NO326559B1 - Heterocykliske derivater og farmasoytiske midler inneholdende disse - Google Patents

Heterocykliske derivater og farmasoytiske midler inneholdende disse Download PDF

Info

Publication number: NO326559B1
Authority: NO; Norway
Prior art keywords: tetrahydroisoquinoline; carboxylic acid; ethoxy; methyl; alkyl
Prior art date: 2001-05-29

Application number

NO20035332A

Other languages

English (en)

Norwegian (no)

Other versions

NO20035332D0 (no

Inventor

Hideo Kobayashi

Satoru Azukizawa

Masayasu Kasai

Akihisa Yoshimi

Hiroaki Shirahase

Hiroshi Matsui

Original Assignee

Kyoto Pharma Ind

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

2001-05-29

Filing date

2003-11-28

Publication date

2009-01-12

2003-11-28 Application filed by Kyoto Pharma Ind filed Critical Kyoto Pharma Ind

2003-11-28 Publication of NO20035332D0 publication Critical patent/NO20035332D0/no

2009-01-12 Publication of NO326559B1 publication Critical patent/NO326559B1/no

Links

125000000623 heterocyclic group Chemical group 0.000 title claims description 39
239000008177 pharmaceutical agent Substances 0.000 title claims description 9
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 98
150000003839 salts Chemical class 0.000 claims description 46
125000000217 alkyl group Chemical group 0.000 claims description 45
239000003795 chemical substances by application Substances 0.000 claims description 35
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 25
206010022489 Insulin Resistance Diseases 0.000 claims description 22
BWKMGYQJPOAASG-VIFPVBQESA-N (3s)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CN[C@H](C(=O)O)CC2=C1 BWKMGYQJPOAASG-VIFPVBQESA-N 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 17
238000011321 prophylaxis Methods 0.000 claims description 17
229940124597 therapeutic agent Drugs 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 17
125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 16
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 15
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 15
206010012601 diabetes mellitus Diseases 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 13
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
208000002249 Diabetes Complications Diseases 0.000 claims description 10
206010012655 Diabetic complications Diseases 0.000 claims description 10
208000002705 Glucose Intolerance Diseases 0.000 claims description 9
206010018429 Glucose tolerance impaired Diseases 0.000 claims description 9
230000001404 mediated effect Effects 0.000 claims description 9
208000011580 syndromic disease Diseases 0.000 claims description 9
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 8
239000002260 anti-inflammatory agent Substances 0.000 claims description 8
229940121363 anti-inflammatory agent Drugs 0.000 claims description 8
239000000883 anti-obesity agent Substances 0.000 claims description 8
239000003524 antilipemic agent Substances 0.000 claims description 8
229940125710 antiobesity agent Drugs 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
239000003472 antidiabetic agent Substances 0.000 claims description 7
229940126904 hypoglycaemic agent Drugs 0.000 claims description 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 5
206010003210 Arteriosclerosis Diseases 0.000 claims description 4
208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
150000001875 compounds Chemical class 0.000 description 178
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
239000000203 mixture Substances 0.000 description 65
-1 7-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-phenyl-1,2,3,4-tetrahydroisoquinoline Chemical compound 0.000 description 64
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
238000006243 chemical reaction Methods 0.000 description 48
238000005160 1H NMR spectroscopy Methods 0.000 description 46
238000004519 manufacturing process Methods 0.000 description 46
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 38
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
238000005481 NMR spectroscopy Methods 0.000 description 23
