KR20050014013A - 인슐린 내성의 치료를 위한 오르토-치환 벤조산 유도체 - Google Patents
인슐린 내성의 치료를 위한 오르토-치환 벤조산 유도체Info
- Publication number
- KR20050014013A KR20050014013A KR10-2004-7020670A KR20047020670A KR20050014013A KR 20050014013 A KR20050014013 A KR 20050014013A KR 20047020670 A KR20047020670 A KR 20047020670A KR 20050014013 A KR20050014013 A KR 20050014013A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- amino
- benzoic acid
- phenoxy
- oxopropyl
- Prior art date
- 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.)
- Withdrawn
Links
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 22
- 206010022489 Insulin Resistance Diseases 0.000 title claims abstract description 13
- 150000001558 benzoic acid derivatives Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 150000003839 salts Chemical class 0.000 claims abstract description 63
- 239000000651 prodrug Substances 0.000 claims abstract description 39
- 229940002612 prodrug Drugs 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 83
- -1 carboxyl hydroxyl Chemical group 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 8
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- RBCHSXQOPLPDHL-UHFFFAOYSA-N 2-[[4-[2-[ethyl-[(2-fluorophenyl)methyl]amino]-2-oxoethyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CC)CC1=CC=CC=C1F RBCHSXQOPLPDHL-UHFFFAOYSA-N 0.000 claims description 6
- WUEKSVVLDXBNSF-UHFFFAOYSA-N 2-[[4-[3-[(2,4-difluorophenyl)methyl-heptylamino]-3-oxopropyl]phenyl]sulfanylmethyl]benzoic acid Chemical compound C=1C=C(SCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCCCCC)CC1=CC=C(F)C=C1F WUEKSVVLDXBNSF-UHFFFAOYSA-N 0.000 claims description 6
- CKPOVXTWCZIWNQ-UHFFFAOYSA-N 2-[[4-[3-[(2,4-difluorophenyl)methyl-propylamino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCC)CC1=CC=C(F)C=C1F CKPOVXTWCZIWNQ-UHFFFAOYSA-N 0.000 claims description 6
- FHSYYHSGFQTOOS-UHFFFAOYSA-N 2-[[4-[3-[ethyl-[(2-fluorophenyl)methyl]amino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CC)CC1=CC=CC=C1F FHSYYHSGFQTOOS-UHFFFAOYSA-N 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- ZSECWGHWRUMBCP-UHFFFAOYSA-N 2-[[3-[2-[(2,4-difluorophenyl)methyl-heptylamino]-2-oxoethyl]phenyl]sulfanylmethyl]benzoic acid Chemical compound C=1C=CC(SCC=2C(=CC=CC=2)C(O)=O)=CC=1CC(=O)N(CCCCCCC)CC1=CC=C(F)C=C1F ZSECWGHWRUMBCP-UHFFFAOYSA-N 0.000 claims description 5
- AVLMOQWYTWOYRH-UHFFFAOYSA-N 2-[[4-[2-[(2,4-difluorophenyl)methyl-heptylamino]-2-oxoethyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CCCCCCC)CC1=CC=C(F)C=C1F AVLMOQWYTWOYRH-UHFFFAOYSA-N 0.000 claims description 5
- GGXHKHVHQONVSY-UHFFFAOYSA-N 2-[[4-[2-[(2,4-difluorophenyl)methyl-heptylamino]-2-oxoethyl]phenyl]sulfanylmethyl]benzoic acid Chemical compound C=1C=C(SCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CCCCCCC)CC1=CC=C(F)C=C1F GGXHKHVHQONVSY-UHFFFAOYSA-N 0.000 claims description 5
- CGAJIYOGBDNFEP-UHFFFAOYSA-N 2-[[4-[2-[(4-chlorophenyl)methyl-ethylamino]-2-oxoethyl]phenyl]sulfanylmethyl]benzoic acid Chemical compound C=1C=C(SCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CC)CC1=CC=C(Cl)C=C1 CGAJIYOGBDNFEP-UHFFFAOYSA-N 0.000 claims description 5
- ODDKTPKGWSSZGR-UHFFFAOYSA-N 2-[[4-[2-[benzyl(hexyl)amino]-2-oxoethyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CCCCCC)CC1=CC=CC=C1 ODDKTPKGWSSZGR-UHFFFAOYSA-N 0.000 claims description 5
- XGLUFCRYDGBRPS-UHFFFAOYSA-N 2-[[4-[2-[ethyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoethyl]phenyl]sulfanylmethyl]benzoic acid Chemical compound C=1C=C(SCC=2C(=CC=CC=2)C(O)=O)C=CC=1CC(=O)N(CC)CC1=CC=C(C(F)(F)F)C=C1 XGLUFCRYDGBRPS-UHFFFAOYSA-N 0.000 claims description 5
- NKKUNRCSUULMIN-UHFFFAOYSA-N 2-[[4-[3-[(2,3-dimethoxyphenyl)methyl-heptylamino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCCCCC)CC1=CC=CC(OC)=C1OC NKKUNRCSUULMIN-UHFFFAOYSA-N 0.000 claims description 5
- DFLAODURXLNIJS-UHFFFAOYSA-N 2-[[4-[3-[(2,4-difluorophenyl)methyl-heptylamino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCCCCC)CC1=CC=C(F)C=C1F DFLAODURXLNIJS-UHFFFAOYSA-N 0.000 claims description 5
