JP2005502600A5 - - Google Patents
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- JP2005502600A5 JP2005502600A5 JP2003503224A JP2003503224A JP2005502600A5 JP 2005502600 A5 JP2005502600 A5 JP 2005502600A5 JP 2003503224 A JP2003503224 A JP 2003503224A JP 2003503224 A JP2003503224 A JP 2003503224A JP 2005502600 A5 JP2005502600 A5 JP 2005502600A5
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- JP
- Japan
- Prior art keywords
- alkyl
- compound
- aryl
- heteroaryl
- structural formula
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 32
- -1 C (O) -aryl Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 20
- 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 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 8
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 8
- 102000004877 Insulin Human genes 0.000 claims description 7
- 108090001061 Insulin Proteins 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 7
- 229940125396 insulin Drugs 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 6
- 229940123208 Biguanide Drugs 0.000 claims description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims description 6
- 229940100389 Sulfonylurea Drugs 0.000 claims description 6
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 6
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 6
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 5
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 5
- 229940122199 Insulin secretagogue Drugs 0.000 claims description 5
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 5
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 239000002404 acyltransferase inhibitor Substances 0.000 claims description 5
- 230000003579 anti-obesity Effects 0.000 claims description 5
- 239000003529 anticholesteremic agent Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
- 239000003524 antilipemic agent Substances 0.000 claims 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 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 229940088594 vitamin Drugs 0.000 claims description 4
- 239000011782 vitamin Substances 0.000 claims description 4
- 235000013343 vitamin Nutrition 0.000 claims description 4
- 229930003231 vitamin Natural products 0.000 claims description 4
- 229940123324 Acyltransferase inhibitor Drugs 0.000 claims description 3
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
- 208000032841 Bulimia Diseases 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 3
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 claims description 3
- 108010054082 Sterol O-acyltransferase Proteins 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000003028 elevating effect Effects 0.000 claims description 3
- 229940125753 fibrate Drugs 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 15
- 125000003118 aryl group Chemical group 0.000 claims 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 7
- 125000004104 aryloxy group Chemical group 0.000 claims 7
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 241000124008 Mammalia Species 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 239000000470 constituent Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 239000003614 peroxisome proliferator Substances 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 150000003722 vitamin derivatives Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000010561 standard procedure Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001274216 Naso Species 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000010931 ester hydrolysis Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- QGNITQXBLBMGSS-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl 4-methylbenzenesulfonate Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOS(=O)(=O)C1=CC=C(C)C=C1 QGNITQXBLBMGSS-UHFFFAOYSA-N 0.000 description 2
