JP2005502600A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
- Authority
- 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.)
- Pending
Links
- 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
- OAWYMJZHSVRNJN-UHFFFAOYSA-N 3-[4-[2-[2-(4-butoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-2-(phenylmethoxymethyl)phenyl]propanoic acid Chemical compound C1=CC(OCCCC)=CC=C1C1=NC(CCOC=2C=C(COCC=3C=CC=CC=3)C(CCC(O)=O)=CC=2)=C(C)O1 OAWYMJZHSVRNJN-UHFFFAOYSA-N 0.000 description 1
- KVYFJRYIBOTCAM-UHFFFAOYSA-N 3-[4-[2-[5-methyl-2-(3-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]-2-(phenylmethoxymethyl)phenyl]propanoic acid Chemical compound CC=1OC(C=2C=C(C=CC=2)C=2C=CC=CC=2)=NC=1CCOC(C=1)=CC=C(CCC(O)=O)C=1COCC1=CC=CC=C1 KVYFJRYIBOTCAM-UHFFFAOYSA-N 0.000 description 1
- IQUKHHMDOOYEQK-UHFFFAOYSA-N 3-[4-[2-[5-methyl-2-(4-phenoxyphenyl)-1,3-oxazol-4-yl]ethoxy]-2-(phenylmethoxymethyl)phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=NC=1CCOC(C=1)=CC=C(CCC(O)=O)C=1COCC1=CC=CC=C1 IQUKHHMDOOYEQK-UHFFFAOYSA-N 0.000 description 1
- UUAGEDLXJSERQQ-UHFFFAOYSA-N 3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]-2-(phenylmethoxymethyl)phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=NC=1CCOC(C=1)=CC=C(CCC(O)=O)C=1COCC1=CC=CC=C1 UUAGEDLXJSERQQ-UHFFFAOYSA-N 0.000 description 1
- UCCUTWODONOYOD-UHFFFAOYSA-N 3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]-2-(phenylmethoxymethyl)phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC(=CC=2)C(F)(F)F)=NC=1CCOC(C=1)=CC=C(CCC(O)=O)C=1COCC1=CC=CC=C1 UCCUTWODONOYOD-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 1
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229940113549 Cholesterol inhibitor Drugs 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- FTOJJOGFSZGXJW-UHFFFAOYSA-N ethyl 2-[4-hydroxy-2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(O)C=C1CNC(=O)OC(C)(C)C FTOJJOGFSZGXJW-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical class C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 description 1
- 239000002350 fibrinopeptide Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- 229940121380 ileal bile acid transporter inhibitor Drugs 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 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 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229950008446 melinamide Drugs 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229960004738 nicotinyl alcohol Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- 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
- 230000002335 preservative effect Effects 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
- 229960003912 probucol Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003335 secondary amines Chemical class 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
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- LMANIHDNHODFER-UHFFFAOYSA-N tert-butyl 3-[2-(bromomethyl)-4-[tert-butyl(diphenyl)silyl]oxyphenyl]propanoate Chemical compound C1=C(CBr)C(CCC(=O)OC(C)(C)C)=CC=C1O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 LMANIHDNHODFER-UHFFFAOYSA-N 0.000 description 1
- KFBYQEUIDJSOEJ-UHFFFAOYSA-N tert-butyl 3-[2-[(1,3-dioxoisoindol-2-yl)methyl]-4-hydroxyphenyl]propanoate Chemical compound CC(C)(C)OC(=O)CCC1=CC=C(O)C=C1CN1C(=O)C2=CC=CC=C2C1=O KFBYQEUIDJSOEJ-UHFFFAOYSA-N 0.000 description 1
- QZTVBUWFGUKEPQ-UHFFFAOYSA-N tert-butyl 3-[4-[tert-butyl(diphenyl)silyl]oxy-2-[[4-(trifluoromethyl)phenoxy]methyl]phenyl]propanoate Chemical compound C1=C(COC=2C=CC(=CC=2)C(F)(F)F)C(CCC(=O)OC(C)(C)C)=CC=C1O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 QZTVBUWFGUKEPQ-UHFFFAOYSA-N 0.000 description 1
- SGJAKZIZXOHBHM-UHFFFAOYSA-N tert-butyl 3-[4-hydroxy-2-[(propan-2-yloxycarbonylamino)methyl]phenyl]propanoate Chemical compound CC(C)OC(=O)NCC1=CC(O)=CC=C1CCC(=O)OC(C)(C)C SGJAKZIZXOHBHM-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-O tyraminium Chemical compound [NH3+]CCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-O 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29670101P | 2001-06-07 | 2001-06-07 | |
