JP2003515583A - 新規三置換フェニル誘導体および類似体 - Google Patents
新規三置換フェニル誘導体および類似体Info
- Publication number
- JP2003515583A JP2003515583A JP2001541859A JP2001541859A JP2003515583A JP 2003515583 A JP2003515583 A JP 2003515583A JP 2001541859 A JP2001541859 A JP 2001541859A JP 2001541859 A JP2001541859 A JP 2001541859A JP 2003515583 A JP2003515583 A JP 2003515583A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- defined above
- aryl
- alkylaryl
- 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 150000002431 hydrogen Chemical group 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 230000002829 reductive effect Effects 0.000 claims description 22
- 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
- 150000003839 salts Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 12
- 239000000651 prodrug Chemical group 0.000 claims description 11
- 229940002612 prodrug Drugs 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 102000004877 Insulin Human genes 0.000 claims description 7
- 108090001061 Insulin Proteins 0.000 claims description 7
- 229940125396 insulin Drugs 0.000 claims description 7
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- 239000012453 solvate Chemical group 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 24
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 17
- 206010022489 Insulin Resistance Diseases 0.000 abstract description 13
- 230000008569 process Effects 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 67
- 239000000126 substance Substances 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 59
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- -1 metformin Chemical class 0.000 description 47
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 239000000047 product Substances 0.000 description 37
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 239000000203 mixture Substances 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- 125000006239 protecting group Chemical group 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 238000010561 standard procedure Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000002953 preparative HPLC Methods 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 9
- 239000005695 Ammonium acetate Substances 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229940043376 ammonium acetate Drugs 0.000 description 9
- 235000019257 ammonium acetate Nutrition 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- CBLURUVVHKBIPR-UHFFFAOYSA-N 2-(4-methylsulfonyloxyphenyl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=CC=C(OS(C)(=O)=O)C=C1 CBLURUVVHKBIPR-UHFFFAOYSA-N 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 208000032928 Dyslipidaemia Diseases 0.000 description 6
- 208000017170 Lipid metabolism disease Diseases 0.000 description 6
- 238000006751 Mitsunobu reaction Methods 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 239000003875 Wang resin Substances 0.000 description 3
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- CKSRFHWWBKRUKA-UHFFFAOYSA-N ethyl 2-ethoxyacetate Chemical compound CCOCC(=O)OCC CKSRFHWWBKRUKA-UHFFFAOYSA-N 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 3
- 201000008980 hyperinsulinism Diseases 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 3
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical compound OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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- 241001000171 Chira Species 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
-
- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9904421-6 | 1999-12-03 | ||
| SE9904421A SE9904421D0 (sv) | 1999-12-03 | 1999-12-03 | New compounds |
| PCT/SE2000/002385 WO2001040172A1 (en) | 1999-12-03 | 2000-11-29 | New tri-substituted phenyl derivatives and analogues |
Publications (2)
