Claims for Patent: 8,183,252

Summary for Patent: 8,183,252

Title:	Heterocyclic aspartyl protease inhibitors
Abstract:	Disclosed are compounds of the formula I ##STR00001## or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, --C(.dbd.S)--, --S(O)--, --S(O).sub.2--, --C(.dbd.O)--, --O--, --C(R.sup.6)(R.sup.7)--, --N(R.sup.5)-- or --C(.dbd.N(R.sup.5))--; X is --O--, --N(R.sup.5)-- or --C(R.sup.6)(R.sup.7)--; provided that when X is --O--, U is not --O--, --S(O)--, --S(O).sub.2--, --C(.dbd.O)-- or --C(.dbd.NR.sup.5)--; U is a bond, --S(O)--, --S(O).sub.2--, --C(O)--, --O--, --P(O)(OR.sup.15)--, --C(.dbd.NR.sup.5)--, --(C(R.sup.6)(R.sup.7)).sub.b-- or --N(R.sup.5)--; wherein b is 1 or 2; provided that when W is --S(O)--, --S(O).sub.2--, --O--, or --N(R.sup.5)--, U is not --S(O)--, --S(O).sub.2--, --O--, or --N(R.sup.5)--; provided that when X is --N(R.sup.5)-- and W is --S(O)--, --S(O).sub.2--, --O--, or --N(R.sup.5)--, then U is not a bond; and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m.sub.1 agonist or m.sub.2 antagonist.
Inventor(s):	Zhu; Zhaoning (Plainsboro, NJ), Sun; Zhong-Yue (Parlin, NJ), Stamford; Andrew (Chatham Township, NJ), Greenlee; William J. (Teaneck, NJ), Cumming; Jared N. (Garwood, NJ), Wang; Lingyan (East Brunswick, NJ), Iserloh; Ulrich (Hoboken, NJ), Liu; Xiaoxiang (River Vale, NJ), Huang; Ying (Berkeley Heights, NJ), Li; Guoqing (Belle Mead, NJ), Pan; Jianping (Monmouth Junction, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ) Pharmacopeia Inc. (La Jolla, CA)
Application Number:	12/693,874
Patent Claims:	1. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is selected from the group consisting of: TABLE-US-00063 Str # Structure 1928 ##STR04550## 1945 ##STR04551## 1990 ##STR04552## 2055 ##STR04553## 2089 ##STR04554## 2106 ##STR04555## 2107 ##STR04556## 2118 ##STR04557## 2130 ##STR04558## 2131 ##STR04559## 2174 ##STR04560## 2178 ##STR04561## 2190 ##STR04562## 2196 ##STR04563## 2218 ##STR04564## 2219 ##STR04565## 2230 ##STR04566## 2253 ##STR04567## 2267 ##STR04568## 2314 ##STR04569## 2330 ##STR04570## 2340 ##STR04571## 2341 ##STR04572## 2357 ##STR04573## 2388 ##STR04574## 2438 ##STR04575## 2444 ##STR04576## 2455 ##STR04577## 2459 ##STR04578## 2470 ##STR04579## 2479 ##STR04580## 2489 ##STR04581## 2516 ##STR04582## 2522 ##STR04583## 2561 ##STR04584## 2562 ##STR04585## 2588 ##STR04586## 2598 ##STR04587## 2723 ##STR04588## 2733 ##STR04589## 2739 ##STR04590## 2759 ##STR04591## 2782 ##STR04592## 2801 ##STR04593## 2811 ##STR04594## 2833 ##STR04595## 2867 ##STR04596## 2870 ##STR04597## 2937 ##STR04598## 2983 ##STR04599## 3042 ##STR04600## 3044 ##STR04601## 3054 ##STR04602## 3104 ##STR04603## 3108 ##STR04604## 3112 ##STR04605## 3126 ##STR04606## 3149 ##STR04607## 3182 ##STR04608## 3189 ##STR04609## 3206 ##STR04610## 3241 ##STR04611## 3243 ##STR04612## 3251 ##STR04613## 3256 ##STR04614## 3259 ##STR04615## 3275 ##STR04616## 3306 ##STR04617## 3346 ##STR04618## 3368 ##STR04619## 3383 ##STR04620## 3411 ##STR04621## 3422 ##STR04622## 3426 ##STR04623## 3435 ##STR04624## 3540 ##STR04625## 3630 ##STR04626## 3659 ##STR04627## 3680 ##STR04628## 3735 ##STR04629## 3745 ##STR04630## 3763 ##STR04631## 3783 ##STR04632## 3873 ##STR04633## 3884 ##STR04634## 3888 ##STR04635## 3939 ##STR04636## 3963 ##STR04637## 3986 ##STR04638## 4018 ##STR04639## 4069 ##STR04640## 4070 ##STR04641## 4088 ##STR04642## 4098 ##STR04643## 4105 ##STR04644## 4115 ##STR04645## 4160 ##STR04646## 4165 ##STR04647## 4177 ##STR04648## 4207 ##STR04649## 4222 ##STR04650## 4257 ##STR04651## 4262 ##STR04652## 4284 ##STR04653## 4287 ##STR04654## 4290 ##STR04655## 4295 ##STR04656## 4308 ##STR04657## 4313 ##STR04658## 4318 ##STR04659## 4327 ##STR04660## 4328 ##STR04661## ##STR04662## ##STR04663## ##STR04664## ##STR04665## ##STR04666## ##STR04667## ##STR04668## ##STR04669## ##STR04670## ##STR04671## ##STR04672## ##STR04673## ##STR04674## ##STR04675## ##STR04676## ##STR04677## ##STR04678## ##STR04679## ##STR04680## ##STR04681## ##STR04682## ##STR04683## ##STR04684## ##STR04685## ##STR04686## ##STR04687## ##STR04688## ##STR04689## ##STR04690## ##STR04691## ##STR04692## ##STR04693## ##STR04694## ##STR04695## ##STR04696## ##STR04697## ##STR04698## ##STR04699## ##STR04700## ##STR04701## ##STR04702## ##STR04703## ##STR04704## ##STR04705## ##STR04706## ##STR04707## ##STR04708## ##STR04709## ##STR04710## ##STR04711## ##STR04712## ##STR04713## ##STR04714## ##STR04715## ##STR04716## ##STR04717## ##STR04718## ##STR04719## ##STR04720## ##STR04721## ##STR04722## ##STR04723## ##STR04724## ##STR04725## ##STR04726## ##STR04727## ##STR04728## ##STR04729## ##STR04730## ##STR04731## ##STR04732## ##STR04733## ##STR04734## ##STR04735## ##STR04736## ##STR04737## ##STR04738## ##STR04739## ##STR04740## ##STR04741## ##STR04742## ##STR04743## ##STR04744## ##STR04745## ##STR04746## ##STR04747## ##STR04748## ##STR04749## ##STR04750## 