TWI551590B - 經取代之苯吖唑衍生物 - Google Patents
經取代之苯吖唑衍生物 Download PDFInfo
- Publication number
- TWI551590B TWI551590B TW102101765A TW102101765A TWI551590B TW I551590 B TWI551590 B TW I551590B TW 102101765 A TW102101765 A TW 102101765A TW 102101765 A TW102101765 A TW 102101765A TW I551590 B TWI551590 B TW I551590B
- Authority
- TW
- Taiwan
- Prior art keywords
- mmol
- compound
- added
- solution
- room temperature
- Prior art date
Links
- IRTLROCMFSDSNF-UHFFFAOYSA-N 2-phenyl-1h-pyrrole Chemical class C1=CNC(C=2C=CC=CC=2)=C1 IRTLROCMFSDSNF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 247
- 150000003839 salts Chemical class 0.000 claims description 47
- -1 hydroxyisopropyl Chemical group 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 18
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
- 210000000496 pancreas Anatomy 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- XEAGYBCOIAPRMG-CYBMUJFWSA-N 1-[4-[4-[(1r)-1-[6-(cyclopropanecarbonyl)pyridin-3-yl]oxyethyl]triazol-2-yl]-2-fluorophenyl]-3-(2-hydroxyethyl)urea Chemical compound O([C@H](C)C1=NN(N=C1)C=1C=C(F)C(NC(=O)NCCO)=CC=1)C(C=N1)=CC=C1C(=O)C1CC1 XEAGYBCOIAPRMG-CYBMUJFWSA-N 0.000 claims description 3
- NMGGJYWTBWYIMB-GICMACPYSA-N 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]ethyl]-1,3-thiazol-2-yl]-2-fluoro-n-[(2r)-1-hydroxypropan-2-yl]benzamide Chemical compound C1=C(F)C(C(=O)N[C@@H](CO)C)=CC=C1C1=NC=C(C(C)OC=2C=CC(=CC=2)C(=O)C2CC2)S1 NMGGJYWTBWYIMB-GICMACPYSA-N 0.000 claims description 3
- IUUUELDAAJIQMX-CKAQCJTGSA-N 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]propyl]tetrazol-2-yl]-2-fluoro-n-[(2r)-1-hydroxypropan-2-yl]benzamide Chemical compound N1=NN(C=2C=C(F)C(C(=O)N[C@H](C)CO)=CC=2)N=C1C(CC)OC(C=C1)=CC=C1C(=O)C1CC1 IUUUELDAAJIQMX-CKAQCJTGSA-N 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- CEZQXLQNJWSMTA-UHFFFAOYSA-N 1-[4-[4-[1-[4-(cyclopropanecarbonyl)phenoxy]propyl]triazol-2-yl]-2-fluorophenyl]-3-(2-hydroxyethyl)urea Chemical compound C1=NN(C=2C=C(F)C(NC(=O)NCCO)=CC=2)N=C1C(CC)OC(C=C1)=CC=C1C(=O)C1CC1 CEZQXLQNJWSMTA-UHFFFAOYSA-N 0.000 claims description 2
- SKOMQZMYGIJASR-SOHPYSCWSA-N 4-[4-[(1r)-1-[6-(cyclopropanecarbonyl)pyridin-3-yl]oxyethyl]triazol-2-yl]-n-[(2r,3r)-3,4-dihydroxybutan-2-yl]-2-fluorobenzamide Chemical compound C1=C(F)C(C(=O)N[C@H](C)[C@@H](O)CO)=CC=C1N1N=C([C@@H](C)OC=2C=NC(=CC=2)C(=O)C2CC2)C=N1 SKOMQZMYGIJASR-SOHPYSCWSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 351
- 239000000243 solution Substances 0.000 description 178
- 235000019439 ethyl acetate Nutrition 0.000 description 143
- 239000002904 solvent Substances 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- 238000005160 1H NMR spectroscopy Methods 0.000 description 115
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 113
- 239000000203 mixture Substances 0.000 description 110
- 239000011541 reaction mixture Substances 0.000 description 104
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 101
- 238000003756 stirring Methods 0.000 description 89
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 86
- 239000012044 organic layer Substances 0.000 description 85
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- 239000013078 crystal Substances 0.000 description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