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| JP2003515583A true JP2003515583A (ja) | 2003-05-07 |
| JP2003515583A5 JP2003515583A5 (enExample) | 2007-09-06 |
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| JP2001541859A Pending JP2003515583A (ja) | 1999-12-03 | 2000-11-29 | 新規三置換フェニル誘導体および類似体 |
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| US (1) | US6750252B2 (enExample) |
| EP (1) | EP1237856B1 (enExample) |
| JP (1) | JP2003515583A (enExample) |
| KR (1) | KR100787072B1 (enExample) |
| CN (1) | CN1206212C (enExample) |
| AR (1) | AR033957A1 (enExample) |
| AT (1) | ATE266633T1 (enExample) |
| AU (1) | AU766533B2 (enExample) |
| BR (1) | BR0016130A (enExample) |
| CA (1) | CA2392039A1 (enExample) |
| DE (1) | DE60010747T2 (enExample) |
| DK (1) | DK1237856T3 (enExample) |
| ES (1) | ES2219425T3 (enExample) |
| IL (2) | IL149517A0 (enExample) |
| MX (1) | MXPA02005223A (enExample) |
| MY (1) | MY124727A (enExample) |
| NO (1) | NO20022590L (enExample) |
| PT (1) | PT1237856E (enExample) |
| SE (1) | SE9904421D0 (enExample) |
| TR (1) | TR200401716T4 (enExample) |
| TW (1) | TWI224590B (enExample) |
| WO (1) | WO2001040172A1 (enExample) |
| ZA (1) | ZA200203798B (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008504312A (ja) * | 2004-06-28 | 2008-02-14 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | フェニルカルボン酸誘導体および糖尿病の処置のためのその使用 |
| JP2010529099A (ja) * | 2007-06-05 | 2010-08-26 | ガルデルマ・リサーチ・アンド・デヴェロップメント | Ｐｐａｒタイプ受容体の活性化剤である３‐フェニルアクリル酸の新規誘導体、その調製方法および化粧品組成物または医薬組成物におけるその使用 |
| JP2010529098A (ja) * | 2007-06-05 | 2010-08-26 | ガルデルマ・リサーチ・アンド・デヴェロップメント | Ｐｐａｒ型受容体の活性化剤である新規な３‐フェニルプロパン酸誘導体、その製造方法、および化粧品組成物または医薬組成物におけるその使用 |
| JP2010535838A (ja) * | 2007-08-13 | 2010-11-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規調製方法 |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6369067B1 (en) | 1997-10-27 | 2002-04-09 | Dr. Reddy's Research Foundation | Monocyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them |
| AU1198699A (en) | 1997-10-27 | 1999-04-23 | Dr. Reddy's Research Foundation | Novel heterocyclic compounds and their use in medicine, process for their reparation and pharmaceutical compositions containing them |
| AU749505B2 (en) | 1997-10-27 | 2002-06-27 | Dr. Reddy's Laboratories Limited | Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them |
| US6440961B1 (en) | 1997-10-27 | 2002-08-27 | Dr. Reddy's Research Foundation | Tricyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them |
| CA2307068C (en) | 1997-10-27 | 2007-04-10 | Dr. Reddy's Research Foundation | Bicyclic compounds, process for their preparation and pharmaceutical compositions containing them |
| US6531596B1 (en) | 1998-10-29 | 2003-03-11 | Dr. Reddy's Laboratories Ltd. | Process for the preparation of new antidiabetic agents |
| JP2002528535A (ja) | 1998-10-29 | 2002-09-03 | ドクター・レディーズ・リサーチ・ファウンデーション | 新規抗糖尿病剤製造の改良方法 |
| US6897199B2 (en) | 2001-02-05 | 2005-05-24 | Dr. Reddy's Laboratories Ltd. | Pharmaceutically acceptable salts of phenoxazine and phenothiazine compounds |
| SE0101386D0 (sv) | 2001-04-20 | 2001-04-20 | Astrazeneca Ab | New compounds |
| CN1589258A (zh) * | 2001-10-16 | 2005-03-02 | 雷迪实验室有限公司 | 新的β－苯基－α－氧取代的丙酸衍生物,它的制备方法和它们制备药学上重要的化合物的应用 |
| UA82835C2 (en) * | 2001-12-03 | 2008-05-26 | Reddys Lab Ltd Dr | ?-aryl-?-oxysubstituted propionuc acid derivatives and pharmaceutical composition based thereon |
| SE0104333D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| TW200817369A (en) * | 2006-05-22 | 2008-04-16 | Elan Pharm Inc | Preparation of polymer conjugates of therapeutic, agricultural and food additive compounds |
| JP5404429B2 (ja) | 2007-03-08 | 2014-01-29 | アルビレオ・アクチボラグ | ２−置換３−フェニルプロピオン酸誘導体および炎症性腸疾患の治療におけるそれらの使用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9801992D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