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 229950002375 englitazone Drugs 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- OVPLZYJGTGDFNB-UHFFFAOYSA-N propan-2-yl carbamate Chemical compound CC(C)OC(N)=O OVPLZYJGTGDFNB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- 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 1
- RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 1
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 1
- 0 *c1c(CCOc2cc(COCc3ccccc3)c(CCC(O)=O)cc2)nc(-c2ccc(C(F)(F)F)cc2)[o]1 Chemical compound *c1c(CCOc2cc(COCc3ccccc3)c(CCC(O)=O)cc2)nc(-c2ccc(C(F)(F)F)cc2)[o]1 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- VUUGKSBHZXJBFD-UHFFFAOYSA-N 2-(5-methyl-2-naphthalen-2-yl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(C=2C=C3C=CC=CC3=CC=2)=N1 VUUGKSBHZXJBFD-UHFFFAOYSA-N 0.000 description 1
- GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
- AGGPLXNWVAGIBW-UHFFFAOYSA-N 2-methyl-2-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenoxy]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(OC(C)(C)C(O)=O)C(CNC(=O)OC(C)(C)C)=C1 AGGPLXNWVAGIBW-UHFFFAOYSA-N 0.000 description 1
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| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | Compounds that modulate PPAR activity and methods of preparation |
| US20030207924A1 (en) * | 2002-03-07 | 2003-11-06 | Xue-Min Cheng | Compounds that modulate PPAR activity and methods of preparation |
| US6867224B2 (en) | 2002-03-07 | 2005-03-15 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods of preparation |
| US6716842B2 (en) * | 2002-04-05 | 2004-04-06 | Warner-Lambert Company, Llc | Antidiabetic agents |
| US6875780B2 (en) | 2002-04-05 | 2005-04-05 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
| JP2005035966A (ja) * | 2002-09-06 | 2005-02-10 | Takeda Chem Ind Ltd | フランまたはチオフェン誘導体およびその医薬用途 |
| CA2497901A1 (en) * | 2002-09-06 | 2004-03-18 | Takeda Pharmaceutical Company Limited | Furan or thiophene derivative and medicinal use thereof |
| US6653334B1 (en) * | 2002-12-27 | 2003-11-25 | Kowa Co., Ltd. | Benzoxazole compound and pharmaceutical composition containing the same |
| WO2004063166A1 (en) * | 2003-01-06 | 2004-07-29 | Eli Lilly And Company | Heterocyclic ppar modulators |
| NZ541603A (en) * | 2003-02-07 | 2008-03-28 | Ono Pharmaceutical Co | Carbonyl phenyl propanoic acid derivative compounds |
| DE10308351A1 (de) * | 2003-02-27 | 2004-11-25 | Aventis Pharma Deutschland Gmbh | 1,3-substituierte Cycloalkylderivate mit sauren, meist heterocyclischen Gruppen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE10308355A1 (de) | 2003-02-27 | 2004-12-23 | Aventis Pharma Deutschland Gmbh | Aryl-cycloalkyl substituierte Alkansäurederivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
| US7244763B2 (en) | 2003-04-17 | 2007-07-17 | Warner Lambert Company Llc | Compounds that modulate PPAR activity and methods of preparation |
| EP1660428A1 (en) * | 2003-08-20 | 2006-05-31 | Eli Lilly And Company | Ppar modulators |
| MXPA06004642A (es) * | 2003-11-05 | 2006-06-27 | Hoffmann La Roche | Derivados de heteroaril como activadores de los receptores activados de proliferadores de peroxisoma (ppar). |
| DE10351859A1 (de) * | 2003-11-06 | 2005-06-09 | Beiersdorf Ag | Emulsionen mit zwei Verdickungsmitteln |
| BRPI0508098A (pt) | 2004-02-27 | 2007-07-17 | Amgen Inc | compostos, composições farmacêuticas e métodos para uso no tratamento de distúrbios metabólicos |
| JP2007223901A (ja) * | 2004-03-24 | 2007-09-06 | Takeda Chem Ind Ltd | 複素環化合物およびその用途 |