- 229920006395 saturated elastomer Polymers 0.000 description 61
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 238000001914 filtration Methods 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 235000017557 sodium bicarbonate Nutrition 0.000 description 30
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 239000007864 aqueous solution Substances 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000011780 sodium chloride Substances 0.000 description 24
- 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 24
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000008280 blood Substances 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 17
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 238000001816 cooling Methods 0.000 description 16
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 239000012295 chemical reaction liquid Substances 0.000 description 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 239000008103 glucose Substances 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 11
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- GVBHKNVCIKUPCZ-UHFFFAOYSA-N cyclopropyl-(4-hydroxyphenyl)methanone Chemical compound C1=CC(O)=CC=C1C(=O)C1CC1 GVBHKNVCIKUPCZ-UHFFFAOYSA-N 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
- 230000002218 hypoglycaemic effect Effects 0.000 description 5
- 239000011777 magnesium Chemical class 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 239000004367 Lipase Substances 0.000 description 4
- 102000004882 Lipase Human genes 0.000 description 4
- 108090001060 Lipase Proteins 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 235000019421 lipase Nutrition 0.000 description 4
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 239000004925 Acrylic resin Substances 0.000 description 3
- 229920000178 Acrylic resin Polymers 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 3
- 241001661345 Moesziomyces antarcticus Species 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 150000002148 esters Chemical class 0.000 description 3
- 235000003642 hunger Nutrition 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 239000003538 oral antidiabetic agent Substances 0.000 description 3
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Chemical class 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000011592 zinc chloride Substances 0.000 description 3
- 235000005074 zinc chloride Nutrition 0.000 description 3
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- JVWXSUFBGRQWMA-UHFFFAOYSA-N 2-[4-(cyclopropanecarbonyl)phenoxy]propanoic acid Chemical compound CC(Oc1ccc(cc1)C(=O)C1CC1)C(O)=O JVWXSUFBGRQWMA-UHFFFAOYSA-N 0.000 description 2
- SURMYNZXHKLDFO-UHFFFAOYSA-N 2-bromopropanedial Chemical compound O=CC(Br)C=O SURMYNZXHKLDFO-UHFFFAOYSA-N 0.000 description 2
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 2
- RQCBPOPQTLHDFC-UHFFFAOYSA-N 2-phenyl-1,3-oxazole Chemical class C1=COC(C=2C=CC=CC=2)=N1 RQCBPOPQTLHDFC-UHFFFAOYSA-N 0.000 description 2
- YUEKWNYGXNDQRO-UHFFFAOYSA-N 5-hydroxypyridine-2-carbonitrile Chemical compound OC1=CC=C(C#N)N=C1 YUEKWNYGXNDQRO-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical class OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229940039227 diagnostic agent Drugs 0.000 description 2
