UA78564C2 - Diphenylacetidinon derivatives for treatment of disordered lipid metabolism, method of production thereof(variants), pharmaceutical composition - Google Patents

Diphenylacetidinon derivatives for treatment of disordered lipid metabolism, method of production thereof(variants), pharmaceutical composition Download PDF

Info

Publication number: UA78564C2
Authority: UA; Ukraine
Prior art keywords: solvate; formula; group; alkyl; compound
Prior art date: 2002-07-05

Application number

UA20041210110A

Other languages

English (en)

Ukrainian (uk)

Inventor

Mikael Ulf Johan Dahlstrom

Mats Peter Nordberg

Malin Anita Lemurell

Original Assignee

Astrazeneca Ab

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.)

2002-07-05

Filing date

2003-01-07

Publication date

2007-04-10

2003-01-07 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2007-04-10 Publication of UA78564C2 publication Critical patent/UA78564C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 142
238000011282 treatment Methods 0.000 title claims abstract description 47
238000004519 manufacturing process Methods 0.000 title claims abstract description 21
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
230000037356 lipid metabolism Effects 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 404
239000012453 solvate Substances 0.000 claims abstract description 394
150000001875 compounds Chemical class 0.000 claims abstract description 326
229940002612 prodrug Drugs 0.000 claims abstract description 199
239000000651 prodrug Substances 0.000 claims abstract description 199
239000003112 inhibitor Substances 0.000 claims abstract description 61
-1 nitro, cyano, hydroxy, amino, carboxy, formyl Chemical group 0.000 claims description 360
125000000217 alkyl group Chemical group 0.000 claims description 240
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 202
239000001257 hydrogen Substances 0.000 claims description 202
229910052739 hydrogen Inorganic materials 0.000 claims description 202
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 117
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 112
125000000623 heterocyclic group Chemical group 0.000 claims description 97
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 96
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 claims description 92
229910052799 carbon Inorganic materials 0.000 claims description 90
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims description 89
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 88
150000002431 hydrogen Chemical class 0.000 claims description 87
150000001721 carbon Chemical group 0.000 claims description 85
229910052736 halogen Inorganic materials 0.000 claims description 79
150000002367 halogens Chemical class 0.000 claims description 79
125000001424 substituent group Chemical group 0.000 claims description 77
125000004452 carbocyclyl group Chemical group 0.000 claims description 76
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
241001465754 Metazoa Species 0.000 claims description 58
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 58
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
229910052757 nitrogen Inorganic materials 0.000 claims description 45
238000006243 chemical reaction Methods 0.000 claims description 44
235000012000 cholesterol Nutrition 0.000 claims description 42
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 41
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 34
150000002829 nitrogen Chemical class 0.000 claims description 33
241000282412 Homo Species 0.000 claims description 32
230000002401 inhibitory effect Effects 0.000 claims description 32
239000003814 drug Substances 0.000 claims description 23
239000003085 diluting agent Substances 0.000 claims description 22
230000001225 therapeutic effect Effects 0.000 claims description 22
125000006239 protecting group Chemical group 0.000 claims description 21
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 18
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
241000282414 Homo sapiens Species 0.000 claims description 17
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 17
238000010521 absorption reaction Methods 0.000 claims description 16
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 16
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 13
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
239000011737 fluorine Substances 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 12
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 11
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
OPISVEPYALEQJT-UHFFFAOYSA-N 1-phenylazetidin-2-one Chemical compound O=C1CCN1C1=CC=CC=C1 OPISVEPYALEQJT-UHFFFAOYSA-N 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 9
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
229910052796 boron Inorganic materials 0.000 claims description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 4
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 4
125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 4
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
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 4
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 4
229960005370 atorvastatin Drugs 0.000 claims 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 claims description 3
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 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 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
229960003765 fluvastatin Drugs 0.000 claims description 3
229960000672 rosuvastatin Drugs 0.000 claims description 3
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 description 3
229960002855 simvastatin Drugs 0.000 claims description 3
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 description 3
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 description 2
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 description 2
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 description 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 description 2
229950005357 bervastatin Drugs 0.000 claims description 2
229960005110 cerivastatin Drugs 0.000 claims description 2
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 description 2
229950003040 dalvastatin Drugs 0.000 claims description 2
ZADJRRFMOOACHL-WQICJITCSA-N ethyl (e,3s,5r)-7-[4-(4-fluorophenyl)spiro[chromene-2,1'-cyclopentane]-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C12=CC=CC=C2OC2(CCCC2)C(/C=C/[C@H](O)C[C@H](O)CC(=O)OCC)=C1C1=CC=C(F)C=C1 ZADJRRFMOOACHL-WQICJITCSA-N 0.000 claims description 2