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
239000011734 sodium Substances 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 19
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
238000012360 testing method Methods 0.000 description 18
210000004369 blood Anatomy 0.000 description 17
239000008280 blood Substances 0.000 description 17
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 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
239000002585 base Substances 0.000 description 16
239000008103 glucose Substances 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 11
241000700159 Rattus Species 0.000 description 10
239000013078 crystal Substances 0.000 description 10
238000001914 filtration Methods 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
230000000694 effects Effects 0.000 description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
238000000034 method Methods 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
241000699670 Mus sp. Species 0.000 description 8
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
230000002218 hypoglycaemic effect Effects 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
235000011181 potassium carbonates Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
230000037396 body weight Effects 0.000 description 6
239000007810 chemical reaction solvent Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
229920000609 methyl cellulose Polymers 0.000 description 6
239000001923 methylcellulose Substances 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
230000035484 reaction time Effects 0.000 description 6
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
229910000147 aluminium phosphate Inorganic materials 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
230000000055 hyoplipidemic effect Effects 0.000 description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
210000004185 liver Anatomy 0.000 description 5
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
SIRKPSSXHXSLMR-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 SIRKPSSXHXSLMR-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
150000008065 acid anhydrides Chemical class 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
210000000593 adipose tissue white Anatomy 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
210000003743 erythrocyte Anatomy 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
210000002216 heart Anatomy 0.000 description 4
238000005534 hematocrit Methods 0.000 description 4
239000002198 insoluble material Substances 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 4
235000020925 non fasting Nutrition 0.000 description 4
229910000073 phosphorus hydride Inorganic materials 0.000 description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 4
210000003462 vein Anatomy 0.000 description 4
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229920000084 Gum arabic Polymers 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
208000008589 Obesity Diseases 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
241000978776 Senegalia senegal Species 0.000 description 3
239000000205 acacia gum Substances 0.000 description 3
235000010489 acacia gum Nutrition 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
150000008044 alkali metal hydroxides Chemical class 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
229910052987 metal hydride Inorganic materials 0.000 description 3
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
235000020824 obesity Nutrition 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
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 3
239000011736 potassium bicarbonate Substances 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
229910000105 potassium hydride Inorganic materials 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
235000017550 sodium carbonate Nutrition 0.000 description 3
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
238000010998 test method Methods 0.000 description 3
YEKUWOWHPVKTCQ-UHFFFAOYSA-M tetraethylazanium;fluoride;hydrate Chemical compound O.[F-].CC[N+](CC)(CC)CC YEKUWOWHPVKTCQ-UHFFFAOYSA-M 0.000 description 3