- 239000000032 diagnostic agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- XIMFCGSNSKXPBO-UHFFFAOYSA-N ethyl 2-bromobutanoate Chemical compound CCOC(=O)C(Br)CC XIMFCGSNSKXPBO-UHFFFAOYSA-N 0.000 description 2
- 208000004104 gestational diabetes Diseases 0.000 description 2
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- ACEONLNNWKIPTM-UHFFFAOYSA-N methyl 2-bromopropanoate Chemical compound COC(=O)C(C)Br ACEONLNNWKIPTM-UHFFFAOYSA-N 0.000 description 2
- BPAKMNNACPYTAY-UHFFFAOYSA-N methyl 4-amino-2-fluorobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1F BPAKMNNACPYTAY-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 1
- YRJWBJJEWDIHJG-VIFPVBQESA-N (2S)-2-(4-methoxyphenoxy)butanenitrile Chemical compound COC1=CC=C(O[C@H](C#N)CC)C=C1 YRJWBJJEWDIHJG-VIFPVBQESA-N 0.000 description 1
- JEPGPKGGSYXGKV-YFKPBYRVSA-N (2S)-2-ethoxybutanoic acid Chemical compound CCO[C@@H](CC)C(O)=O JEPGPKGGSYXGKV-YFKPBYRVSA-N 0.000 description 1
- RVBUZBPJAGZHSQ-VKHMYHEASA-N (2s)-2-chlorobutanoic acid Chemical compound CC[C@H](Cl)C(O)=O RVBUZBPJAGZHSQ-VKHMYHEASA-N 0.000 description 1
- OTJFQRMIRKXXRS-UHFFFAOYSA-N (hydroxymethylamino)methanol Chemical class OCNCO OTJFQRMIRKXXRS-UHFFFAOYSA-N 0.000 description 1
- LWBOCLYIKNCYLH-UHFFFAOYSA-N 1-(5-hydroxypyridin-2-yl)-2-methylpropan-1-one Chemical compound OC=1C=CC(=NC1)C(C(C)C)=O LWBOCLYIKNCYLH-UHFFFAOYSA-N 0.000 description 1
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- AJWSKABLBWPCTO-UHFFFAOYSA-N 1-[2-(3-fluoro-4-methylsulfanylphenyl)-1,3-thiazol-5-yl]propan-1-ol Chemical compound FC=1C=C(C=CC1SC)C=1SC(=CN1)C(CC)O AJWSKABLBWPCTO-UHFFFAOYSA-N 0.000 description 1
- GTRSCLLPAWBLIR-UHFFFAOYSA-N 1-[5-(methoxymethoxy)pyridin-2-yl]-3-methylbutan-1-one Chemical compound COCOC=1C=CC(=NC1)C(CC(C)C)=O GTRSCLLPAWBLIR-UHFFFAOYSA-N 0.000 description 1
- SUMVTRRXURXRGY-UHFFFAOYSA-N 2-(1,1-difluoro-3-methylbutyl)-5-(methoxymethoxy)pyridine Chemical compound FC(CC(C)C)(F)C1=NC=C(C=C1)OCOC SUMVTRRXURXRGY-UHFFFAOYSA-N 0.000 description 1
- AYSLTJVSNBQFIE-UHFFFAOYSA-N 2-(3-fluoro-4-methoxycarbonylphenyl)tetrazole-5-carboxylic acid Chemical compound COC(=O)c1ccc(cc1F)-n1nnc(n1)C(O)=O AYSLTJVSNBQFIE-UHFFFAOYSA-N 0.000 description 1
- MBVGCWUBDJGTNW-UHFFFAOYSA-N 2-(3-fluoro-4-methoxycarbonylphenyl)triazole-4-carboxylic acid Chemical compound COC(=O)c1ccc(cc1F)-n1ncc(n1)C(O)=O MBVGCWUBDJGTNW-UHFFFAOYSA-N 0.000 description 1
- DQJXFCBRZNXPOP-UHFFFAOYSA-N 2-(3-fluoro-4-methylsulfanylphenyl)-1,3-thiazole-5-carbaldehyde Chemical compound FC=1C=C(C=CC1SC)C=1SC(=CN1)C=O DQJXFCBRZNXPOP-UHFFFAOYSA-N 0.000 description 1
- QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
- SYGLDTUHTDHVAM-UHFFFAOYSA-N 2-[4-(cyclopropanecarbonyl)phenoxy]butanenitrile Chemical compound C1(CC1)C(=O)C1=CC=C(OC(C#N)CC)C=C1 SYGLDTUHTDHVAM-UHFFFAOYSA-N 0.000 description 1
- UAELODXHSXRJCQ-UHFFFAOYSA-N 2-[4-(cyclopropanecarbonyl)phenoxy]propanenitrile Chemical compound C1(CC1)C(=O)C1=CC=C(OC(C#N)C)C=C1 UAELODXHSXRJCQ-UHFFFAOYSA-N 0.000 description 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- OENRTSFIBLMLSD-UHFFFAOYSA-N 3-fluoro-4-[(2-methylpropan-2-yl)oxycarbonyl]benzoic acid Chemical compound CC(C)(C)OC(=O)c1ccc(cc1F)C(O)=O OENRTSFIBLMLSD-UHFFFAOYSA-N 0.000 description 1
- BHCZVQVKEQQOAN-UHFFFAOYSA-N 3-fluoro-4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1F BHCZVQVKEQQOAN-UHFFFAOYSA-N 0.000 description 1
