CA2392979A1 - Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine - Google Patents

Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine Download PDF

Info

Publication number: CA2392979A1
Authority: CA; Canada
Prior art keywords: crystal; trifluoromethyl; formula; rel; dihydro
Prior art date: 1999-11-30
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002392979A

Other languages

English (en)

Inventor

Douglas John Meldrum Allen

Lyle Robinson Brostrom

Troy Anthony Appleton

Derek Lawrence Tickner

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pfizer Products Inc

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-11-30

Filing date

2000-11-14

Publication date

2001-06-07

2000-11-14 Application filed by Individual filed Critical Individual

2001-06-07 Publication of CA2392979A1 publication Critical patent/CA2392979A1/fr

Status Abandoned legal-status Critical Current

Links

239000013078 crystal Substances 0.000 title claims abstract description 100
-1 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinoline Chemical class 0.000 title description 6
238000000034 method Methods 0.000 claims abstract description 49
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 78
241000124008 Mammalia Species 0.000 claims description 70
150000001875 compounds Chemical class 0.000 claims description 40
239000008194 pharmaceutical composition Substances 0.000 claims description 36
239000003937 drug carrier Substances 0.000 claims description 29
239000003085 diluting agent Substances 0.000 claims description 28
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 28
239000003981 vehicle Substances 0.000 claims description 26
201000001320 Atherosclerosis Diseases 0.000 claims description 21
208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 18
201000001386 familial hypercholesterolemia Diseases 0.000 claims description 18
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 claims description 17
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 17
208000032928 Dyslipidaemia Diseases 0.000 claims description 12
208000017170 Lipid metabolism disease Diseases 0.000 claims description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
208000024172 Cardiovascular disease Diseases 0.000 claims description 11
208000008589 Obesity Diseases 0.000 claims description 11
235000020824 obesity Nutrition 0.000 claims description 11
206010002383 Angina Pectoris Diseases 0.000 claims description 9
208000037487 Endotoxemia Diseases 0.000 claims description 9
208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
206010020772 Hypertension Diseases 0.000 claims description 9
206010021024 Hypolipidaemia Diseases 0.000 claims description 9
102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 9
208000018262 Peripheral vascular disease Diseases 0.000 claims description 9
206010063837 Reperfusion injury Diseases 0.000 claims description 9
208000006011 Stroke Diseases 0.000 claims description 9
206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 9
206010012601 diabetes mellitus Diseases 0.000 claims description 9
208000006575 hypertriglyceridemia Diseases 0.000 claims description 9
208000029498 hypoalphalipoproteinemia Diseases 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
208000010125 myocardial infarction Diseases 0.000 claims description 9
208000037803 restenosis Diseases 0.000 claims description 9
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208000028867 ischemia Diseases 0.000 claims description 7
238000002156 mixing Methods 0.000 claims description 7
208000031225 myocardial ischemia Diseases 0.000 claims description 7
238000000634 powder X-ray diffraction Methods 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
WGLUDAOFIMTWAM-WKOQGQMTSA-N ethanol;ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound CCO.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 WGLUDAOFIMTWAM-WKOQGQMTSA-N 0.000 claims description 5
238000009499 grossing Methods 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 2
239000002243 precursor Substances 0.000 claims 3
KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 claims 2
102100037637 Cholesteryl ester transfer protein Human genes 0.000 claims 2
101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 claims 2
239000010685 fatty oil Substances 0.000 claims 2
230000002401 inhibitory effect Effects 0.000 claims 2
239000000203 mixture Substances 0.000 abstract description 30
239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 abstract description 3
229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 17
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000003112 inhibitor Substances 0.000 description 13
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000007787 solid Substances 0.000 description 11
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 10
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
208000029078 coronary artery disease Diseases 0.000 description 9
239000000843 powder Substances 0.000 description 9
239000002002 slurry Substances 0.000 description 9
108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 8
102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 8
108010010234 HDL Lipoproteins Proteins 0.000 description 8
102000015779 HDL Lipoproteins Human genes 0.000 description 8
239000000463 material Substances 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 7
238000002072 distortionless enhancement with polarization transfer spectrum Methods 0.000 description 7
108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
150000002632 lipids Chemical class 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
108010023302 HDL Cholesterol Proteins 0.000 description 4
238000008214 LDL Cholesterol Methods 0.000 description 4
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PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
238000002441 X-ray diffraction Methods 0.000 description 4
239000002775 capsule Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
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 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
229940125753 fibrate Drugs 0.000 description 4
238000001914 filtration Methods 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
229960003512 nicotinic acid Drugs 0.000 description 4
235000001968 nicotinic acid Nutrition 0.000 description 4
239000011664 nicotinic acid Substances 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].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 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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 description 3
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 description 3
229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 3
229940123239 Cholesterol synthesis inhibitor Drugs 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
108010028554 LDL Cholesterol Proteins 0.000 description 3
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 description 3
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 description 3
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 description 3
239000003963 antioxidant agent Substances 0.000 description 3
230000003078 antioxidant effect Effects 0.000 description 3
229960005370 atorvastatin Drugs 0.000 description 3
229920000080 bile acid sequestrant Polymers 0.000 description 3
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 description 3
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AZFYCLSCZLWMBW-PWSUYJOCSA-N ethyl (2r,4s)-4-amino-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound FC(F)(F)C1=CC=C2N(C(=O)OCC)[C@H](CC)C[C@H](N)C2=C1 AZFYCLSCZLWMBW-PWSUYJOCSA-N 0.000 description 3
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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 description 3
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CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
241000233866 Fungi Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 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
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
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241000288906 Primates Species 0.000 description 1
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VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
230000009471 action Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
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230000004075 alteration Effects 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
230000000879 anti-atherosclerotic effect Effects 0.000 description 1
230000003143 atherosclerotic effect Effects 0.000 description 1
230000006399 behavior Effects 0.000 description 1
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
239000012964 benzotriazole Substances 0.000 description 1
YGBQZFPEMRCQRY-UHFFFAOYSA-N benzyl n-ethenylcarbamate Chemical compound C=CNC(=O)OCC1=CC=CC=C1 YGBQZFPEMRCQRY-UHFFFAOYSA-N 0.000 description 1
239000003613 bile acid Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
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235000019693 cherries Nutrition 0.000 description 1
239000007958 cherry flavor Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
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238000013270 controlled release Methods 0.000 description 1
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230000002939 deleterious effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000001434 dietary modification Nutrition 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000000499 gel Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
208000023589 ischemic disease Diseases 0.000 description 1
239000008101 lactose Substances 0.000 description 1
XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
244000144972 livestock Species 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000007968 orange flavor Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000000207 pro-atherogenic effect Effects 0.000 description 1
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235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
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238000003786 synthesis reaction Methods 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000006208 topical dosage form Substances 0.000 description 1
125000005490 tosylate group Chemical class 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- A61P3/04—Anorexiants; Antiobesity agents
- 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
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Cephalosporin Compounds (AREA)
Quinoline Compounds (AREA)