- FRLGWPVOKQSMFS-UHFFFAOYSA-N 2-[[4-[3-[3-ethoxypropyl-[(4-propan-2-ylphenyl)methyl]amino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCOCC)CC1=CC=C(C(C)C)C=C1 FRLGWPVOKQSMFS-UHFFFAOYSA-N 0.000 claims description 5
- BRAPPIAYKRVJSD-UHFFFAOYSA-N 2-[[4-[3-[benzyl(hexyl)amino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCCCC)CC1=CC=CC=C1 BRAPPIAYKRVJSD-UHFFFAOYSA-N 0.000 claims description 5
- UTMNUBXVBHWRSP-UHFFFAOYSA-N 2-[[4-[3-[butyl-[(2,3-dimethoxyphenyl)methyl]amino]-3-oxopropyl]phenoxy]methyl]benzoic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C(O)=O)C=CC=1CCC(=O)N(CCCC)CC1=CC=CC(OC)=C1OC UTMNUBXVBHWRSP-UHFFFAOYSA-N 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 238000002648 combination therapy Methods 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000012351 deprotecting agent Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 208
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- 239000012453 solvate Substances 0.000 description 55
- 238000005481 NMR spectroscopy Methods 0.000 description 52
- 238000001704 evaporation Methods 0.000 description 43
- 230000008020 evaporation Effects 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 42
- 239000002904 solvent Substances 0.000 description 40
- 239000000047 product Substances 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 239000000872 buffer Substances 0.000 description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000012043 crude product Substances 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 13
- 239000005695 Ammonium acetate Substances 0.000 description 13
- 235000019257 ammonium acetate Nutrition 0.000 description 13
- 229940043376 ammonium acetate Drugs 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- QKASDIPENBEWBU-UHFFFAOYSA-N methyl 2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CBr QKASDIPENBEWBU-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 7
- 102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 description 7
- 101710156096 Ileal sodium/bile acid cotransporter Proteins 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
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- 239000012317 TBTU Substances 0.000 description 6
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
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- 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 description 1
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- 230000002265 prevention Effects 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 229960003042 quinapril hydrochloride Drugs 0.000 description 1
- IBBLRJGOOANPTQ-JKVLGAQCSA-N quinapril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 IBBLRJGOOANPTQ-JKVLGAQCSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
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- 102000005962 receptors Human genes 0.000 description 1
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- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 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 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229950010186 teprotide Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000001835 viscera Anatomy 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
- 229950001300 zofenoprilat Drugs 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201935-4 | 2002-06-20 | ||
| SE0201935A SE0201935D0 (sv) | 2002-06-20 | 2002-06-20 | Therapeutic agents |
| SE0203826A SE0203826D0 (sv) | 2002-12-20 | 2002-12-20 | Therapeutic agents |
| SE0203826-3 | 2002-12-20 | ||
| PCT/GB2003/002584 WO2004000790A1 (en) | 2002-06-20 | 2003-06-17 | Ortho-substituted benzoic acid derivatives for the treatment of insulin resistance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20050014013A true KR20050014013A (ko) | 2005-02-05 |
Family