229960004844 lovastatin Drugs 0.000 claims description 2
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 description 2
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 description 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 description 2
229950009116 mevastatin Drugs 0.000 claims description 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 description 2
229960002965 pravastatin Drugs 0.000 claims description 2
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 description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
241000611750 Coregonus kiyi Species 0.000 claims 1
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
230000001906 cholesterol absorption Effects 0.000 abstract description 16
230000008569 process Effects 0.000 abstract description 3
208000031226 Hyperlipidaemia Diseases 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
239000002904 solvent Substances 0.000 description 76
239000000243 solution Substances 0.000 description 68
230000002829 reductive effect Effects 0.000 description 59
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 58
239000000203 mixture Substances 0.000 description 54
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 46
239000005695 Ammonium acetate Substances 0.000 description 46
235000019257 ammonium acetate Nutrition 0.000 description 46
229940043376 ammonium acetate Drugs 0.000 description 46
239000000872 buffer Substances 0.000 description 45
239000003480 eluent Substances 0.000 description 43
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
238000002953 preparative HPLC Methods 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 29
235000019253 formic acid Nutrition 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
239000007787 solid Substances 0.000 description 26
150000002148 esters Chemical class 0.000 description 24
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 22
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 18
239000002552 dosage form Substances 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
230000015572 biosynthetic process Effects 0.000 description 16
125000001589 carboacyl group Chemical group 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
239000000556 agonist Substances 0.000 description 13
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CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
230000009102 absorption Effects 0.000 description 12
239000003613 bile acid Substances 0.000 description 11
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
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URSRDDAXMAGFTC-KXXDLYTDSA-N [(2s,3s,4s,5r,6r)-5-hydroxy-2-methyl-6-[[(2r,3s,4s,5r,6r)-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)ethoxy]oxan-2-yl]methoxy]-4-[(2s,3r,4s,5r)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-3-yl] (e)-3-(3,4-dimethoxyphenyl)prop-2-enoate Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)O[C@@H]1[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)CO2)O)[C@@H](O)[C@H](OC[C@@H]2[C@H]([C@H](O)[C@@H](O)[C@H](OCCC=3C=CC(O)=CC=3)O2)O)O[C@H]1C URSRDDAXMAGFTC-KXXDLYTDSA-N 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
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230000000694 effects Effects 0.000 description 8
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238000000859 sublimation Methods 0.000 description 8
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BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 8
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WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
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HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
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DAEAKVVPRJTPEQ-CSCXCSGISA-N teprotide Chemical compound N([C@@H](CC=1[C]2C=CC=CC2=NC=1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCC(=O)N1 DAEAKVVPRJTPEQ-CSCXCSGISA-N 0.000 description 1
VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
229960001909 terazosin hydrochloride Drugs 0.000 description 1
SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
MTKNGOHFNXIVOS-UHFFFAOYSA-N ticlopidine hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 MTKNGOHFNXIVOS-UHFFFAOYSA-N 0.000 description 1
229960002961 ticlopidine hydrochloride Drugs 0.000 description 1
229960004605 timolol Drugs 0.000 description 1
229960005221 timolol maleate Drugs 0.000 description 1
229960005062 tinzaparin Drugs 0.000 description 1
229950003004 tolamolol Drugs 0.000 description 1
229950005772 tosifen Drugs 0.000 description 1
231100000583 toxicological profile Toxicity 0.000 description 1
229960002051 trandolapril Drugs 0.000 description 1
AHYHTSYNOHNUSH-HXFGRODQSA-N trandolaprilat Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)C(O)=O)CC1=CC=CC=C1 AHYHTSYNOHNUSH-HXFGRODQSA-N 0.000 description 1
229960002651 trandolaprilat Drugs 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
230000008733 trauma Effects 0.000 description 1
229950001407 trifenagrel Drugs 0.000 description 1
229950005696 utibapril Drugs 0.000 description 1
229960004699 valsartan Drugs 0.000 description 1
SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
230000006492 vascular dysfunction Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
229960002647 warfarin sodium Drugs 0.000 description 1
229950009999 zabicipril Drugs 0.000 description 1
229950005973 zabiciprilat Drugs 0.000 description 1
DFKDOZMCHOGOBR-NCSQYGPNSA-N zaragozic acid A Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CC[C@]12[C@H](O)[C@H]([C@](O2)(C(O)=O)[C@@](O)([C@H](O1)C(O)=O)C(O)=O)OC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)C1=CC=CC=C1 DFKDOZMCHOGOBR-NCSQYGPNSA-N 0.000 description 1
DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
229960002769 zofenopril Drugs 0.000 description 1
IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 0.000 description 1
UQWLOWFDKAFKAP-WXHSDQCUSA-N zofenoprilat Chemical compound C1[C@@H](C(O)=O)N(C(=O)[C@@H](CS)C)C[C@H]1SC1=CC=CC=C1 UQWLOWFDKAFKAP-WXHSDQCUSA-N 0.000 description 1
229950001300 zofenoprilat Drugs 0.000 description 1
229950001346 zolimomab aritox Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Diabetes (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Obesity (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Steroid Compounds (AREA)