- MJXODBIJWTVJND-HXUWFJFHSA-N 4-[4-[(1R)-1-[4-(cyclopropanecarbonyl)phenoxy]propyl]triazol-2-yl]-2-fluorobenzoic acid Chemical compound CC[C@@H](Oc1ccc(cc1)C(=O)C1CC1)c1cnn(n1)-c1ccc(C(O)=O)c(F)c1 MJXODBIJWTVJND-HXUWFJFHSA-N 0.000 description 1
- DLIALGQMHOTLJB-LLVKDONJSA-N 4-[4-[(1R)-1-[6-(cyclopropanecarbonyl)pyridin-3-yl]oxyethyl]triazol-2-yl]-2-fluorobenzoic acid Chemical compound C[C@@H](Oc1ccc(nc1)C(=O)C1CC1)c1cnn(n1)-c1ccc(C(O)=O)c(F)c1 DLIALGQMHOTLJB-LLVKDONJSA-N 0.000 description 1
- FFIKJVLLSJVJDC-UHFFFAOYSA-N 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]ethyl]-1,3-thiazol-2-yl]-2-fluorobenzoic acid Chemical compound CC(Oc1ccc(cc1)C(=O)C1CC1)c1cnc(s1)-c1ccc(C(O)=O)c(F)c1 FFIKJVLLSJVJDC-UHFFFAOYSA-N 0.000 description 1
- PSWYLOBXTHEJMB-UHFFFAOYSA-N 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]propyl]tetrazol-2-yl]-2-fluorobenzoic acid Chemical compound CCC(Oc1ccc(cc1)C(=O)C1CC1)c1nnn(n1)-c1ccc(C(O)=O)c(F)c1 PSWYLOBXTHEJMB-UHFFFAOYSA-N 0.000 description 1
- UPFBKIRZUNGWMH-KWCCSABGSA-N 4-[5-[1-[6-(cyclopropanecarbonyl)pyridin-3-yl]oxyethyl]-1,3-thiazol-2-yl]-2-fluoro-N-[(2R)-1-hydroxypropan-2-yl]benzamide Chemical compound C1(CC1)C(=O)C1=CC=C(C=N1)OC(C)C1=CN=C(S1)C1=CC(=C(C(=O)N[C@@H](CO)C)C=C1)F UPFBKIRZUNGWMH-KWCCSABGSA-N 0.000 description 1
- RLMBRRQWBTWGMB-UHFFFAOYSA-N 4-amino-3-fluorobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1F RLMBRRQWBTWGMB-UHFFFAOYSA-N 0.000 description 1
- RMYOGXPGIDWJLU-UHFFFAOYSA-N 4-bromo-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(F)=C1 RMYOGXPGIDWJLU-UHFFFAOYSA-N 0.000 description 1
- IDYRNDBLKJUGKW-UHFFFAOYSA-N 4-methylsulfanylbenzenecarbothioamide Chemical compound CSC1=CC=C(C(N)=S)C=C1 IDYRNDBLKJUGKW-UHFFFAOYSA-N 0.000 description 1
- GAHCNYHAKKGGHF-UHFFFAOYSA-N 5,5-dimethylhexan-1-amine Chemical class CC(C)(C)CCCCN GAHCNYHAKKGGHF-UHFFFAOYSA-N 0.000 description 1
- JQWJFHVUZACICO-UHFFFAOYSA-N 5-(methoxymethoxy)pyridine-2-carbonitrile Chemical compound COCOC1=CC=C(C#N)N=C1 JQWJFHVUZACICO-UHFFFAOYSA-N 0.000 description 1
- BCOHXEMKSKFYGI-UHFFFAOYSA-N 6-(1,1-difluoro-3-methylbutyl)pyridin-3-ol Chemical compound CC(C)CC(F)(F)C1=CC=C(O)C=N1 BCOHXEMKSKFYGI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
- CRUVEKYEKBCADV-UHFFFAOYSA-N C(=O)O.C1(CC1)C(=O)C1=CC=C(C=N1)OC(C)C=1N=NN(N1)C1=CC(=CC=C1)F Chemical compound C(=O)O.C1(CC1)C(=O)C1=CC=C(C=N1)OC(C)C=1N=NN(N1)C1=CC(=CC=C1)F CRUVEKYEKBCADV-UHFFFAOYSA-N 0.000 description 1
- QFORTVWWLPKTCY-UHFFFAOYSA-N C(=O)O.C1(CC1)C(=O)C1=CC=C(OC(C)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 Chemical compound C(=O)O.C1(CC1)C(=O)C1=CC=C(OC(C)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 QFORTVWWLPKTCY-UHFFFAOYSA-N 0.000 description 1
- UTEYJKUAFGTZON-UHFFFAOYSA-N C(=O)O.C1(CC1)C(=O)C1=CC=C(OC(CC)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 Chemical compound C(=O)O.C1(CC1)C(=O)C1=CC=C(OC(CC)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 UTEYJKUAFGTZON-UHFFFAOYSA-N 0.000 description 1
- OJLUKGCLVXVXQB-UHFFFAOYSA-N C(=O)OC.C1(CC1)C(=O)C1=CC=C(C=N1)OC(C)C=1N=NN(N1)C1=CC(=CC=C1)F Chemical compound C(=O)OC.C1(CC1)C(=O)C1=CC=C(C=N1)OC(C)C=1N=NN(N1)C1=CC(=CC=C1)F OJLUKGCLVXVXQB-UHFFFAOYSA-N 0.000 description 1
