TW200524862A - Crystalline forms of [R-(R*, R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4[(phenylamino) carbonyl] -1H-pyrrole-1-heptanoic acid - Google Patents
Crystalline forms of [R-(R*, R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4[(phenylamino) carbonyl] -1H-pyrrole-1-heptanoic acid Download PDFInfo
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- TW200524862A TW200524862A TW093127885A TW93127885A TW200524862A TW 200524862 A TW200524862 A TW 200524862A TW 093127885 A TW093127885 A TW 093127885A TW 93127885 A TW93127885 A TW 93127885A TW 200524862 A TW200524862 A TW 200524862A
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- Prior art keywords
- free acid
- type
- atorvastatin
- atorvastatin free
- ray powder
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- 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 title claims abstract description 68
- 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 abstract description 66
- 229960005370 atorvastatin Drugs 0.000 claims abstract description 66
- 239000002253 acid Substances 0.000 claims abstract description 62
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 10
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 5
- 239000013078 crystal Substances 0.000 claims description 47
- 239000007787 solid Substances 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 20
- 239000000843 powder Substances 0.000 claims description 12
- 238000005481 NMR spectroscopy Methods 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 230000005855 radiation Effects 0.000 claims description 9
- 229910016523 CuKa Inorganic materials 0.000 claims description 7
- 150000004677 hydrates Chemical class 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- 210000002534 adenoid Anatomy 0.000 claims 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
- 238000005259 measurement Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 19
- 238000002360 preparation method Methods 0.000 abstract description 9
- 150000003839 salts Chemical class 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 abstract description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 238000000279 solid-state nuclear magnetic resonance spectrum Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 229910001868 water Inorganic materials 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 14
- 229960001770 atorvastatin calcium Drugs 0.000 description 14
- 239000000523 sample Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000009472 formulation Methods 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
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- 239000007937 lozenge Substances 0.000 description 6
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- 239000004480 active ingredient Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
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- 239000006187 pill Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 4
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000002050 international nonproprietary name Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 239000003524 antilipemic agent Substances 0.000 description 2
- -1 atorvastatin calcium Chemical compound 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
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- 239000002562 thickening agent Substances 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 description 1
- CJFVCTVYZFTORU-UHFFFAOYSA-N 2-methyl-2-methylsulfanylpropane Chemical compound CSC(C)(C)C CJFVCTVYZFTORU-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 244000241257 Cucumis melo Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920002302 Nylon 6,6 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102400001190 Vastatin Human genes 0.000 description 1
- 101800000422 Vastatin Proteins 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 238000004164 analytical calibration Methods 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000005586 carbonic acid group Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005388 cross polarization Methods 0.000 description 1
- 238000005384 cross polarization magic-angle spinning Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 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 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
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- 239000007920 enema Substances 0.000 description 1
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- 238000000605 extraction Methods 0.000 description 1
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- 229930195729 fatty acid Natural products 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002075 inversion recovery Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000968 medical method and process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
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- 150000004684 trihydrates Chemical class 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50359203P | 2003-09-17 | 2003-09-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200524862A true TW200524862A (en) | 2005-08-01 |
Family
ID=34312443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW093127885A TW200524862A (en) | 2003-09-17 | 2004-09-15 | Crystalline forms of [R-(R*, R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4[(phenylamino) carbonyl] -1H-pyrrole-1-heptanoic acid |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20070276027A1 (enExample) |
| EP (1) | EP1663969A1 (enExample) |
| JP (1) | JP2007505885A (enExample) |
| KR (1) | KR100781420B1 (enExample) |
| CN (2) | CN101318923A (enExample) |
| AR (1) | AR045654A1 (enExample) |
| AU (1) | AU2004272365A1 (enExample) |
| BR (1) | BRPI0414457A (enExample) |
| CA (1) | CA2539158A1 (enExample) |
| IL (1) | IL173651A0 (enExample) |
| MX (1) | MXPA06003003A (enExample) |
| NO (1) | NO20060716L (enExample) |
| RU (1) | RU2315755C2 (enExample) |
| TW (1) | TW200524862A (enExample) |
| WO (1) | WO2005026116A1 (enExample) |
| ZA (1) | ZA200602222B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080007561A (ko) | 2005-12-13 | 2008-01-22 | 테바 파마슈티컬 인더스트리즈 리미티드 | 아토바스타틴 헤미칼슘의 결정형 및 이의 제조 방법 |