ID=30002442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7020670A Withdrawn KR20050014013A (ko) | 2002-06-20 | 2003-06-17 | 인슐린 내성의 치료를 위한 오르토-치환 벤조산 유도체 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7355069B2 (https=) |
| EP (1) | EP1517883B8 (https=) |
| JP (2) | JP3782818B2 (https=) |
| KR (1) | KR20050014013A (https=) |
| CN (1) | CN1319938C (https=) |
| AR (1) | AR039713A1 (https=) |
| AT (1) | ATE386013T1 (https=) |
| AU (1) | AU2003240099B2 (https=) |
| BR (1) | BR0311932A (https=) |
| CA (1) | CA2489834C (https=) |
| DE (1) | DE60319084T2 (https=) |
| DK (1) | DK1517883T3 (https=) |
| ES (1) | ES2299702T3 (https=) |
| IL (1) | IL165671A0 (https=) |
| IS (1) | IS7627A (https=) |
| MX (1) | MXPA04012686A (https=) |
| NO (1) | NO20045353L (https=) |
| PL (1) | PL375074A1 (https=) |
| PT (1) | PT1517883E (https=) |
| RU (1) | RU2004137094A (https=) |
| TW (1) | TWI282784B (https=) |
| WO (1) | WO2004000790A1 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6262118B1 (en) * | 1999-06-04 | 2001-07-17 | Metabolex, Inc. | Use of (-) (3-trihalomethylphenoxy) (4-halophenyl) acetic acid derivatives for treatment of insulin resistance, type 2 diabetes and hyperlipidemia |
| US7576131B2 (en) * | 1999-06-04 | 2009-08-18 | Metabolex, Inc. | Use of (-) (3-trihalomethylphenoxy) (4-halophenyl) acetic acid derivatives for treatment of insulin resistance, type 2 diabetes, hyperlipidemia and hyperuricemia |
| SE0104333D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| FR2875805B1 (fr) * | 2004-09-27 | 2006-12-29 | Genfit S A | Composes derives de n-(benzyl) phenylacetamide substitues, preparation et utilisations |
| GB0522433D0 (en) * | 2005-11-03 | 2005-12-14 | Astrazeneca Ab | Therapeutic agents |
| GB0522431D0 (en) * | 2005-11-03 | 2005-12-14 | Astrazeneca Ab | Chemical process |
Family Cites Families (34)
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| DK148576A (da) | 1975-04-18 | 1976-10-19 | Boehringer Mannheim Gmbh | Fenylalkankarbonsyrederivater og fremgangsmade til deres fremstilling |
| DE19615263A1 (de) | 1996-04-18 | 1997-10-23 | Bayer Ag | Benzyloxy-substituierte Phenylglycinolamide |
| BR9814087A (pt) | 1997-10-17 | 2000-10-03 | Aventis Pharm Prod Inc | Processos para mediar a atividade do receptor de ppar-gama, e para tratar uma condição fisiológica em um paciente |
| EP1040108B1 (en) | 1997-12-19 | 2004-02-25 | Schering Aktiengesellschaft | Ortho-anthranilamide derivatives as anti-coagulants |
| SE9801992D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
| GB9822473D0 (en) | 1998-10-16 | 1998-12-09 | Glaxo Group Ltd | Chemical compounds |
| NZ515086A (en) | 1999-04-28 | 2003-10-31 | Aventis Pharma Gmbh | Di-aryl acid derivatives as PPAR receptor ligands |
| EP1177176B1 (en) | 1999-04-28 | 2006-04-19 | Aventis Pharma Deutschland GmbH | Tri-aryl acid derivatives as ppar receptor ligands |
| JP4618845B2 (ja) | 1999-06-09 | 2011-01-26 | 杏林製薬株式会社 | ヒトペルオキシゾーム増殖薬活性化受容体（ＰＰＡＲ）αアゴニストとしての置換フェニルプロピオン酸誘導体 |
| GB9919411D0 (en) | 1999-08-18 | 1999-10-20 | Zeneca Ltd | Chemical compounds |
| SE0000772D0 (sv) | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | Chemical compounds |
| US6509374B2 (en) | 2000-04-17 | 2003-01-21 | Novo Nordisk A/S | Compounds, their preparation and use |
| SE0003766D0 (sv) | 2000-10-18 | 2000-10-18 | Astrazeneca Ab | Novel formulation |
| EG26979A (en) | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| GB0116955D0 (en) | 2001-07-11 | 2001-09-05 | Syngenta Ltd | Weed control process |
| GB0121337D0 (en) | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| TWI331143B (en) | 2001-09-08 | 2010-10-01 | Astrazeneca Uk Ltd | Benzothiadiazepine derivatives, process for preparing them, and pharmaceutical composition comprising them |
| SE0104333D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| GB0229931D0 (en) | 2002-12-21 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| SE0104334D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| GB0209467D0 (en) | 2002-04-25 | 2002-06-05 | Astrazeneca Ab | Chemical compounds |