- RXEHDPQEACVBGE-UHFFFAOYSA-N C(=O)OC.C1(CC1)C(=O)C1=CC=C(OC(C)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 Chemical compound C(=O)OC.C1(CC1)C(=O)C1=CC=C(OC(C)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 RXEHDPQEACVBGE-UHFFFAOYSA-N 0.000 description 1
- BWNAIXNFOAWEBQ-UHFFFAOYSA-N C(=O)OC.C1(CC1)C(=O)C1=CC=C(OC(CC)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 Chemical compound C(=O)OC.C1(CC1)C(=O)C1=CC=C(OC(CC)C2=NN(N=C2)C2=CC(=CC=C2)F)C=C1 BWNAIXNFOAWEBQ-UHFFFAOYSA-N 0.000 description 1
- HJBJYTNKEHMLJJ-UHFFFAOYSA-N C(C(C)C)C1=CC=C(C=N1)OC(C(=O)O)CC Chemical compound C(C(C)C)C1=CC=C(C=N1)OC(C(=O)O)CC HJBJYTNKEHMLJJ-UHFFFAOYSA-N 0.000 description 1
- AOXJAVYIUQHRGI-UHFFFAOYSA-N C(C)(=O)NC1=NN(N=C1)C1=CC(=C(C(=O)OC)C=C1)F Chemical compound C(C)(=O)NC1=NN(N=C1)C1=CC(=C(C(=O)OC)C=C1)F AOXJAVYIUQHRGI-UHFFFAOYSA-N 0.000 description 1
- PFBOGSVEHMDQDO-UHFFFAOYSA-N C(C)(C)(C)OC(C1=C(C(=CC=C1)C=NO)F)=O Chemical compound C(C)(C)(C)OC(C1=C(C(=CC=C1)C=NO)F)=O PFBOGSVEHMDQDO-UHFFFAOYSA-N 0.000 description 1
- FUYQSYYQMWGWAM-UHFFFAOYSA-N C(C)(C)(C)OC(C1=CC(=C(C=C1)N1N=CC(=N1)C(CC)O)F)=O Chemical compound C(C)(C)(C)OC(C1=CC(=C(C=C1)N1N=CC(=N1)C(CC)O)F)=O FUYQSYYQMWGWAM-UHFFFAOYSA-N 0.000 description 1
- DEPHCWVFSDUMJW-UHFFFAOYSA-N C(C)C1=NN(N=C1)C1=CC(=C(C(=O)O)C=C1)F Chemical compound C(C)C1=NN(N=C1)C1=CC(=C(C(=O)O)C=C1)F DEPHCWVFSDUMJW-UHFFFAOYSA-N 0.000 description 1
- OCJUIKWJIXDDQJ-MLWJPKLSSA-N C(C)OC(CO[C@H](C(=O)O)C)C Chemical compound C(C)OC(CO[C@H](C(=O)O)C)C OCJUIKWJIXDDQJ-MLWJPKLSSA-N 0.000 description 1
- GWLABMHSHNGKFW-UHFFFAOYSA-N C1(CC1)C(=O)C1=CC=C(OC(CN)CC)C=C1 Chemical compound C1(CC1)C(=O)C1=CC=C(OC(CN)CC)C=C1 GWLABMHSHNGKFW-UHFFFAOYSA-N 0.000 description 1
- IOMIZPBDHDYPRU-VIFPVBQESA-N COC1=CC=C(O[C@H](CN)CC)C=C1 Chemical compound COC1=CC=C(O[C@H](CN)CC)C=C1 IOMIZPBDHDYPRU-VIFPVBQESA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical class [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VSONIRLRQJTDSM-UHFFFAOYSA-N FC1=C(C(=O)O)C=CC(=C1)N1N=CC(=N1)C=CC Chemical compound FC1=C(C(=O)O)C=CC(=C1)N1N=CC(=N1)C=CC VSONIRLRQJTDSM-UHFFFAOYSA-N 0.000 description 1
- YXKPRBYQIXXCIP-UHFFFAOYSA-N FC1=C(C(=O)OC)C=CC(=C1)C=1SC=C(N1)C=1NC2=CC=C(C=C2C1)C Chemical compound FC1=C(C(=O)OC)C=CC(=C1)C=1SC=C(N1)C=1NC2=CC=C(C=C2C1)C YXKPRBYQIXXCIP-UHFFFAOYSA-N 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical class F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- QWCKQJZIFLGMSD-VKHMYHEASA-N L-alpha-aminobutyric acid Chemical compound CC[C@H](N)C(O)=O QWCKQJZIFLGMSD-VKHMYHEASA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000283111 Macroderes minutus Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- HTQPQRXRGKOSGL-UHFFFAOYSA-N ONNC(C1=CC=C(C=C1)O)=O Chemical compound ONNC(C1=CC=C(C=C1)O)=O HTQPQRXRGKOSGL-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- XWFYCUKXSALKQC-UHFFFAOYSA-N [4-[1-[2-(4-amino-3-fluorophenyl)triazol-4-yl]propoxy]phenyl]-cyclopropylmethanone Chemical compound NC1=C(C=C(C=C1)N1N=CC(=N1)C(CC)OC1=CC=C(C=C1)C(=O)C1CC1)F XWFYCUKXSALKQC-UHFFFAOYSA-N 0.000 description 1
- GXRJGGRQEDJBNB-LLVKDONJSA-N [5-[(1R)-1-[2-(4-amino-3-fluorophenyl)triazol-4-yl]ethoxy]pyridin-2-yl]-cyclopropylmethanone Chemical compound NC1=C(C=C(C=C1)N1N=CC(=N1)[C@@H](C)OC=1C=CC(=NC1)C(=O)C1CC1)F GXRJGGRQEDJBNB-LLVKDONJSA-N 0.000 description 1