CA002392979A 1999-11-30 2000-11-14 Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine Abandoned CA2392979A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US16805199P	1999-11-30	1999-11-30
US60/168,051		1999-11-30
PCT/IB2000/001650 WO2001040190A1 (fr)	1999-11-30	2000-11-14	Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine utilises en tant qu'inhibiteurs de cetp

Publications (1)

Publication Number	Publication Date
CA2392979A1 true CA2392979A1 (fr)	2001-06-07

Family

ID=22609901

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002392979A Abandoned CA2392979A1 (fr)	1999-11-30	2000-11-14	Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine

Country Status (28)

Country	Link
EP (1)	EP1246804A1 (fr)
JP (1)	JP2003515592A (fr)
KR (1)	KR20020058057A (fr)
CN (1)	CN1402711A (fr)
AP (1)	AP2002002531A0 (fr)
AU (1)	AU1048801A (fr)
BG (1)	BG106854A (fr)
BR (1)	BR0015836A (fr)
CA (1)	CA2392979A1 (fr)
CO (1)	CO5271716A1 (fr)
EA (1)	EA200200510A1 (fr)
EC (1)	ECSP003792A (fr)
EE (1)	EE200200277A (fr)
GT (1)	GT200000199A (fr)
HU (1)	HUP0203521A2 (fr)
IL (1)	IL149097A0 (fr)
IS (1)	IS6338A (fr)
MA (1)	MA26845A1 (fr)
MX (1)	MXPA02005354A (fr)
NO (1)	NO20022558D0 (fr)
OA (1)	OA12099A (fr)
PA (1)	PA8506301A1 (fr)
PE (1)	PE20010904A1 (fr)
PL (1)	PL355892A1 (fr)
TN (1)	TNSN00231A1 (fr)
TR (1)	TR200201446T2 (fr)
UY (1)	UY26454A1 (fr)
WO (1)	WO2001040190A1 (fr)

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US7115279B2 (en)	2000-08-03	2006-10-03	Curatolo William J	Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors
EA200301139A1 (ru)	2001-06-21	2004-12-30	Пфайзер Продактс Инк.	Самоэмульгирующиеся препараты ингибиторов белка-переносчика эфиров холестерина
GT200200170A (es)	2001-09-28	2003-05-23		Preparacion de inhibidor de cetp anhidro
DE60320940D1 (de)	2002-02-01	2008-06-26	Pfizer Prod Inc	Pharmazeutische zusammensetzungen amorpher dispersionen von wirkstoffen und lipophiler mikrophasenbildender materialien
PL372247A1 (en) *	2002-02-01	2005-07-11	Pfizer Products Inc.	Method for making homogeneous spray-dried solid amorphous drug dispersions utilizing modified spray-drying apparatus
EP1920766B1 (fr) *	2002-02-01	2017-08-23	Bend Research, Inc	Compositions pharmaceutiques de dispersions amorphes de médicaments et matériaux formant des microphases lipophiles
US7332514B2 (en)	2002-08-30	2008-02-19	Japan Tobacco Inc.	Dibenzylamine compound and medicinal use thereof
US7504508B2 (en)	2002-10-04	2009-03-17	Millennium Pharmaceuticals, Inc.	PGD2 receptor antagonists for the treatment of inflammatory diseases
WO2004032848A2 (fr)	2002-10-04	2004-04-22	Millennium Pharmaceuticals, Inc.	Antagonistes vis-a-vis du recepteur pgd2 pour le traitement de maladies inflammatoires