| GB0213669D0 (en) | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| US7351858B2 (en) | 2002-06-20 | 2008-04-01 | Astrazeneca Ab | Ortho-substituted benzoic acid derivatives for the treatment of insulin resistance |
| SE0201936D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | Therapeutic agents |
| SE0201937D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | Therapeutic agents |
| GB0314130D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| GB0314136D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| GB0314131D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| GB0314129D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| GB0314075D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| GB0314078D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
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2003
- 2003-06-17 PL PL03375074A patent/PL375074A1/xx not_active Application Discontinuation
- 2003-06-17 JP JP2004515007A patent/JP3782818B2/ja not_active Expired - Lifetime
- 2003-06-17 CN CNB038194740A patent/CN1319938C/zh not_active Expired - Fee Related
- 2003-06-17 KR KR10-2004-7020670A patent/KR20050014013A/ko not_active Withdrawn
- 2003-06-17 CA CA002489834A patent/CA2489834C/en not_active Expired - Fee Related
- 2003-06-17 BR BR0311932-7A patent/BR0311932A/pt not_active IP Right Cessation
- 2003-06-17 DE DE60319084T patent/DE60319084T2/de not_active Expired - Lifetime
- 2003-06-17 TW TW092116378A patent/TWI282784B/zh not_active IP Right Cessation
- 2003-06-17 US US10/518,007 patent/US7355069B2/en not_active Expired - Fee Related
- 2003-06-17 MX MXPA04012686A patent/MXPA04012686A/es not_active Application Discontinuation
- 2003-06-17 EP EP03732713A patent/EP1517883B8/en not_active Expired - Lifetime
- 2003-06-17 ES ES03732713T patent/ES2299702T3/es not_active Expired - Lifetime
- 2003-06-17 WO PCT/GB2003/002584 patent/WO2004000790A1/en not_active Ceased
- 2003-06-17 RU RU2004137094/04A patent/RU2004137094A/ru not_active Application Discontinuation
- 2003-06-17 AT AT03732713T patent/ATE386013T1/de not_active IP Right Cessation
- 2003-06-17 AU AU2003240099A patent/AU2003240099B2/en not_active Ceased
- 2003-06-17 DK DK03732713T patent/DK1517883T3/da active
- 2003-06-17 PT PT03732713T patent/PT1517883E/pt unknown
- 2003-06-20 AR ARP030102197A patent/AR039713A1/es not_active Application Discontinuation
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2004
- 2004-12-07 NO NO20045353A patent/NO20045353L/no not_active Application Discontinuation
- 2004-12-09 IL IL16567104A patent/IL165671A0/xx unknown
-
2005
- 2005-01-05 IS IS7627A patent/IS7627A/is unknown
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2006
- 2006-01-27 JP JP2006019068A patent/JP2006182782A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20050256198A1 (en) | 2005-11-17 |
| AU2003240099A1 (en) | 2004-01-06 |
| RU2004137094A (ru) | 2005-08-10 |
| ATE386013T1 (de) | 2008-03-15 |
| TWI282784B (en) | 2007-06-21 |
| IS7627A (is) | 2005-01-05 |
| DK1517883T3 (da) | 2008-05-26 |
| MXPA04012686A (es) | 2005-03-23 |
| DE60319084D1 (de) | 2008-03-27 |
| CA2489834C (en) | 2006-10-03 |
| CA2489834A1 (en) | 2003-12-31 |
| DE60319084T2 (de) | 2009-01-29 |
| PL375074A1 (en) | 2005-11-14 |
| TW200409747A (en) | 2004-06-16 |
| US7355069B2 (en) | 2008-04-08 |
| HK1073838A1 (en) | 2005-10-21 |
| EP1517883A1 (en) | 2005-03-30 |
| CN1675171A (zh) | 2005-09-28 |
| ES2299702T3 (es) | 2008-06-01 |
| AR039713A1 (es) | 2005-03-09 |
| JP3782818B2 (ja) | 2006-06-07 |
| AU2003240099B2 (en) | 2007-02-01 |
| EP1517883B1 (en) | 2008-02-13 |
| PT1517883E (pt) | 2008-04-21 |
| IL165671A0 (en) | 2006-01-15 |
| BR0311932A (pt) | 2005-03-22 |
| JP2006182782A (ja) | 2006-07-13 |
| NO20045353L (no) | 2005-01-20 |
| JP2005529970A (ja) | 2005-10-06 |
| EP1517883B8 (en) | 2008-05-21 |
| WO2004000790A1 (en) | 2003-12-31 |
| CN1319938C (zh) | 2007-06-06 |
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