- QEZHSXDSWBLPKD-UHFFFAOYSA-M [Br-].CC[Mg+].C1CCOC1 Chemical compound [Br-].CC[Mg+].C1CCOC1 QEZHSXDSWBLPKD-UHFFFAOYSA-M 0.000 description 1
- OZQXEOSNFMMMRD-UHFFFAOYSA-M [Cl-].CC(C)[Mg+].C1CCOC1 Chemical compound [Cl-].CC(C)[Mg+].C1CCOC1 OZQXEOSNFMMMRD-UHFFFAOYSA-M 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical class C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- FJBYSTBVNZDKFV-UHFFFAOYSA-N butyl 2-fluorobenzoate Chemical group CCCCOC(=O)C1=CC=CC=C1F FJBYSTBVNZDKFV-UHFFFAOYSA-N 0.000 description 1
- ZZHGIUCYKGFIPV-UHFFFAOYSA-N butylcarbamic acid Chemical compound CCCCNC(O)=O ZZHGIUCYKGFIPV-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- WFRFSVNLFMNFPI-UHFFFAOYSA-N cyclopropyl-(5-hydroxypyridin-2-yl)methanone Chemical compound C1(CC1)C(=O)C1=NC=C(C=C1)O WFRFSVNLFMNFPI-UHFFFAOYSA-N 0.000 description 1
- AOXQNEVSZGRZEE-UHFFFAOYSA-N cyclopropyl-[5-(methoxymethoxy)pyridin-2-yl]methanone Chemical compound N1=CC(OCOC)=CC=C1C(=O)C1CC1 AOXQNEVSZGRZEE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 150000005332 diethylamines Chemical class 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical class C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- DOHGIYNHAXCYOR-UHFFFAOYSA-N ethyl 2-(3-fluoro-4-methoxycarbonylphenyl)tetrazole-5-carboxylate Chemical compound CCOC(=O)c1nnn(n1)-c1ccc(C(=O)OC)c(F)c1 DOHGIYNHAXCYOR-UHFFFAOYSA-N 0.000 description 1
- ZLUFRENFWNLCPS-UHFFFAOYSA-N ethyl 2-(3-fluoro-4-methoxycarbonylphenyl)triazole-4-carboxylate Chemical compound CCOC(=O)c1cnn(n1)-c1ccc(C(=O)OC)c(F)c1 ZLUFRENFWNLCPS-UHFFFAOYSA-N 0.000 description 1
- ZANNOFHADGWOLI-UHFFFAOYSA-N ethyl 2-hydroxyacetate Chemical compound CCOC(=O)CO ZANNOFHADGWOLI-UHFFFAOYSA-N 0.000 description 1
- MVUMJYQUKKUOHO-UHFFFAOYSA-N ethyl 3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)C=CN(C)C MVUMJYQUKKUOHO-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 150000002301 glucosamine derivatives Chemical class 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000004140 ketosis Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- LKXKFNITWXCBPD-UHFFFAOYSA-N methyl 2-fluoro-4-(4-propanoyltriazol-2-yl)benzoate Chemical compound CCC(=O)c1cnn(n1)-c1ccc(C(=O)OC)c(F)c1 LKXKFNITWXCBPD-UHFFFAOYSA-N 0.000 description 1
- FHBBCZQHMLGZRZ-UHFFFAOYSA-N methyl 2-fluoro-4-(5-propanoyltetrazol-2-yl)benzoate Chemical compound CCC(=O)c1nnn(n1)-c1ccc(C(=O)OC)c(F)c1 FHBBCZQHMLGZRZ-UHFFFAOYSA-N 0.000 description 1
- NVSXWDKMCKMZFM-UHFFFAOYSA-N methyl 2-fluoro-4-[4-(1-hydroxyethyl)triazol-2-yl]benzoate Chemical compound COC(=O)c1ccc(cc1F)-n1ncc(n1)C(C)O NVSXWDKMCKMZFM-UHFFFAOYSA-N 0.000 description 1
- VFCZFJAISFNHKW-UHFFFAOYSA-N methyl 2-fluoro-4-[4-(1-hydroxypropyl)triazol-2-yl]benzoate Chemical compound CCC(O)c1cnn(n1)-c1ccc(C(=O)OC)c(F)c1 VFCZFJAISFNHKW-UHFFFAOYSA-N 0.000 description 1
- DKIWSNFQMGZNRH-UHFFFAOYSA-N methyl 2-fluoro-4-[5-(1-hydroxyethyl)-1,3-thiazol-2-yl]benzoate Chemical compound COC(=O)c1ccc(cc1F)-c1ncc(s1)C(C)O DKIWSNFQMGZNRH-UHFFFAOYSA-N 0.000 description 1
- PCEPPBWMYAOCQK-UHFFFAOYSA-N methyl 2-fluoro-4-[5-(1-hydroxyethyl)tetrazol-2-yl]benzoate Chemical compound COC(=O)c1ccc(cc1F)-n1nnc(n1)C(C)O PCEPPBWMYAOCQK-UHFFFAOYSA-N 0.000 description 1