| PCT/US2002/015143 WO2002100403A1 (en) | 2001-06-07 | 2002-05-24 | Modulators of peroxisome proliferator activated receptors (ppar) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005502600A JP2005502600A (ja) | 2005-01-27 |
| JP2005502600A5 true JP2005502600A5 (cg-RX-API-DMAC7.html) | 2006-01-05 |
Family
ID=23143173
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003503224A Pending JP2005502600A (ja) | 2001-06-07 | 2002-05-24 | ペルオキシソーム増殖因子活性化受容体（ｐｐａｒ）のモジュレーター |
Country Status (22)
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ541950A (en) * | 2001-08-09 | 2007-02-23 | Ono Pharmaceutical Co | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
| US6867224B2 (en) | 2002-03-07 | 2005-03-15 | Warner-Lambert Company | 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 |
| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | 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 |
| EP1535915A4 (en) * | 2002-09-06 | 2005-10-05 | Takeda Pharmaceutical | FURANOIC OR THIOPHENE DERIVATIVES AND THEIR MEDICAL USE |
| US6653334B1 (en) * | 2002-12-27 | 2003-11-25 | Kowa Co., Ltd. | Benzoxazole compound and pharmaceutical composition containing the same |
| EP1583746A1 (en) | 2003-01-06 | 2005-10-12 | Eli Lilly And Company | A pyrazole derivative as ppar modulator |
| CA2515516A1 (en) * | 2003-02-07 | 2004-08-19 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid compounds |
| 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 |
| 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 |
| US7244763B2 (en) | 2003-04-17 | 2007-07-17 | Warner Lambert Company Llc | Compounds that modulate PPAR activity and methods of preparation |
| JP2007502815A (ja) * | 2003-08-20 | 2007-02-15 | イーライ リリー アンド カンパニー | Ｐｐａｒ調節因子 |
| BRPI0416238A (pt) * | 2003-11-05 | 2007-01-02 | Hoffmann La Roche | compostos, processo para a sua preparação, composição farmacêutica que compreende os mesmos, uso dos compostos e métodos para o tratamento e/ou a prevenção de doenças que são moduladas por ppar(delta) e/ou agonistas ppar(alfa) |
| 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 |
| WO2005095364A1 (ja) * | 2004-03-30 | 2005-10-13 | Daiichi Pharmaceutical Co. Ltd. | フェノキシ酢酸誘導体及びそれを用いた医薬 |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| 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 |
| US7932250B2 (en) | 2004-07-01 | 2011-04-26 | Daiichi Sankyo Company, Limited | Thienopyrazole derivative having PDE7 inhibitory activity |
| JP2007284352A (ja) * | 2004-08-05 | 2007-11-01 | Dai Ichi Seiyaku Co Ltd | ピラゾール誘導体 |
| SG170642A1 (en) * | 2004-11-03 | 2011-05-30 | Arena Pharm Inc | Gpr41 and modulators thereof for the treatment of insulin-related disorders |
| WO2006057448A1 (ja) * | 2004-11-26 | 2006-06-01 | Takeda Pharmaceutical Company Limited | 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 |
| EP1924546A1 (en) | 2005-09-14 | 2008-05-28 | 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 |
| 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 |
| JP5369257B2 (ja) * | 2006-02-15 | 2013-12-18 | アッヴィ・インコーポレイテッド | 新規なアセチル−ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害薬およびそれらの糖尿病、肥満および代謝症候群での使用 |
| 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 |
| WO2007147336A1 (fr) * | 2006-06-13 | 2007-12-27 | Shanghai Institue Of Materia Medica, Chinese Academy Of Sciences | Composés non nucléosidiques hétérocycliques, leur préparation, compositions pharmaceutiques, et leur utilisation en tant qu'agents antiviraux |
| CA2662242C (en) | 2006-09-07 | 2012-06-12 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| EP2064193A1 (en) | 2006-09-07 | 2009-06-03 | Amgen, Inc | Heterocyclic gpr40 modulators |
| ES2446419T3 (es) | 2007-04-16 | 2014-03-07 | Amgen, Inc | Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos |
| JP5591706B2 (ja) | 2007-10-10 | 2014-09-17 | アムジエン・インコーポレーテツド | 置換ビフェニルｇｐｒ４０調節因子 |
| JP2011515341A (ja) | 2008-03-06 | 2011-05-19 | アムジエン・インコーポレーテツド | 代謝障害の治療に有用な立体配座的に制限されたカルボン酸誘導体 |
| 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 |
| US9085570B2 (en) * | 2010-10-11 | 2015-07-21 | 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 |
| CN108368097B (zh) * | 2015-12-22 | 2021-03-09 | 住友化学株式会社 | 制备苯并噁唑化合物的方法 |
| 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 |