US20040132771A1 (en) *	2002-12-20	2004-07-08	Pfizer Inc	Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors
JP2006513186A (ja)	2002-12-20	2006-04-20	ファイザー・プロダクツ・インク	Ｃｅｔｐ阻害剤およびｈｍｇ−ｃｏａレダクターゼ阻害剤を含む剤形
WO2004082675A1 (fr)	2003-03-17	2004-09-30	Japan Tobacco Inc.	Procede pour accroitre la biodisponibilite orale de s- [2- ([[1- (2-ethylbutyl) cyclohexyl] carbonyl] amino) phenyl] -2-methylpropanethioate
JP2006521344A (ja) *	2003-03-28	2006-09-21	ファイザー・プロダクツ・インク	アテローム性動脈硬化症および肥満の治療のためのｃｅｔｐ阻害剤としての１，２，４−置換１，２，３，４−テトラヒドロ−および１，２−ジヒドロ−キノリンおよび１，２，３，４−テトラヒドロ−キノキサリン誘導体
BRPI0413277A (pt)	2003-08-04	2006-10-10	Pfizer Prod Inc	composições farmacêuticas de adsorvatos de medicamentos amorfos e materiais que formam microfases lipofìlicas
DE602004023100D1 (de)	2003-10-08	2009-10-22	Lilly Co Eli	Verbindungen und verfahren zur behandlung von dyslipidemie
CA2562082C (fr) *	2004-04-13	2013-06-25	Merck & Co., Inc.	Inhibiteurs de la cetp pour le traitement et la prevention de l'atherosclerose
EA200700119A1 (ru) *	2004-06-24	2007-10-26	Эли Лилли Энд Компани	Соединения и способы лечения дислипидемии
WO2006033004A1 (fr) *	2004-09-23	2006-03-30	Pfizer Products Inc.	Composes de quinoline en tant qu'inhibiteurs de cetp
WO2006033001A1 (fr) *	2004-09-23	2006-03-30	Pfizer Products Inc.	Composes de quinoline
WO2006091674A1 (fr)	2005-02-24	2006-08-31	Millennium Pharmaceuticals, Inc.	Antagonistes de recepteur de pgd2 pour le traitement des maladies inflammatoires
WO2006098394A1 (fr) *	2005-03-14	2006-09-21	Japan Tobacco Inc.	Méthode pour inhiber l’absorption de lipides et l’inhibiteur de l'absorption de lipides
US7737155B2 (en)	2005-05-17	2010-06-15	Schering Corporation	Nitrogen-containing heterocyclic compounds and methods of use thereof
CL2008000684A1 (es)	2007-03-09	2008-08-01	Indigene Pharmaceuticals Inc	Composicion farmaceutica que comprende metformina r-(+) lipoato y un inhibidor de reductasa hmg-coa; formulacion de dosis unitaria; y uso en el tratamiento de una complicacion diabetica.
EP2379547A1 (fr)	2008-12-16	2011-10-26	Schering Corporation	Dérivés de pyridopyrimidine et leurs procédés d'utilisation
US20110243940A1 (en)	2008-12-16	2011-10-06	Schering Corporation	Bicyclic pyranone derivatives and methods of use thereof
TWI450896B (zh)	2009-06-30	2014-09-01	Lilly Co Eli	反式－４－〔〔（５ｓ）－５－〔〔〔３，５－雙（三氟甲基）苯基〕甲基〕（２－甲基－２ｈ－四唑－５－基）胺基〕－２，３，４，５－四氫－７，９－二甲基－１ｈ－１－苯并氮呯－１－基〕甲基〕－環己基羧酸
MX384679B (es)	2014-07-30	2025-03-14	Hoffmann La Roche	Marcadores genéticos para predecir la reactividad a terapia con agente que eleva la lipoproteína de alta densidad (hdl) o que imita la lipoproteína de alta densidad (hdl).