| SE9801990D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl propionic acid derivatives and analogs |
| MA26634A1 (fr) | 1998-06-04 | 2004-12-20 | Astra Ab | Nouveaux derives de l'acide 3-aryl propionique et analogues |
-
1999
- 1999-12-03 SE SE9904421A patent/SE9904421D0/xx unknown
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2000
- 2000-11-21 TW TW089124657A patent/TWI224590B/zh not_active IP Right Cessation
- 2000-11-29 WO PCT/SE2000/002385 patent/WO2001040172A1/en not_active Ceased
- 2000-11-29 US US10/148,850 patent/US6750252B2/en not_active Expired - Fee Related
- 2000-11-29 PT PT00983619T patent/PT1237856E/pt unknown
- 2000-11-29 EP EP00983619A patent/EP1237856B1/en not_active Expired - Lifetime
- 2000-11-29 CN CNB008163812A patent/CN1206212C/zh not_active Expired - Fee Related
- 2000-11-29 IL IL14951700A patent/IL149517A0/xx active IP Right Grant
- 2000-11-29 JP JP2001541859A patent/JP2003515583A/ja active Pending
- 2000-11-29 ES ES00983619T patent/ES2219425T3/es not_active Expired - Lifetime
- 2000-11-29 DE DE60010747T patent/DE60010747T2/de not_active Expired - Fee Related
- 2000-11-29 KR KR1020027007057A patent/KR100787072B1/ko not_active Expired - Fee Related
- 2000-11-29 TR TR2004/01716T patent/TR200401716T4/xx unknown
- 2000-11-29 MX MXPA02005223A patent/MXPA02005223A/es active IP Right Grant
- 2000-11-29 BR BR0016130-6A patent/BR0016130A/pt not_active Application Discontinuation
- 2000-11-29 DK DK00983619T patent/DK1237856T3/da active
- 2000-11-29 AT AT00983619T patent/ATE266633T1/de not_active IP Right Cessation
- 2000-11-29 AU AU20351/01A patent/AU766533B2/en not_active Ceased
- 2000-11-29 CA CA002392039A patent/CA2392039A1/en not_active Abandoned
- 2000-11-30 MY MYPI20005602A patent/MY124727A/en unknown
- 2000-12-01 AR ARP000106386A patent/AR033957A1/es not_active Application Discontinuation
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2002
- 2002-05-07 IL IL149517A patent/IL149517A/en not_active IP Right Cessation
- 2002-05-13 ZA ZA200203798A patent/ZA200203798B/en unknown
- 2002-05-31 NO NO20022590A patent/NO20022590L/no not_active Application Discontinuation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008504312A (ja) * | 2004-06-28 | 2008-02-14 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | フェニルカルボン酸誘導体および糖尿病の処置のためのその使用 |
| JP2010529099A (ja) * | 2007-06-05 | 2010-08-26 | ガルデルマ・リサーチ・アンド・デヴェロップメント | Ｐｐａｒタイプ受容体の活性化剤である３‐フェニルアクリル酸の新規誘導体、その調製方法および化粧品組成物または医薬組成物におけるその使用 |
| JP2010529098A (ja) * | 2007-06-05 | 2010-08-26 | ガルデルマ・リサーチ・アンド・デヴェロップメント | Ｐｐａｒ型受容体の活性化剤である新規な３‐フェニルプロパン酸誘導体、その製造方法、および化粧品組成物または医薬組成物におけるその使用 |
| JP2010535838A (ja) * | 2007-08-13 | 2010-11-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規調製方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL149517A (en) | 2007-07-04 |
| WO2001040172A1 (en) | 2001-06-07 |
| DK1237856T3 (da) | 2004-08-02 |
| AU766533B2 (en) | 2003-10-16 |
| DE60010747D1 (de) | 2004-06-17 |
| KR100787072B1 (ko) | 2007-12-21 |
| MY124727A (en) | 2006-06-30 |
| AU2035101A (en) | 2001-06-12 |
| TWI224590B (en) | 2004-12-01 |
| US6750252B2 (en) | 2004-06-15 |
| CA2392039A1 (en) | 2001-06-07 |
| EP1237856B1 (en) | 2004-05-12 |
| DE60010747T2 (de) | 2005-05-19 |
| SE9904421D0 (sv) | 1999-12-03 |
| ATE266633T1 (de) | 2004-05-15 |
| CN1402703A (zh) | 2003-03-12 |
| IL149517A0 (en) | 2002-11-10 |
| NO20022590L (no) | 2002-07-29 |
| NO20022590D0 (no) | 2002-05-31 |
| EP1237856A1 (en) | 2002-09-11 |
| ZA200203798B (en) | 2003-10-29 |
| BR0016130A (pt) | 2002-08-20 |
| US20030149104A1 (en) | 2003-08-07 |
| ES2219425T3 (es) | 2004-12-01 |
| CN1206212C (zh) | 2005-06-15 |
| PT1237856E (pt) | 2004-08-31 |
| TR200401716T4 (tr) | 2004-09-21 |
| MXPA02005223A (es) | 2003-09-25 |
| AR033957A1 (es) | 2004-01-21 |
| KR20020067537A (ko) | 2002-08-22 |
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