- IJDZLTNZVNZLMO-UHFFFAOYSA-N methyl 2-fluoro-4-[5-(1-hydroxypropyl)tetrazol-2-yl]benzoate Chemical compound CCC(O)c1nnn(n1)-c1ccc(C(=O)OC)c(F)c1 IJDZLTNZVNZLMO-UHFFFAOYSA-N 0.000 description 1
- RMFOGONFLMMXKJ-UHFFFAOYSA-N methyl 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]ethyl]-1,3-thiazol-2-yl]-2-fluorobenzoate Chemical compound COC(=O)c1ccc(cc1F)-c1ncc(s1)C(C)Oc1ccc(cc1)C(=O)C1CC1 RMFOGONFLMMXKJ-UHFFFAOYSA-N 0.000 description 1
- AXBMAEDSXAKFHG-UHFFFAOYSA-N methyl 4-[5-[1-[4-(cyclopropanecarbonyl)phenoxy]propyl]tetrazol-2-yl]-2-fluorobenzoate Chemical compound CCC(Oc1ccc(cc1)C(=O)C1CC1)c1nnn(n1)-c1ccc(C(=O)OC)c(F)c1 AXBMAEDSXAKFHG-UHFFFAOYSA-N 0.000 description 1
- JNOZCOHRTZTSMX-UHFFFAOYSA-N methyl 4-amino-2-fluoro-3-(hydroxyiminomethyl)benzoate Chemical compound NC1=C(C(=C(C(=O)OC)C=C1)F)C=NO JNOZCOHRTZTSMX-UHFFFAOYSA-N 0.000 description 1
- ZDCJFYFJXQCBSO-UHFFFAOYSA-N methyl 4-carbamothioyl-2-fluorobenzoate Chemical compound COC(=O)c1ccc(cc1F)C(N)=S ZDCJFYFJXQCBSO-UHFFFAOYSA-N 0.000 description 1
- BTSFXVSAECXZNJ-UHFFFAOYSA-N methyl 4-cyano-2-fluorobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1F BTSFXVSAECXZNJ-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- XXZNFWHGOMHWCO-UHFFFAOYSA-N n,n-diethylthiohydroxylamine Chemical compound CCN(S)CC XXZNFWHGOMHWCO-UHFFFAOYSA-N 0.000 description 1
- QNIJHQFUVWJCDA-UHFFFAOYSA-N n-(diethylaminosulfanyl)-n-ethylethanamine Chemical compound CCN(CC)SN(CC)CC QNIJHQFUVWJCDA-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 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 1
- 238000011160 research Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- ZNKXTIAQRUWLRL-UHFFFAOYSA-M sodium;sulfane;hydroxide Chemical compound O.[Na+].[SH-] ZNKXTIAQRUWLRL-UHFFFAOYSA-M 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical class [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- IRFRILQFZFQVOW-UHFFFAOYSA-N tert-butyl 2-fluoro-4-[4-(1-hydroxyethyl)triazol-2-yl]benzoate Chemical compound CC(O)c1cnn(n1)-c1ccc(C(=O)OC(C)(C)C)c(F)c1 IRFRILQFZFQVOW-UHFFFAOYSA-N 0.000 description 1
- IRFRILQFZFQVOW-VIFPVBQESA-N tert-butyl 2-fluoro-4-[4-[(1S)-1-hydroxyethyl]triazol-2-yl]benzoate Chemical compound C[C@H](O)c1cnn(n1)-c1ccc(C(=O)OC(C)(C)C)c(F)c1 IRFRILQFZFQVOW-VIFPVBQESA-N 0.000 description 1
- JFFDAFMGTAUBML-AWEZNQCLSA-N tert-butyl 2-fluoro-4-[4-[(1S)-1-hydroxypropyl]triazol-2-yl]benzoate Chemical compound CC[C@H](O)c1cnn(n1)-c1ccc(C(=O)OC(C)(C)C)c(F)c1 JFFDAFMGTAUBML-AWEZNQCLSA-N 0.000 description 1
- LXGZCNLIPFDAAM-UHFFFAOYSA-N tert-butyl 4-amino-2-fluoro-3-(hydroxyiminomethyl)benzoate Chemical compound NC1=C(C(=C(C(=O)OC(C)(C)C)C=C1)F)C=NO LXGZCNLIPFDAAM-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical group CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P3/08—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
-
- 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)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012007840 | 2012-01-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201335141A TW201335141A (zh) | 2013-09-01 |
| TWI551590B true TWI551590B (zh) | 2016-10-01 |
Family
ID=48799224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102101765A TWI551590B (zh) | 2012-01-18 | 2013-01-17 | 經取代之苯吖唑衍生物 |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US9233958B2 (enExample) |