UA20041210110A 2002-07-05 2003-01-07 Diphenylacetidinon derivatives for treatment of disordered lipid metabolism, method of production thereof(variants), pharmaceutical composition UA78564C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0215579.4A GB0215579D0 (en)	2002-07-05	2002-07-05	Chemical compounds
PCT/GB2003/002811 WO2004005247A1 (en)	2002-07-05	2003-07-01	Diphenylazetidinone derivatives for treating disorders of the lipid metabolism

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Publication Number	Publication Date
UA78564C2 true UA78564C2 (en)	2007-04-10

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UA20041210110A UA78564C2 (en)	2002-07-05	2003-01-07	Diphenylacetidinon derivatives for treatment of disordered lipid metabolism, method of production thereof(variants), pharmaceutical composition

Country Status (21)

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US (1)	US7470678B2 (is)
EP (1)	EP1521742A1 (is)
JP (1)	JP2006501184A (is)
CN (2)	CN100528842C (is)
AR (1)	AR041185A1 (is)
BR (1)	BR0312280A (is)
CA (1)	CA2491789A1 (is)
GB (1)	GB0215579D0 (is)
IL (1)	IL165820A0 (is)
IS (1)	IS7648A (is)
MX (1)	MXPA04012936A (is)
NO (1)	NO20050016L (is)
NZ (1)	NZ537124A (is)
PL (1)	PL374725A1 (is)
RU (2)	RU2333199C2 (is)
SA (1)	SA02230379B1 (is)
TW (1)	TW200404058A (is)
UA (1)	UA78564C2 (is)
UY (1)	UY27882A1 (is)
WO (1)	WO2004005247A1 (is)
ZA (1)	ZA200410340B (is)

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2002
- 2002-07-05 GB GBGB0215579.4A patent/GB0215579D0/en not_active Ceased
- 2002-10-14 SA SA2230379A patent/SA02230379B1/ar unknown
2003
- 2003-01-07 UA UA20041210110A patent/UA78564C2/uk unknown
- 2003-06-30 TW TW092117830A patent/TW200404058A/zh unknown
- 2003-07-01 US US10/519,897 patent/US7470678B2/en not_active Expired - Fee Related
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- 2003-07-01 EP EP03762763A patent/EP1521742A1/en not_active Withdrawn
- 2003-07-01 WO PCT/GB2003/002811 patent/WO2004005247A1/en not_active Ceased
- 2003-07-01 BR BR0312280-8A patent/BR0312280A/pt not_active IP Right Cessation
- 2003-07-01 JP JP2004518920A patent/JP2006501184A/ja active Pending
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- 2003-07-01 CA CA002491789A patent/CA2491789A1/en not_active Abandoned
- 2003-07-01 CN CNA2007101050883A patent/CN101058556A/zh active Pending
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2004
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2005
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Publication number	Publication date
UY27882A1 (es)	2004-02-27
AR041185A1 (es)	2005-05-04
NO20050016L (no)	2005-03-01
IS7648A (is)	2005-01-13
CN101058556A (zh)	2007-10-24
CN100528842C (zh)	2009-08-19
PL374725A1 (en)	2005-10-31
US20050239766A1 (en)	2005-10-27
US7470678B2 (en)	2008-12-30
RU2008107146A (ru)	2009-09-10
SA02230379B1 (ar)	2008-09-02
ZA200410340B (en)	2005-10-20
TW200404058A (en)	2004-03-16
BR0312280A (pt)	2005-04-12
JP2006501184A (ja)	2006-01-12
CA2491789A1 (en)	2004-01-15
RU2333199C2 (ru)	2008-09-10
NZ537124A (en)	2008-03-28
IL165820A0 (en)	2006-01-15
RU2004137279A (ru)	2005-09-10
MXPA04012936A (es)	2005-05-16
WO2004005247A1 (en)	2004-01-15
AU2003242850A1 (en)	2004-01-23
GB0215579D0 (en)	2002-08-14
EP1521742A1 (en)	2005-04-13
CN1665783A (zh)	2005-09-07

Publication	Publication Date	Title
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US20070142304A1 (en)	2007-06-21	Diphenylazetidinone derivatives possessing chloesterol absorption inhibitory activity
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JP4688819B2 (ja)	2011-05-25	コレステロール吸収阻害活性を有するジフェニルアゼチジノン誘導体
US7863265B2 (en)	2011-01-04	2-azetidinone derivatives and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia
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JP2008546769A (ja)	2008-12-25	高脂血症状態の治療に有用な新規な２−アゼチジノン誘導体類
KR20080033265A (ko)	2008-04-16	고지혈성 병태의 치료를 위한 콜레스테롤 흡수억제제로서의 신규한 2-아제티디논 유도체
US20100152156A1 (en)	2010-06-17	2-Azetidinone Derivatives For The Treatment Of Hyperlipidaemic Diseases
AU2003242850B2 (en)	2007-05-03	Diphenylazetidinone derivatives for treating disorders of the lipid metabolism
KR20050023393A (ko)	2005-03-09	지질 대사 장애 치료용 디페닐아제티디논 유도체