| US20070208021A1 (en) * | 2004-03-30 | 2007-09-06 | Daiichi Pharmaceutical Co., Ltd. | Phenoxyacetic Acid Derivatives and Drug Comprising The Same |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| CN100344618C (zh) | 2004-05-24 | 2007-10-24 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的N－芳丙烯酰基取代的酪氨酸衍生物 |
| CN100436430C (zh) * | 2004-05-24 | 2008-11-26 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的烷酰基取代的酪氨酸衍生物 |
| PT1775298E (pt) | 2004-07-01 | 2013-06-12 | Daiichi Sankyo Co Ltd | Derivado de tienopirazol com atividade inibidora da pde 7 |
| JP2007284352A (ja) * | 2004-08-05 | 2007-11-01 | Dai Ichi Seiyaku Co Ltd | ピラゾール誘導体 |
| CA2584224A1 (en) * | 2004-11-03 | 2006-05-18 | Arena Pharmaceuticals, Inc. | Gpr41 and modulators thereof for the treatment of insulin-related disorders |
| JPWO2006057448A1 (ja) * | 2004-11-26 | 2008-06-05 | 武田薬品工業株式会社 | アリールアルカン酸誘導体 |
| DE102004060227B3 (de) | 2004-12-15 | 2006-07-20 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung von Oxazolen durch Kondensation von aromatischen Aldehyden mit α-Ketoximen zu N-Oxiden und nachfolgende Reaktion mit aktivierten Säurederivaten |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| CA2621949A1 (en) | 2005-09-14 | 2007-03-22 | Amgen Inc. | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| JP2008303145A (ja) * | 2005-09-22 | 2008-12-18 | Takeda Chem Ind Ltd | Ｇｒｋ阻害剤からなる強心薬 |
| US8067607B2 (en) * | 2006-02-01 | 2011-11-29 | Merck Sharp & Dohme Corp. | Potassium channel inhibitors |
| EP1999119A2 (en) | 2006-02-15 | 2008-12-10 | Abbott Laboratories | Novel acetyl-coa carboxylase (acc) inhibitors and their use in diabetes, obesity and metabolic syndrome |
| CA2641766A1 (en) | 2006-02-15 | 2007-08-23 | Abbott Laboratories | Novel acetyl-coa carboxylase (acc) inhibitors and their use in diabetes, obesity and metabolic syndrome |
| CN101054372B (zh) * | 2006-04-11 | 2010-10-13 | 中国科学院上海药物研究所 | 嘧啶取代苯丙酸衍生化合物、其制法和在治疗多囊肾疾病中的用途 |
| US8653115B2 (en) * | 2006-06-13 | 2014-02-18 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | Heterocyclic non-nucleoside compounds, their preparation, pharmaceutical composition and their use as antiviral agents |
| US7714008B2 (en) | 2006-09-07 | 2010-05-11 | Amgen Inc. | Heterocyclic GPR40 modulators |
| US7687526B2 (en) | 2006-09-07 | 2010-03-30 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| EP2139843B1 (en) | 2007-04-16 | 2013-12-25 | Amgen, Inc | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators |
| EP2205548A1 (en) | 2007-10-10 | 2010-07-14 | Amgen, Inc | Substituted biphenyl gpr40 modulators |
| CA2716352C (en) | 2008-03-06 | 2013-05-28 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
| EP2358656B1 (en) | 2008-10-15 | 2014-01-01 | Amgen, Inc | Spirocyclic gpr40 modulators |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| WO2012051117A2 (en) * | 2010-10-11 | 2012-04-19 | The Board Of Trustees Of The Leland Stanford Junior University | Substituted benzamides and their uses |
| KR101942752B1 (ko) * | 2012-11-05 | 2019-01-28 | 주식회사 엘지화학 | Ｇｐｒ120 효능제로서의 티오아릴 유도체 |
| WO2016057322A1 (en) | 2014-10-08 | 2016-04-14 | Salk Institute For Biological Studies | Ppar agonists and methods of use thereof |
| US10188627B2 (en) | 2014-10-08 | 2019-01-29 | Mitobridge, Inc. | PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof |
| CN105237389B (zh) * | 2015-10-28 | 2017-09-15 | 成都丽凯手性技术有限公司 | 一种采用对香豆酸制备降血脂药环丙贝特的方法 |
| KR102627711B1 (ko) * | 2015-12-22 | 2024-01-22 | 수미토모 케미칼 컴퍼니 리미티드 | 벤즈옥사졸 화합물의 제조 방법 |
| WO2018011230A1 (en) * | 2016-07-13 | 2018-01-18 | Universite D'aix-Marseille | Peroxisome proliferator-activated receptor gamma agonists, method of preparation and uses thereof |
| JP6931456B2 (ja) * | 2017-04-03 | 2021-09-08 | 川崎化成工業株式会社 | ２−ハロアルコキシ−６−置換オキシナフタレン化合物及び２−ハロアルコキシ−６−置換オキシナフタレン化合物を含有する光重合増感剤 |
| US11479550B2 (en) * | 2017-05-22 | 2022-10-25 | Ono Pharmaceutical Co., Ltd. | EP4 antagonist |
