2,3-difluorophenyl, 2,6-difluorophenyl, 3-fluoro-4-chlorophenyl, 3,4-difluorophenyl, 2-fluoro-4-chlorophenyl, or 3,5-difluorophenyl. 6. The compound of claim 5, wherein R.sup.1 is 2,4-difluorophenyl. 7. The compound of claim 1, wherein R.sup.1 is substituted with three halogens. 8. The compound of claim 7, wherein R.sup.1 is 2,4,6-trifluorophenyl or 2,3,4-trifluorophenyl. 9. The compound of claim 8, wherein R.sup.1 is 2,4,6-trifluorophenyl. 10. The compound of claim 1, wherein Y.sup.1 and Y.sup.2 are each independently hydrogen, methyl or trifluoromethyl. 11. The compound of claim 1, having Formula (II-A): ##STR00141## 12. The compound of claim 1, wherein the compound is selected from the group consisting of: ##STR00142## ##STR00143## ##STR00144## ##STR00145## 13. A pharmaceutical composition comprising a compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 14. RAE pharmaceutical composition of claim 13, further comprising one or more additional therapeutic agents. 15. The pharmaceutical composition of claim 14, wherein the one or more one additional therapeutic agents is an anti-human immunodeficiency virus agent. 16. The pharmaceutical composition of claim 15, wherein the one or more additional therapeutic agents is selected from the group consisting of a human immunodeficiency virus protease inhibitor, a human immunodeficiency virus non-nucleoside inhibitor of reverse transcriptase, a human immunodeficiency virus nucleoside inhibitor of reverse transcriptase and a human immunodeficiency virus nucleotide inhibitor of reverse transcriptase, or a combination thereof.