| MX2009011009A (es) * | 2007-04-13 | 2009-10-30 | Nicox Sa | Formas cristalinas de atorvastatin 4-(nitrooxi)butil ester. |
| US8697740B2 (en) | 2009-01-12 | 2014-04-15 | Merck Sharp & Dohme Corp. | Crystalline polymorphic forms of an antidiabetic compound |
| CA3065589C (en) | 2010-06-03 | 2022-04-26 | Catalent Ontario Limited | Multi phase soft gel capsules, apparatus and method thereof |
| CA2706270C (en) * | 2010-06-03 | 2020-01-07 | Accucaps Industries Limited | Pharmaceutical formulations of statins and omega-3 fatty acids for encapsulation |
| KR20120011249A (ko) | 2010-07-28 | 2012-02-07 | 주식회사 경보제약 | 아토바스타틴 헤미칼슘염의 신규한 결정형, 이의 수화물, 및 그의 제조방법 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4681873A (en) * | 1985-07-29 | 1987-07-21 | Warner-Lambert Company | 4-amino-3-halo-2-pyridinone nucleoside and nucleotide compounds |
| US4681893A (en) | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| US5216174A (en) * | 1988-02-22 | 1993-06-01 | Warner-Lambert Co. | Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5149837A (en) * | 1988-02-22 | 1992-09-22 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5003080A (en) * | 1988-02-22 | 1991-03-26 | Warner-Lambert Company | Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis |
| US5245047A (en) * | 1988-02-22 | 1993-09-14 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5124482A (en) * | 1988-02-22 | 1992-06-23 | Warner-Lambert Company | Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-2-one inhibitors of cholesterol synthesis |
| US5097045A (en) * | 1989-02-01 | 1992-03-17 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| FI94339C (fi) * | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| US5248793A (en) * | 1990-10-17 | 1993-09-28 | Warner-Lambert Company | Process for the synthesis of (4R-cis)-1,1-dimethylethyl 6-iodomethyl or 6-(phenyl-substituted)sulfonyloxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
| US5103024A (en) * | 1990-10-17 | 1992-04-07 | Warner-Lambert Company | Process for the synthesis of (4r-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
| US5155251A (en) * | 1991-10-11 | 1992-10-13 | Warner-Lambert Company | Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate |
| US5213995A (en) * | 1992-04-16 | 1993-05-25 | At&T Bell Laboratories | Method of making an article comprising a periodic heteroepitaxial semiconductor structure |
| WO1994016693A1 (en) * | 1993-01-19 | 1994-08-04 | Warner-Lambert Company | Stable oral ci-981 formulation and process of preparing same |
| US5298627A (en) * | 1993-03-03 | 1994-03-29 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| HRP960313B1 (en) * | 1995-07-17 | 2002-08-31 | Warner Lambert Co | Form iii crystalline (r- (r*, r*)-2- (4-fluorophenyl) -beta-delta-hydroxy-5-(1-methylethyl) -3-phenyl-4- ((phenylamino) carbonyl -1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
| ES2167587T3 (es) * | 1995-07-17 | 2002-05-16 | Warner Lambert Co | Forma cristalina de la sal hemicalcica del acido (r-(r*,r*))-2-(4-fluorofenil)-beta,delta-dihidroxi-5-(1-metiletil)-3-fenil-4-((fenilamino)carbonil)-1h-pirrol-1-heptanoico (atorvastatina). |
| US6087511A (en) * | 1996-07-16 | 2000-07-11 | Warner-Lambert Company | Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl )-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid) calcium salt (2:1) |
| EP0915866B1 (en) * | 1996-07-29 | 2002-03-27 | Warner-Lambert Company | Improved process for the synthesis of protected esters of (s)-3,4-dihydroxybutyric acid |
| HUP0100252A3 (en) * | 1997-12-19 | 2002-12-28 | Warner Lambert Exp Ltd Dun Lao | Process for the synthesis of 1,3-diols |
| SI20070A (sl) * | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Nove soli inhibitorjev HMG-CoA reduktaze |
| AU3289102A (en) * | 2000-11-16 | 2002-06-11 | Teva Pharma | Hydrolysis of (R(R*,R*))-2-(4-fluorophenyl)-beta,delta -dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino) carbonyl)-1H-pyrrole-1-heptanoic acid esters with calcium hydroxide |
| US6476235B2 (en) * | 2001-01-09 | 2002-11-05 | Warner-Lambert Company | Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide |
-
2004
- 2004-09-06 US US10/572,324 patent/US20070276027A1/en not_active Abandoned
- 2004-09-06 WO PCT/IB2004/002919 patent/WO2005026116A1/en not_active Ceased
- 2004-09-06 CN CNA2008101341489A patent/CN101318923A/zh active Pending
- 2004-09-06 RU RU2006108385/04A patent/RU2315755C2/ru not_active IP Right Cessation
- 2004-09-06 BR BRPI0414457-0A patent/BRPI0414457A/pt not_active IP Right Cessation
- 2004-09-06 MX MXPA06003003A patent/MXPA06003003A/es unknown
- 2004-09-06 EP EP04769318A patent/EP1663969A1/en not_active Withdrawn
- 2004-09-06 AU AU2004272365A patent/AU2004272365A1/en not_active Abandoned
- 2004-09-06 KR KR1020067005316A patent/KR100781420B1/ko not_active Expired - Fee Related
- 2004-09-06 JP JP2006526717A patent/JP2007505885A/ja active Pending
- 2004-09-06 CN CNA2004800269756A patent/CN1852894A/zh active Pending
- 2004-09-06 CA CA002539158A patent/CA2539158A1/en not_active Abandoned
- 2004-09-15 TW TW093127885A patent/TW200524862A/zh unknown
- 2004-09-15 AR ARP040103296A patent/AR045654A1/es unknown
-
2006
- 2006-02-09 IL IL173651A patent/IL173651A0/en unknown
- 2006-02-14 NO NO20060716A patent/NO20060716L/no not_active Application Discontinuation
- 2006-03-16 ZA ZA200602222A patent/ZA200602222B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL173651A0 (en) | 2006-07-05 |
| ZA200602222B (en) | 2007-07-25 |
| BRPI0414457A (pt) | 2006-11-14 |
| EP1663969A1 (en) | 2006-06-07 |
| MXPA06003003A (es) | 2006-06-23 |
| CN1852894A (zh) | 2006-10-25 |
| AR045654A1 (es) | 2005-11-02 |
| CN101318923A (zh) | 2008-12-10 |
| KR20060037467A (ko) | 2006-05-03 |
| RU2006108385A (ru) | 2006-08-10 |
| US20070276027A1 (en) | 2007-11-29 |
| AU2004272365A1 (en) | 2005-03-24 |
| CA2539158A1 (en) | 2005-03-24 |
| JP2007505885A (ja) | 2007-03-15 |
| RU2315755C2 (ru) | 2008-01-27 |
| NO20060716L (no) | 2006-06-16 |
| WO2005026116A1 (en) | 2005-03-24 |
| KR100781420B1 (ko) | 2007-12-03 |
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