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US5231102A (en) *	1989-03-08	1993-07-27	Merck Sharp & Dohme, Ltd.	Tetrahydroquinoline derivatives useful for neurodegenerative disorders
AU5731098A (en) *	1997-02-03	1998-08-25	American Home Products Corporation	2-substituted-1-acyl-1,2-dihydroquinoline derivatives to increase hdl-cholesterol level
US6197786B1 (en) *	1998-09-17	2001-03-06	Pfizer Inc	4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines

2000
- 2000-11-09 CO CO00085285A patent/CO5271716A1/es unknown
- 2000-11-13 PA PA20008506301A patent/PA8506301A1/es unknown
- 2000-11-14 BR BR0015836-4A patent/BR0015836A/pt not_active IP Right Cessation
- 2000-11-14 KR KR1020027006914A patent/KR20020058057A/ko not_active Ceased
- 2000-11-14 CA CA002392979A patent/CA2392979A1/fr not_active Abandoned
- 2000-11-14 TR TR2002/01446T patent/TR200201446T2/xx unknown
- 2000-11-14 CN CN00816463A patent/CN1402711A/zh active Pending
- 2000-11-14 IL IL14909700A patent/IL149097A0/xx unknown
- 2000-11-14 EA EA200200510A patent/EA200200510A1/ru unknown
- 2000-11-14 OA OA1200200158A patent/OA12099A/en unknown
- 2000-11-14 AP APAP/P/2002/002531A patent/AP2002002531A0/en unknown
- 2000-11-14 AU AU10488/01A patent/AU1048801A/en not_active Abandoned
- 2000-11-14 EP EP00971662A patent/EP1246804A1/fr not_active Withdrawn
- 2000-11-14 HU HU0203521A patent/HUP0203521A2/hu unknown
- 2000-11-14 MX MXPA02005354A patent/MXPA02005354A/es unknown
- 2000-11-14 JP JP2001541875A patent/JP2003515592A/ja active Pending
- 2000-11-14 WO PCT/IB2000/001650 patent/WO2001040190A1/fr not_active Ceased
- 2000-11-14 EE EEP200200277A patent/EE200200277A/xx unknown
- 2000-11-14 PL PL00355892A patent/PL355892A1/xx not_active Application Discontinuation
- 2000-11-28 UY UY26454A patent/UY26454A1/es not_active Application Discontinuation
- 2000-11-28 PE PE2000001267A patent/PE20010904A1/es not_active Application Discontinuation
- 2000-11-29 GT GT200000199A patent/GT200000199A/es unknown
- 2000-11-29 EC EC2000003792A patent/ECSP003792A/es unknown
- 2000-11-29 TN TNTNSN00231A patent/TNSN00231A1/fr unknown
2002
- 2002-04-12 IS IS6338A patent/IS6338A/is unknown
- 2002-05-27 MA MA26653A patent/MA26845A1/fr unknown
- 2002-05-29 NO NO20022558A patent/NO20022558D0/no not_active Application Discontinuation
- 2002-06-20 BG BG106854A patent/BG106854A/bg unknown