239000008096 xylene Substances 0.000 description 3
CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical class C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 2
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
125000006039 1-hexenyl group Chemical group 0.000 description 2
125000006023 1-pentenyl group Chemical group 0.000 description 2
125000006017 1-propenyl group Chemical group 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
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235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000007547 defect Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
NCBFTYFOPLPRBX-UHFFFAOYSA-N dimethyl azodicarboxylate Substances COC(=O)N=NC(=O)OC NCBFTYFOPLPRBX-UHFFFAOYSA-N 0.000 description 1
230000000667 effect on insulin Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
FQZSYCUEVDUKOV-UHFFFAOYSA-N ethyl 2-[(n-(2-ethoxy-2-oxoethyl)anilino)methyl]-4-methoxybenzoate Chemical compound C=1C=CC=CC=1N(CC(=O)OCC)CC1=CC(OC)=CC=C1C(=O)OCC FQZSYCUEVDUKOV-UHFFFAOYSA-N 0.000 description 1
MLSGRWDEDYJNER-UHFFFAOYSA-N ethyl 2-anilinoacetate Chemical compound CCOC(=O)CNC1=CC=CC=C1 MLSGRWDEDYJNER-UHFFFAOYSA-N 0.000 description 1
FIOUABZFZNZORE-UHFFFAOYSA-N ethyl 4-hydroxy-7-methoxy-2-phenyl-3,4-dihydro-1h-isoquinoline-3-carboxylate Chemical compound CCOC(=O)C1C(O)C2=CC=C(OC)C=C2CN1C1=CC=CC=C1 FIOUABZFZNZORE-UHFFFAOYSA-N 0.000 description 1
OCVWTVSURRGDPJ-UHFFFAOYSA-N ethyl 4-methoxy-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(OC)C=C1C OCVWTVSURRGDPJ-UHFFFAOYSA-N 0.000 description 1
HCTAITIVOMIGHS-UHFFFAOYSA-N ethyl 7-methoxy-2-phenyl-3,4-dihydro-1h-isoquinoline-3-carboxylate Chemical compound CCOC(=O)C1CC2=CC=C(OC)C=C2CN1C1=CC=CC=C1 HCTAITIVOMIGHS-UHFFFAOYSA-N 0.000 description 1
ZCGOMXZZBDJXBF-UHFFFAOYSA-N ethyl 7-methoxy-4-oxo-2-phenyl-1,3-dihydroisoquinoline-3-carboxylate Chemical compound C1C2=CC(OC)=CC=C2C(=O)C(C(=O)OCC)N1C1=CC=CC=C1 ZCGOMXZZBDJXBF-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008187 granular material Substances 0.000 description 1
GRTWTVFDPBKQNU-UHFFFAOYSA-N hexa-2,4-dienoyl chloride Chemical compound CC=CC=CC(Cl)=O GRTWTVFDPBKQNU-UHFFFAOYSA-N 0.000 description 1
UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000003451 hyperinsulinaemic effect Effects 0.000 description 1
201000008980 hyperinsulinism Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
208000006443 lactic acidosis Diseases 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
NCBFTYFOPLPRBX-AATRIKPKSA-N methyl (ne)-n-methoxycarbonyliminocarbamate Chemical compound COC(=O)\N=N\C(=O)OC NCBFTYFOPLPRBX-AATRIKPKSA-N 0.000 description 1
LHPKCPJBQHPGAV-UHFFFAOYSA-N methyl 2-[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]acetate Chemical compound O1C(C)=C(CC(=O)OC)N=C1C1=CC=C(C(C)C)C=C1 LHPKCPJBQHPGAV-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
CPHCIYGRSFZNRD-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1h-indazol-3-yl)methanamine Chemical compound C1CCCC2=C1NN=C2CNC CPHCIYGRSFZNRD-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
229960005095 pioglitazone Drugs 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 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
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
229960004586 rosiglitazone Drugs 0.000 description 1
XOVSRHHCHKUFKM-UHFFFAOYSA-N s-methylthiohydroxylamine Chemical compound CSN XOVSRHHCHKUFKM-UHFFFAOYSA-N 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
DDFYFBUWEBINLX-UHFFFAOYSA-M tetramethylammonium bromide Chemical compound [Br-].C[N+](C)(C)C DDFYFBUWEBINLX-UHFFFAOYSA-M 0.000 description 1
150000003548 thiazolidines Chemical class 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
FPZZZGJWXOHLDJ-UHFFFAOYSA-N trihexylphosphane Chemical compound CCCCCCP(CCCCCC)CCCCCC FPZZZGJWXOHLDJ-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
RMZAYIKUYWXQPB-UHFFFAOYSA-N trioctylphosphane Chemical compound CCCCCCCCP(CCCCCCCC)CCCCCCCC RMZAYIKUYWXQPB-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Child & Adolescent Psychology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