2. A pharmaceutically acceptable salt of a compound, or a tautomer thereof, according to claim 1, wherein said salt is selected from: acetate, adipate, alginate, ascorbate, aspartate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, and hexanoate. 3. A pharmaceutically acceptable salt of a compound, or a tautomer thereof, according to claim 1, wherein said salt is selected from: hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonates, tartarate, thiocyanate, tosylate, and undecanoate. 4. A pharmaceutically acceptable salt of claim 1, wherein said salt is the tosylate salt. 5. A pharmaceutical composition comprising a compound of claim 1, or said tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 6. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is selected from the group consisting of: TABLE-US-00064 Str # Structure ##STR04751## 2106 ##STR04752## 2782 ##STR04753## 3306 ##STR04754## 3383 ##STR04755## 3659 ##STR04756## 3783 ##STR04757## 3884 ##STR04758## 3963 ##STR04759## 3986 ##STR04760## 4308 ##STR04761## 4327 ##STR04762## 1945 ##STR04763## 2118 ##STR04764## 2130 ##STR04765## 2174 ##STR04766## 2178 ##STR04767## 2388 ##STR04768## 2438 ##STR04769## 2723 ##STR04770## 2759 ##STR04771## 2833 ##STR04772## 2937 ##STR04773## 2983 ##STR04774## 3368 ##STR04775## 4069 ##STR04776## 4088 ##STR04777## 4115 ##STR04778## 4165 ##STR04779## 4177 ##STR04780## 4328 ##STR04781## 7. A pharmaceutically acceptable salt of a compound, or a tautomer thereof, according to claim 6, wherein said salt is selected from: acetate, adipate, alginate, ascorbate, aspartate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, and hexanoate. 8. A pharmaceutically acceptable salt of a compound, or a tautomer thereof, according to claim 6, wherein said salt is selected from: hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonates, tartarate, thiocyanate, tosylate, and undecanoate. 9. A pharmaceutically acceptable salt of a compound, or a tautomer thereof, according to claim 6, wherein said salt is the tosylate salt. 10. A pharmaceutical composition comprising a compound of claim 6, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 11. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00065 Str # Structure 2106 ##STR04782## 12. A pharmaceutically acceptable salt of said compound of claim 11, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 13. A pharmaceutical composition comprising a compound of claim 11, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 14. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, vvherein said compound is: TABLE-US-00066 Structure ##STR04783## 15. A pharmaceutically acceptable salt of said compound of claim 14, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 16. A pharmaceutical composition comprising a compound of claim 14, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 17. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer wherein said compound is: TABLE-US-00067 Str # Structure 4327 ##STR04784## 18. A pharmaceutically acceptable salt of said compound of claim 17, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 19. A pharmaceutical composition comprising a compound of claim 17, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 20. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00068 Structure ##STR04785## 21. A pharmaceutically acceptable salt of said compound of claim 20, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 22. A pharmaceutical composition comprising a compound of claim 20, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 23. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00069 Str # Structure 2782 ##STR04786## 24. A pharmaceutically acceptable salt of said compound of claim 23, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 25. A pharmaceutical composition comprising a compound of claim 23, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 26. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00070 Structure ##STR04787## 27. A pharmaceutically acceptable salt of said compound of claim 26, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 28. A pharmaceutical composition comprising a compound of claim 26, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 29. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer wherein said compound is selected from: TABLE-US-00071 Str # Structure 3306 ##STR04788## 30. A pharmaceutically acceptable salt of said compound of claim 29, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 31. A pharmaceutical composition comprising a compound of claim 29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 32. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is selected from: TABLE-US-00072 Str # Structure 4207 ##STR04789## 33. A pharmaceutically acceptable salt of said compound of claim 32, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 34. A pharmaceutical composition comprising a compound of claim 32, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 35. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00073 Str # Structure 3383 ##STR04790## 36. A pharmaceutically acceptable salt of said compound of claim 35, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 37. A pharmaceutical composition comprising a compound of claim 35, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 38. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00074 Structure ##STR04791## 39. A pharmaceutically acceptable salt of said compound of claim 38, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 40. A pharmaceutical composition comprising a compound of claim 38, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 41. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00075 Str # Structure 3659 ##STR04792## 42. A pharmaceutically acceptable salt of said compound of claim 41, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 43. A pharmaceutical composition comprising a compound of claim 41, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 44. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00076 Structure ##STR04793## 45. A pharmaceutically acceptable salt of said compound of claim 44, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 46. A pharmaceutical composition comprising a compound of claim 44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 47. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00077 Str # Structure 3783 ##STR04794## 48. A pharmaceutically acceptable salt of said compound of claim 47, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 49. A pharmaceutical composition comprising a compound of claim 47, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 50. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00078 Structure ##STR04795## 51. A pharmaceutically acceptable salt of said compound of claim 50, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 52. A pharmaceutical composition comprising a compound of claim 50, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 53. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00079 Str # Structure 3884 ##STR04796## 54. A pharmaceutically acceptable salt of said compound of claim 53, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 55. A pharmaceutical composition comprising a compound of claim 53, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 56. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00080 Structure ##STR04797## 57. A pharmaceutically acceptable salt of said compound of claim 56, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 58. A pharmaceutical composition comprising a compound of claim 56, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 59. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00081 Str # Structure 3963 ##STR04798## 60. A pharmaceutically acceptable salt of said compound of claim 59, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 61. A pharmaceutical composition comprising a compound of claim 59, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 62. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00082 Structure ##STR04799## 63. A pharmaceutically acceptable salt of said compound of claim 62, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 64. A pharmaceutical composition comprising a compound of claim 62, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 65. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00083 Str # Structure 3986 ##STR04800## 66. A pharmaceutically acceptable salt of said compound of claim 65, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 67. A pharmaceutical composition comprising a compound of claim 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 68. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00084 Structure ##STR04801## 69. A pharmaceutically acceptable salt of said compound of claim 68, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 70. A pharmaceutical composition comprising a compound of claim 68, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 71. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is: TABLE-US-00085 Str # Structure 4308 ##STR04802## 72. A pharmaceutically acceptable salt of said compound of claim 71, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 73. A pharmaceutical composition comprising a compound of claim 71, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 74. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said comnound or said tautomer, wherein said compound is: TABLE-US-00086 Structure ##STR04803## 75. A pharmaceutically acceptable salt of said compound of claim 74, or said tautomer thereof, wherein said salt of said compound or said tautomer is the tosylate salt. 76. A pharmaceutical composition comprising a compound of claim 74, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable carrier. 77. A pharmaceutical composition according to any one of claims 5, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, or 76, further comprising at least one additional active agent selected from: a cholinesterase inhibitor; a muscarinic m.sub.1 agonist; a muscarinic m.sub.2 antagonist; a N-methyl-D-aspartate receptor antagonist; a beta secretase inhibitor other than a compound of claim 1; a gamma secretase inhibitor; an HMG-CoA reductase inhibitor; a cholesterol absorption inhibitor; a non-steroidal anti-inflammatory agent; an anti-amyloid antibody; vitamin E; a nicotinic acetylcholine receptor agonist; a CB1 receptor inverse agonist; a CB1 receptor antagonist; an antibiotic; a growth hormone secretagogue; a histamine H3 antagonist; an AMPA agonist; a PDE4 inhibitor; a GABA.sub.A inverse agonist; an inhibitor of amyloid aggregation; a glycogen synthase kinase beta inhibitor; and a promoter of alpha secretase activity; and a pharmaceutically acceptable carrier. 78. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is a cholinesterase inhibitor selected from tacrine, donepezil, rivastigmine, galantamine, pyridostigmine and neostig mine. 79. A pharmaceutical composition of claim 78, wherein said cholinesterase inhibitor is selected from tacrine, donepezil, rivastigmine and galantamine. 80. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is a muscarinic m.sub.1 agonist and a muscarinic m.sub.2 antagonist. 81. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is an N-methyl-D-aspartate receptor antagonist. 82. A pharmaceutical composition of claim 81, wherein said N-methyl-D-aspartate receptor antagonist is memantine. 83. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is a gamma secretase inhibitor. 84. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is at least one agent selected from an HMG-CoA reductase inhibitor and a cholesterol absorption inhibitor. 85. A pharmaceutical composition of claim 84, wherein said HMG-CoA reductase inhibitor selected from atorvastatin, lovastatin, simvistatin, pravastatin, fluvastatin and rosuvastatin. 86. A pharmaceutical composition of claim 84, wherein said at least one additional active agent is ezetimibe. 87. A pharmaceutical composition of claim 77, wherein said at least one additional active agent is at least one non-steroidal anti-inflammatory agent. 88. A pharmaceutical composition of claim 87, wherein said at least one non-steroidal anti-inflammatory agent is selected from ibuprofen, relafen and naproxen.

Details for Patent 8,183,252

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2027-02-23