| WO2018216640A1 (ja) * | 2017-05-22 | 2018-11-29 | 小野薬品工業株式会社 | Ｅｐ４アンタゴニスト |
| 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 |
| ES2217392T3 (es) * | 1996-02-02 | 2004-11-01 | MERCK & CO., INC. | Agentes antidiabeticos. |
| CA2245529A1 (en) | 1996-02-02 | 1997-08-07 | Soumya P. Sahoo | Antidiabetic agents |
| GB9604242D0 (en) | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| KR100620337B1 (ko) | 1998-03-10 | 2006-09-13 | 오노 야꾸힝 고교 가부시키가이샤 | 카르복실산 유도체와 그 유도체를 유효 성분으로서함유하는 약제 |
| MXPA02003123A (es) | 1999-06-25 | 2003-08-20 | Inst For Pharm Discovery Inc | Acidos fenoxiaceticos substituidos. |
| CA2382966A1 (en) * | 1999-08-27 | 2001-03-08 | Eli Lilly And Company | Biaryl-oxa(thia)zole derivatives and their use as ppars modulators |
| 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、 |
| WO2002018355A1 (en) | 2000-08-23 | 2002-03-07 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
| MXPA03001610A (es) | 2000-08-23 | 2003-09-10 | Lilly Co Eli | Derivados de acido oxazolil-arilpropionico y su uso como agonistas de los receptores activados por proliferadores de peroxisomas. |
| NZ529351A (en) | 2001-06-07 | 2006-01-27 | Lilly Co Eli | Modulators of peroxisome proliferator activated receptors |
-
2002
- 2002-05-24 KR KR10-2003-7016048A patent/KR20040030658A/ko not_active Withdrawn
- 2002-05-24 EA EA200400011A patent/EA200400011A1/ru unknown
- 2002-05-24 WO PCT/US2002/015143 patent/WO2002100403A1/en not_active Ceased
- 2002-05-24 AT AT02746380T patent/ATE345128T1/de not_active IP Right Cessation
- 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 US US10/477,405 patent/US7282501B2/en not_active Expired - Fee Related
- 2002-05-24 ES ES02746380T patent/ES2275887T3/es not_active Expired - Lifetime
- 2002-05-24 MX MXPA03010903A patent/MXPA03010903A/es unknown
- 2002-05-24 DE DE60216094T patent/DE60216094T2/de not_active Expired - Fee Related
- 2002-05-24 CZ CZ20033328A patent/CZ20033328A3/cs unknown
- 2002-05-24 HR HR20031002A patent/HRP20031002A2/hr not_active Application Discontinuation
- 2002-05-24 IL IL15900202A patent/IL159002A0/xx unknown
- 2002-05-24 HU HU0400268A patent/HUP0400268A2/hu unknown
- 2002-05-24 SK SK1492-2003A patent/SK14922003A3/sk unknown
- 2002-05-24 PL PL02367077A patent/PL367077A1/xx not_active Application Discontinuation
- 2002-05-24 BR BR0210167-0A patent/BR0210167A/pt not_active IP Right Cessation
- 2002-05-24 CN CNA028154533A patent/CN1578659A/zh active Pending
- 2002-05-24 JP JP2003503224A patent/JP2005502600A/ja active Pending
-
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
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005502600A5 (cg-RX-API-DMAC7.html) | ||
| KR100706735B1 (ko) | ｈＰＰＡＲ 알파 활성제로서 치환된 옥사졸 및 티아졸유도체 | |
| US7465804B2 (en) | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders | |
| US7037914B2 (en) | Carboxylic acid derivative and a pharmaceutical composition containing the derivative as active ingredient | |
| AU2016228191B2 (en) | Synergistic compositions | |
| RU2419624C2 (ru) | Сульфонамидные производные как активаторы гликокиназы, применимые для лечения диабета типа 2 | |
| JP2006500384A5 (cg-RX-API-DMAC7.html) | ||
| ZA200100983B (en) | Substituted oxazoles and thiazoles derivatives as hPPAR gamma and hPPAR alpha activators. | |
| JP2004532266A (ja) | 心血管系疾患の治療に有用なチアゾールまたはオキサゾール誘導体 | |
| ZA200410061B (en) | Phenylalkanoic acid and phenyloxyalkanoic acid derivatives as hPPAR acivators | |
| KR100718906B1 (ko) | 디히드로나프탈렌 유도체 화합물 및 이 화합물을 유효성분으로 하는 약제 | |
| RU2005109163A (ru) | НОВЫЕ СОЕДИНЕНИЯ 2-АРИЛТИАЗОЛА В КАЧЕСТВЕ АГОНИСТОВ PPARα И PPARγ | |
| RU2005110921A (ru) | N-замещенные 1н-индол-5-пропионовые кислоты в качестве предшественников агонистов, используемых для лечения диабета | |
| KR100859591B1 (ko) | Ｈｐｐａｒ-알파 수용체의 옥사졸/티아졸-유도체 활성제 | |
| KR20060128921A (ko) | 항당뇨병성 옥사졸리딘디온 및 티아졸리딘디온 | |
| ES2390053T3 (es) | Derivado de ácido fenilacético, procedimiento para producir el mismo y uso | |
| KR100806004B1 (ko) | 선택적 페록시좀 증식제 활성화 수용체 조절제 | |
| JP2009500355A (ja) | 抗糖尿病性オキサゾリジンジオン及びチアゾリジンジオン | |
| ZA200204241B (en) | Substituted oxazoles and thiazoles derivatives as HPPAR Alpha Activators. | |
| JP2004026679A (ja) | ジヒドロナフタレン誘導体 |