NO20035332A 2001-05-29 2003-11-28 Heterocykliske derivater og farmasoytiske midler inneholdende disse NO326559B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP2001161488		2001-05-29
PCT/JP2002/005098 WO2002096904A1 (en)	2001-05-29	2002-05-27	Novel heterocyclic derivatives and medicinal use thereof

Publications (2)

Publication Number	Publication Date
NO20035332D0 NO20035332D0 (no)	2003-11-28
NO326559B1 true NO326559B1 (no)	2009-01-12

Family

ID=19004755

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20035332A NO326559B1 (no)	2001-05-29	2003-11-28	Heterocykliske derivater og farmasoytiske midler inneholdende disse

Country Status (22)

Country	Link
US (1)	US6872732B2 (es)
EP (1)	EP1398313A4 (es)
JP (1)	JP4279137B2 (es)
KR (1)	KR100874677B1 (es)
CN (1)	CN1522253A (es)
AR (1)	AR036037A1 (es)
AU (1)	AU2002308891B2 (es)
BR (1)	BR0209735A (es)
CA (1)	CA2448639A1 (es)
CO (1)	CO5540322A2 (es)
CZ (1)	CZ20033415A3 (es)
HU (1)	HUP0400023A2 (es)
IL (1)	IL159084A0 (es)
MX (1)	MXPA03010867A (es)
NO (1)	NO326559B1 (es)
NZ (1)	NZ530313A (es)
PL (1)	PL367676A1 (es)
RU (1)	RU2287529C2 (es)
TW (1)	TWI243172B (es)
WO (1)	WO2002096904A1 (es)
YU (1)	YU94203A (es)
ZA (1)	ZA200309513B (es)

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PL367639A1 (en)	2001-05-29	2005-03-07	Kyoto Pharmaceutical Industries, Ltd.	Novel heterocyclic compound and medicinal use thereof
US6867224B2 (en)	2002-03-07	2005-03-15	Warner-Lambert Company	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
JP2006514069A (ja)	2003-01-06	2006-04-27	イーライリリーアンドカンパニー	Ｐｐａｒ調節因子としての融合複素環式誘導体
US7244763B2 (en)	2003-04-17	2007-07-17	Warner Lambert Company Llc	Compounds that modulate PPAR activity and methods of preparation
US6987118B2 (en)	2003-05-21	2006-01-17	Pfizer Inc.	Tetrahydroisoquinoline derivatives as PPAR-alpha activators
JP4805552B2 (ja) *	2003-05-30	2011-11-02	武田薬品工業株式会社	縮合環化合物
WO2004106276A1 (ja) *	2003-05-30	2004-12-09	Takeda Pharmaceutical Company Limited	縮合環化合物
TWI359810B (en) *	2004-11-04	2012-03-11	Mitsubishi Tanabe Pharma Corp	Carboxylic acid derivative containing thiazole rin
JP5225076B2 (ja) *	2006-04-27	2013-07-03	田辺三菱製薬株式会社	チアゾール環を含むカルボン酸誘導体の医薬用途
WO2012033195A1 (ja) *	2010-09-10	2012-03-15	京都薬品工業株式会社	複素環化合物
HRP20190039T1 (hr)	2014-04-04	2019-03-08	Syros Pharmaceuticals, Inc.	Inhibitori ciklin-ovisne kinaze 7 (cdk7)
WO2020013116A1 (ja) *	2018-07-10	2020-01-16	京都薬品工業株式会社	Ｐｔｐ－１ｂ阻害剤およびその用途

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JPS6051189A (ja) *	1983-08-30	1985-03-22	Sankyo Co Ltd	チアゾリジン誘導体およびその製造法
AR240698A1 (es) *	1985-01-19	1990-09-28	Takeda Chemical Industries Ltd	Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales
EP0306228B1 (en) *	1987-09-04	1999-11-17	Beecham Group Plc	Substituted thiazolidinedione derivatives
US5246943A (en) *	1992-05-19	1993-09-21	Warner-Lambert Company	Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties
GB9604242D0 (en)	1996-02-28	1996-05-01	Glaxo Wellcome Inc	Chemical compounds
CA2259431A1 (en) *	1996-07-01	1998-01-08	Eli Lilly And Company	Hypoglycemic and hypolipidemic compounds
JP2000515133A (ja)	1996-07-01	2000-11-14	イーライ・リリー・アンド・カンパニー	血糖降下性および脂質低下性の化合物
GB9817118D0 (en) *	1998-08-07	1998-10-07	Glaxo Group Ltd	Pharmaceutical compounds
CZ20021911A3 (cs)	1999-12-03	2002-10-16	Kyoto Pharmaceutical Industries, Ltd.	Nové heterocyklické sloučeniny a jejich soli a jejich vyuľití v lékařství
US20020037897A1 (en)	2000-08-07	2002-03-28	3-Dimensional Pharmaceuticals, Inc.	Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists
PL367639A1 (en)	2001-05-29	2005-03-07	Kyoto Pharmaceutical Industries, Ltd.	Novel heterocyclic compound and medicinal use thereof

2002
- 2002-05-27 MX MXPA03010867A patent/MXPA03010867A/es active IP Right Grant
- 2002-05-27 KR KR1020037015518A patent/KR100874677B1/ko not_active Expired - Fee Related
- 2002-05-27 CA CA002448639A patent/CA2448639A1/en not_active Abandoned
- 2002-05-27 NZ NZ530313A patent/NZ530313A/en unknown
- 2002-05-27 PL PL02367676A patent/PL367676A1/xx not_active IP Right Cessation
- 2002-05-27 EP EP02774071A patent/EP1398313A4/en not_active Withdrawn
- 2002-05-27 YU YU94203A patent/YU94203A/sh unknown
- 2002-05-27 JP JP2003500083A patent/JP4279137B2/ja not_active Expired - Fee Related
- 2002-05-27 BR BR0209735-4A patent/BR0209735A/pt not_active IP Right Cessation
- 2002-05-27 CN CNA028109627A patent/CN1522253A/zh active Pending
- 2002-05-27 AU AU2002308891A patent/AU2002308891B2/en not_active Ceased
- 2002-05-27 CZ CZ20033415A patent/CZ20033415A3/cs unknown
- 2002-05-27 RU RU2003137576/04A patent/RU2287529C2/ru not_active IP Right Cessation
- 2002-05-27 US US10/478,863 patent/US6872732B2/en not_active Expired - Fee Related
- 2002-05-27 WO PCT/JP2002/005098 patent/WO2002096904A1/ja not_active Ceased
- 2002-05-27 IL IL15908402A patent/IL159084A0/xx unknown
- 2002-05-27 HU HU0400023A patent/HUP0400023A2/hu unknown
- 2002-05-28 TW TW091111323A patent/TWI243172B/zh not_active IP Right Cessation
- 2002-05-29 AR ARP020102003A patent/AR036037A1/es unknown
2003
- 2003-11-28 NO NO20035332A patent/NO326559B1/no unknown
- 2003-12-08 ZA ZA200309513A patent/ZA200309513B/xx unknown
- 2003-12-29 CO CO03112805A patent/CO5540322A2/es not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO20035332D0 (no)	2003-11-28
ZA200309513B (en)	2004-12-08
CO5540322A2 (es)	2005-07-29
EP1398313A4 (en)	2005-11-16
KR100874677B1 (ko)	2008-12-18
RU2287529C2 (ru)	2006-11-20
IL159084A0 (en)	2004-05-12
AR036037A1 (es)	2004-08-04
BR0209735A (pt)	2004-07-27
AU2002308891B2 (en)	2007-09-06
NZ530313A (en)	2005-06-24
TWI243172B (en)	2005-11-11
CZ20033415A3 (cs)	2004-06-16
HUP0400023A2 (hu)	2004-04-28
YU94203A (sh)	2006-08-17
RU2003137576A (ru)	2005-05-20
EP1398313A1 (en)	2004-03-17
JPWO2002096904A1 (ja)	2004-09-09
MXPA03010867A (es)	2004-02-27
KR20040004663A (ko)	2004-01-13
JP4279137B2 (ja)	2009-06-17
PL367676A1 (en)	2005-03-07
CN1522253A (zh)	2004-08-18
US20040180924A1 (en)	2004-09-16
WO2002096904A1 (en)	2002-12-05
CA2448639A1 (en)	2002-12-05
US6872732B2 (en)	2005-03-29

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