Also Published As

Publication number	Publication date
NO20022558L (no)	2002-05-29
EA200200510A1 (ru)	2002-10-31
WO2001040190A1 (fr)	2001-06-07
BR0015836A (pt)	2002-08-06
BG106854A (bg)	2002-12-29
IS6338A (is)	2002-04-12
ECSP003792A (es)	2002-04-23
JP2003515592A (ja)	2003-05-07
PL355892A1 (en)	2004-05-31
KR20020058057A (ko)	2002-07-12
OA12099A (en)	2006-05-04
CO5271716A1 (es)	2003-04-30
UY26454A1 (es)	2001-07-31
AU1048801A (en)	2001-06-12
HUP0203521A2 (hu)	2003-02-28
NO20022558D0 (no)	2002-05-29
PE20010904A1 (es)	2001-09-10
EE200200277A (et)	2003-10-15
GT200000199A (es)	2002-05-23
TR200201446T2 (tr)	2002-11-21
MA26845A1 (fr)	2004-12-20
EP1246804A1 (fr)	2002-10-09
MXPA02005354A (es)	2002-12-11
AP2002002531A0 (en)	2002-06-30
TNSN00231A1 (fr)	2002-05-30
IL149097A0 (en)	2002-11-10
CN1402711A (zh)	2003-03-12
PA8506301A1 (es)	2002-08-26

Legal Events

Date	Code	Title	Description
2002-05-29	EEER	Examination request
2004-11-15	FZDE	Discontinued

Publication	Publication Date	Title
CA2327029C (fr)	2005-08-09	Methode pour fabriquer de la 1,2,3,4-tetrahydroquinoline substituee au 4-carboxyamino-2
CA2392979A1 (fr)	2001-06-07	Cristaux de 4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoleine
DE69917400T2 (de)	2005-05-19	4-Carboxyamino-2-Methyl-1,2,3,4-Tetrahydrochinoline als CETP-Hemmer
DE69926582T2 (de)	2006-03-30	Anellierte 4-Carboxyamino-2-Methyl-1,2,3,4-Tetrahydrochinoline als CETP-Hemmer
DE69917790T2 (de)	2005-06-09	4-amino substituierte -2-subsituierte-1,2,3,4-tetrahydrochinoline als cetp inhibitoren
US6147090A (en)	2000-11-14	4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines
DE69925845T2 (de)	2006-05-18	4-carboxamino-2-subsitutierte-1,2,3,4-tetrahydrochinoline als cetp inhibitoren
US5112817A (en)	1992-05-12	Quinoline derivatives
MXPA00011855A (en)	2002-06-05	Method for making (-)-(2r,4s)-4- [(3,5-bis- trifluoromethyl-benzyl)- methoxycarbonylamino]- 2-ethyl-6- trifluoromethyl-3,4-dihydro- 2h-quinoline- 1-carboxylic acid ethyl ester
CA2090635A1 (fr)	1993-09-04	Derives phenylquinazoline substitues
HK1038007B (en)	2005-04-08	Method for making 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinoline