MXPA05006167A

MXPA05006167A - Composiciones de inhibidores de la proteina de transferencia de colesteril ester e inhibidores de la hmg-coa reductasa.

Composiciones de inhibidores de la proteina de transferencia de colesteril ester e inhibidores de la hmg-coa reductasa.

Info

Publication number: MXPA05006167A
Authority: MX; Mexico
Prior art keywords: phenyl; amino; propanol; trifluoro; methyl
Prior art date: 2002-12-20

Application number

MXPA05006167A

Other languages

English (en)

Spanish (es)

Inventor

Mysore Shanker Ravi

Original Assignee

Pfizer Prod Inc

Priority date

2002-12-20

Filing date

2003-12-18

Publication date

2005-08-26

2003-12-18 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2005-08-26 Publication of MXPA05006167A publication Critical patent/MXPA05006167A/es

Links

239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title claims abstract description 153
239000000203 mixture Substances 0.000 title claims abstract description 115
229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 16
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title claims abstract description 16
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 5
239000002156 adsorbate Substances 0.000 claims abstract description 126
239000000758 substrate Substances 0.000 claims abstract description 122
229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims abstract description 98
239000007787 solid Substances 0.000 claims abstract description 96
239000003112 inhibitor Substances 0.000 claims abstract description 43
108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 claims abstract description 37
102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 claims abstract description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 490
-1 isopropyl ester Chemical class 0.000 claims description 369
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 281
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 201
229920000642 polymer Polymers 0.000 claims description 131
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 115
238000000034 method Methods 0.000 claims description 65
150000001875 compounds Chemical class 0.000 claims description 50
238000004090 dissolution Methods 0.000 claims description 34
239000002609 medium Substances 0.000 claims description 28
230000002708 enhancing effect Effects 0.000 claims description 25
238000001727 in vivo Methods 0.000 claims description 14
238000000338 in vitro Methods 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 11
239000002552 dosage form Substances 0.000 claims description 11
210000004369 blood Anatomy 0.000 claims description 10
239000008280 blood Substances 0.000 claims description 10
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 8
230000002378 acidificating effect Effects 0.000 claims description 8
239000012736 aqueous medium Substances 0.000 claims description 7
230000007935 neutral effect Effects 0.000 claims description 7
CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 claims description 7
229950004514 torcetrapib Drugs 0.000 claims description 7
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
229960005370 atorvastatin Drugs 0.000 claims description 6
239000002775 capsule Substances 0.000 claims description 6
239000003826 tablet Substances 0.000 claims description 5
230000006872 improvement Effects 0.000 claims description 4
239000006187 pill Substances 0.000 claims description 4
238000002648 combination therapy Methods 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
FJLGEFLZQAZZCD-JUFISIKESA-N (3S,5R)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@H](O)C[C@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-JUFISIKESA-N 0.000 claims 2
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims 2
AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims 2
AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims 2
BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims 2
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims 2
VDSBXXDKCUBMQC-HNGSOEQISA-N (4r,6s)-6-[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohexen-1-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C1=C(F)C(C)=CC(C=2CC(C)(C)CC(C)(C)C=2\C=C\[C@H]2OC(=O)C[C@H](O)C2)=C1 VDSBXXDKCUBMQC-HNGSOEQISA-N 0.000 claims 1
VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 claims 1
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims 1
TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims 1
RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims 1
VXDSGTRNDFHIJB-QQPOVDNESA-N [(1s,4ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1CCC[C@@H](C21)OC(=O)[C@@H](C)CC)=CC(C)C2CC[C@@H]1C[C@@H](O)CC(=O)O1 VXDSGTRNDFHIJB-QQPOVDNESA-N 0.000 claims 1
229960005110 cerivastatin Drugs 0.000 claims 1
SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims 1
GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims 1
229950003040 dalvastatin Drugs 0.000 claims 1
VXDSGTRNDFHIJB-UHFFFAOYSA-N dihydrocompactin Natural products C12C(OC(=O)C(C)CC)CCCC2C=CC(C)C1CCC1CC(O)CC(=O)O1 VXDSGTRNDFHIJB-UHFFFAOYSA-N 0.000 claims 1
229960003765 fluvastatin Drugs 0.000 claims 1
150000002596 lactones Chemical group 0.000 claims 1
229960004844 lovastatin Drugs 0.000 claims 1
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims 1
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims 1
229950009116 mevastatin Drugs 0.000 claims 1
229960002965 pravastatin Drugs 0.000 claims 1
TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 1
229960000672 rosuvastatin Drugs 0.000 claims 1
BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims 1
229960002855 simvastatin Drugs 0.000 claims 1
239000003814 drug Substances 0.000 description 211
229940079593 drug Drugs 0.000 description 211
125000000217 alkyl group Chemical group 0.000 description 188
125000004432 carbon atom Chemical group C* 0.000 description 182
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 171
125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 description 154
229910052717 sulfur Inorganic materials 0.000 description 131
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 127
125000003545 alkoxy group Chemical group 0.000 description 119
229910052757 nitrogen Inorganic materials 0.000 description 114
125000004043 oxo group Chemical group O=* 0.000 description 110
229920006395 saturated elastomer Polymers 0.000 description 110
229910052799 carbon Inorganic materials 0.000 description 106
125000003118 aryl group Chemical group 0.000 description 95
229910052760 oxygen Inorganic materials 0.000 description 93
229910052739 hydrogen Inorganic materials 0.000 description 90
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 88
239000001257 hydrogen Substances 0.000 description 88
239000011593 sulfur Substances 0.000 description 88
125000005843 halogen group Chemical group 0.000 description 87
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 86
125000001424 substituent group Chemical group 0.000 description 82
229960004592 isopropanol Drugs 0.000 description 79
125000000623 heterocyclic group Chemical group 0.000 description 75
239000001301 oxygen Substances 0.000 description 74
229910052736 halogen Inorganic materials 0.000 description 72
125000005842 heteroatom Chemical group 0.000 description 70
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 69
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 66
150000002431 hydrogen Chemical class 0.000 description 62
239000002904 solvent Substances 0.000 description 62
125000003342 alkenyl group Chemical group 0.000 description 61
125000004093 cyano group Chemical group *C#N 0.000 description 60
125000000753 cycloalkyl group Chemical group 0.000 description 59
150000002367 halogens Chemical class 0.000 description 57
125000004453 alkoxycarbonyl group Chemical group 0.000 description 56
125000004414 alkyl thio group Chemical group 0.000 description 56
GILIYJDBJZWGBG-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-ol Chemical compound CC(O)C(F)(F)F GILIYJDBJZWGBG-UHFFFAOYSA-N 0.000 description 55
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 54
125000001072 heteroaryl group Chemical group 0.000 description 51
239000000243 solution Substances 0.000 description 49
125000006850 spacer group Chemical group 0.000 description 49
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 46
125000006343 heptafluoro propyl group Chemical group 0.000 description 45
125000000876 trifluoromethoxy group Chemical class FC(F)(F)O* 0.000 description 44
125000002252 acyl group Chemical class 0.000 description 42
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 41
125000000304 alkynyl group Chemical group 0.000 description 40
150000003254 radicals Chemical class 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
125000004429 atom Chemical group 0.000 description 28
125000000392 cycloalkenyl group Chemical group 0.000 description 28
125000001188 haloalkyl group Chemical group 0.000 description 28
125000001153 fluoro group Chemical group F* 0.000 description 26
230000008569 process Effects 0.000 description 25
239000002253 acid Substances 0.000 description 24
125000002947 alkylene group Chemical group 0.000 description 24
239000001294 propane Substances 0.000 description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
125000004494 ethyl ester group Chemical group 0.000 description 23
125000000262 haloalkenyl group Chemical group 0.000 description 23
230000002209 hydrophobic effect Effects 0.000 description 23
239000010410 layer Substances 0.000 description 23
239000002245 particle Substances 0.000 description 23
125000004994 halo alkoxy alkyl group Chemical group 0.000 description 21
125000002768 hydroxyalkyl group Chemical group 0.000 description 21
238000012360 testing method Methods 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
125000003710 aryl alkyl group Chemical group 0.000 description 20
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 19
150000002148 esters Chemical class 0.000 description 19
239000000463 material Substances 0.000 description 19
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 19
238000001694 spray drying Methods 0.000 description 19
125000004183 alkoxy alkyl group Chemical group 0.000 description 18
230000008018 melting Effects 0.000 description 17
238000002844 melting Methods 0.000 description 17
125000004104 aryloxy group Chemical group 0.000 description 16
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 16
125000002619 bicyclic group Chemical group 0.000 description 15
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 14
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 14
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
125000004438 haloalkoxy group Chemical group 0.000 description 14
125000006350 alkyl thio alkyl group Chemical group 0.000 description 13
125000005164 aryl thioalkyl group Chemical group 0.000 description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 13
230000007423 decrease Effects 0.000 description 13
125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 13
230000003993 interaction Effects 0.000 description 13
125000004390 alkyl sulfonyl group Chemical group 0.000 description 12
125000005110 aryl thio group Chemical group 0.000 description 12
229920002301 cellulose acetate Polymers 0.000 description 12
239000000843 powder Substances 0.000 description 12
125000005452 alkenyloxyalkyl group Chemical group 0.000 description 11
125000005160 aryl oxy alkyl group Chemical group 0.000 description 11
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
125000005553 heteroaryloxy group Chemical group 0.000 description 11
125000005844 heterocyclyloxy group Chemical group 0.000 description 11
125000001145 hydrido group Chemical group *[H] 0.000 description 11
239000002953 phosphate buffered saline Substances 0.000 description 11
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 10
125000003282 alkyl amino group Chemical group 0.000 description 10
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 10
229920006037 cross link polymer Polymers 0.000 description 10
238000012545 processing Methods 0.000 description 10
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
125000004434 sulfur atom Chemical group 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 description 9
125000003435 aroyl group Chemical group 0.000 description 9
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 9
235000010980 cellulose Nutrition 0.000 description 9
229920002678 cellulose Polymers 0.000 description 9
239000001913 cellulose Substances 0.000 description 9
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 9
238000001035 drying Methods 0.000 description 9
125000004446 heteroarylalkyl group Chemical group 0.000 description 9
125000005368 heteroarylthio group Chemical group 0.000 description 9
238000002156 mixing Methods 0.000 description 9
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 8
125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 description 8
125000004644 alkyl sulfinyl group Chemical group 0.000 description 8
125000005140 aralkylsulfonyl group Chemical group 0.000 description 8
125000005135 aryl sulfinyl group Chemical group 0.000 description 8
125000004391 aryl sulfonyl group Chemical group 0.000 description 8
125000002837 carbocyclic group Chemical group 0.000 description 8
150000003857 carboxamides Chemical class 0.000 description 8
125000004181 carboxyalkyl group Chemical group 0.000 description 8
125000005356 cycloalkylalkenyl group Chemical group 0.000 description 8
125000005144 cycloalkylsulfonyl group Chemical group 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
239000012530 fluid Substances 0.000 description 8
125000000232 haloalkynyl group Chemical group 0.000 description 8
125000006769 halocycloalkoxy group Chemical group 0.000 description 8
125000005347 halocycloalkyl group Chemical group 0.000 description 8
125000005150 heteroarylsulfinyl group Chemical group 0.000 description 8
125000005143 heteroarylsulfonyl group Chemical group 0.000 description 8
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 8
239000001863 hydroxypropyl cellulose Substances 0.000 description 8
229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
239000007921 spray Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
SHNMAZJVVFUXAQ-UHFFFAOYSA-N 2h-quinoline-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CC=CC2=C1 SHNMAZJVVFUXAQ-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
239000013078 crystal Substances 0.000 description 7
125000000000 cycloalkoxy group Chemical group 0.000 description 7
125000005149 cycloalkylsulfinyl group Chemical group 0.000 description 7
NIRMDYUESATWJX-UHFFFAOYSA-N cycloheptene-1-carboxamide Chemical compound NC(=O)C1=CCCCCC1 NIRMDYUESATWJX-UHFFFAOYSA-N 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 7
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 7
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 7
239000001267 polyvinylpyrrolidone Substances 0.000 description 7
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 6
102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 6
239000000654 additive Substances 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
125000004447 heteroarylalkenyl group Chemical group 0.000 description 6
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 6
239000002356 single layer Substances 0.000 description 6
102000015779 HDL Lipoproteins Human genes 0.000 description 5
108010010234 HDL Lipoproteins Proteins 0.000 description 5
125000004423 acyloxy group Chemical group 0.000 description 5
125000004450 alkenylene group Chemical group 0.000 description 5
125000005108 alkenylthio group Chemical group 0.000 description 5
125000005109 alkynylthio group Chemical group 0.000 description 5
229920001577 copolymer Polymers 0.000 description 5
125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
125000004663 dialkyl amino group Chemical group 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
125000004440 haloalkylsulfinyl group Chemical group 0.000 description 5
125000003106 haloaryl group Chemical group 0.000 description 5
125000005216 haloheteroaryl group Chemical group 0.000 description 5
125000004449 heterocyclylalkenyl group Chemical group 0.000 description 5
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