| WO2021161218A1 (en) * | 2020-02-11 | 2021-08-19 | Inorbit Therapeutics Ab | Sulfinic acid and sulfonic acid compounds for use in modulating peroxisome proliferator-activated receptors |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5089514A (en) | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
| US5232945A (en) | 1992-07-20 | 1993-08-03 | Pfizer Inc. | 3-aryl-2-hydroxypropionic acid derivatives and analogs as antihypertensives |
| US5902726A (en) | 1994-12-23 | 1999-05-11 | Glaxo Wellcome Inc. | Activators of the nuclear orphan receptor peroxisome proliferator-activated receptor gamma |
| US6062509A (en) | 1994-12-23 | 2000-05-16 | Hexcel Corporation | Retrofit centerline luggage bin assemblies compatible with existing aircraft bin supports |
| CA2245529A1 (en) | 1996-02-02 | 1997-08-07 | Soumya P. Sahoo | Antidiabetic agents |
| DE69728267T2 (de) * | 1996-02-02 | 2005-02-24 | Merck & Co., Inc. | Antidiabetisches mittel |
| GB9604242D0 (en) | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| AU3275999A (en) | 1998-03-10 | 1999-09-27 | Ono Pharmaceutical Co. Ltd. | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
| IL147197A0 (en) | 1999-06-25 | 2002-08-14 | Inst For Pharm Discovery Inc | Substituted phenoxy acetic acids |
| US6417212B1 (en) * | 1999-08-27 | 2002-07-09 | Eli Lilly & Company | Modulators of peroxisome proliferator activated receptors |
| TWI262185B (en) | 1999-10-01 | 2006-09-21 | Eisai Co Ltd | Carboxylic acid derivatives having anti-hyperglycemia and anti-hyperlipemia action, and pharmaceutical composition containing the derivatives |
| JP4316787B2 (ja) | 2000-01-11 | 2009-08-19 | 壽製薬株式会社 | エーテル又はアミド誘導体、その製法並びにそれを含有する糖尿病治療剤、 |
| JP2004506722A (ja) * | 2000-08-23 | 2004-03-04 | イーライ・リリー・アンド・カンパニー | ペルオキシソーム増殖因子活性化受容体の調節方法 |
| WO2002018355A1 (en) | 2000-08-23 | 2002-03-07 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
| US7192982B2 (en) | 2001-06-07 | 2007-03-20 | Ligand Pharmaceuticals, Inc. | Modulators of peroxisome proliferator activated receptors |
-
2002
- 2002-05-24 BR BR0210167-0A patent/BR0210167A/pt not_active IP Right Cessation
- 2002-05-24 HR HR20031002A patent/HRP20031002A2/hr not_active Application Discontinuation
- 2002-05-24 ES ES02746380T patent/ES2275887T3/es not_active Expired - Lifetime
- 2002-05-24 HU HU0400268A patent/HUP0400268A2/hu unknown
- 2002-05-24 EA EA200400011A patent/EA200400011A1/ru unknown
- 2002-05-24 PL PL02367077A patent/PL367077A1/xx not_active Application Discontinuation
- 2002-05-24 IL IL15900202A patent/IL159002A0/xx unknown
- 2002-05-24 CZ CZ20033328A patent/CZ20033328A3/cs unknown
- 2002-05-24 KR KR10-2003-7016048A patent/KR20040030658A/ko not_active Withdrawn
- 2002-05-24 US US10/477,405 patent/US7282501B2/en not_active Expired - Fee Related
- 2002-05-24 SK SK1492-2003A patent/SK14922003A3/sk unknown
- 2002-05-24 CN CNA028154533A patent/CN1578659A/zh active Pending
- 2002-05-24 JP JP2003503224A patent/JP2005502600A/ja active Pending
- 2002-05-24 EP EP02746380A patent/EP1401434B1/en not_active Expired - Lifetime
- 2002-05-24 CA CA002448552A patent/CA2448552A1/en not_active Abandoned
- 2002-05-24 DE DE60216094T patent/DE60216094T2/de not_active Expired - Fee Related
- 2002-05-24 AT AT02746380T patent/ATE345128T1/de not_active IP Right Cessation
- 2002-05-24 MX MXPA03010903A patent/MXPA03010903A/es unknown
- 2002-05-24 WO PCT/US2002/015143 patent/WO2002100403A1/en not_active Ceased
-
2003
- 2003-11-20 ZA ZA200309059A patent/ZA200309059B/en unknown
- 2003-12-02 NO NO20035367A patent/NO20035367D0/no not_active Application Discontinuation
- 2003-12-05 EC EC2003004878A patent/ECSP034878A/es unknown
-
2007
- 2007-10-03 US US11/866,568 patent/US20080167310A1/en not_active Abandoned
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