| EP (2) | EP3009433B1 (enExample) |
| JP (2) | JP6104181B2 (enExample) |
| KR (1) | KR20140113688A (enExample) |
| CN (1) | CN104159892A (enExample) |
| AU (1) | AU2013210394A1 (enExample) |
| BR (1) | BR112014017656A2 (enExample) |
| CA (1) | CA2861847A1 (enExample) |
| CO (1) | CO7020920A2 (enExample) |
| ES (2) | ES2640667T3 (enExample) |
| HK (2) | HK1200824A1 (enExample) |
| IL (1) | IL233682A0 (enExample) |
| IN (1) | IN2014MN01442A (enExample) |
| MX (1) | MX2014008790A (enExample) |
| NZ (1) | NZ627303A (enExample) |
| PH (1) | PH12014501646A1 (enExample) |
| RU (1) | RU2014133738A (enExample) |
| SG (1) | SG11201404026SA (enExample) |
| TW (1) | TWI551590B (enExample) |
| WO (1) | WO2013108800A1 (enExample) |
| ZA (1) | ZA201405108B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN2014MN01442A (enExample) | 2012-01-18 | 2015-07-03 | Daiichi Sankyo Co Ltd | |
| JP2017119628A (ja) * | 2014-05-09 | 2017-07-06 | 日産化学工業株式会社 | 置換アゾール化合物及び糖尿病治療薬 |
| WO2017104782A1 (ja) * | 2015-12-17 | 2017-06-22 | 第一三共株式会社 | オキサジアゾール化合物の製造方法 |
| EP3766879A1 (en) * | 2019-07-19 | 2021-01-20 | Basf Se | Pesticidal pyrazole derivatives |
| CN111388471B (zh) * | 2020-03-03 | 2021-01-12 | 牡丹江医学院 | 一种治疗胆囊炎的药物及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460493A (zh) * | 2006-04-06 | 2009-06-17 | 普罗西迪恩有限公司 | 杂环g蛋白偶联受体激动剂 |
| TW201107317A (en) * | 2009-08-05 | 2011-03-01 | Daiichi Sankyo Co Ltd | Amide derivatives |
| TW201109322A (en) * | 2009-08-05 | 2011-03-16 | Daiichi Sankyo Co Ltd | Sulfone derivatives |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0029974D0 (en) | 2000-12-08 | 2001-01-24 | Glaxo Group Ltd | Chemical compounds |
| JP4958560B2 (ja) | 2003-12-24 | 2012-06-20 | プロシディオン・リミテッド | Ｇｐｃｒ受容体作動薬としてのヘテロ環誘導体 |
| CN1997633A (zh) * | 2004-05-25 | 2007-07-11 | 麦它波莱克斯股份有限公司 | 作为ppar调节剂的取代的三唑及其制备方法 |
| US20090325924A1 (en) | 2005-06-30 | 2009-12-31 | Stuart Edward | GPCR Agonists |
| MX2007016508A (es) | 2005-06-30 | 2008-03-04 | Prosidion Ltd | Agonistas del receptor acoplado a la proteina g. |
| SI1931660T1 (sl) * | 2005-09-29 | 2012-12-31 | Sanofi | Derivati fenil-(1,2,4)-oksadiazol-5-ona s fenilno skupino, postopki za njihovo pripravo in njihova uporaba kot zdravila |
| NZ571869A (en) * | 2006-04-06 | 2011-11-25 | Prosidion Ltd | Heterocyclic GPCR agonists |
| AU2008279447A1 (en) * | 2007-07-19 | 2009-01-29 | Metabolex, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the RUP3 or GPR119 receptor for the treatment of diabetes and metabolic disorders |
| AU2008312948C1 (en) | 2007-10-16 | 2012-08-09 | Daiichi Sankyo Company, Limited | Pyrimidyl indoline compound |
| EP2241558A1 (en) | 2009-04-03 | 2010-10-20 | Merck Serono SA | Oxadiazole derivatives |
| WO2010119881A1 (ja) | 2009-04-15 | 2010-10-21 | 第一三共株式会社 | インドリン化合物 |
| JP5069813B2 (ja) * | 2010-10-14 | 2012-11-07 | 第一三共株式会社 | アシルベンゼン誘導体 |
| PH12014500251A1 (en) | 2011-07-29 | 2014-03-17 | Daiichi Sankyo Co Ltd | N-hetero-ring-substituted amide derivative |
| IN2014MN01442A (enExample) | 2012-01-18 | 2015-07-03 | Daiichi Sankyo Co Ltd |
-
2013
- 2013-01-17 IN IN1442MUN2014 patent/IN2014MN01442A/en unknown
- 2013-01-17 EP EP15192148.3A patent/EP3009433B1/en not_active Not-in-force
- 2013-01-17 TW TW102101765A patent/TWI551590B/zh not_active IP Right Cessation
- 2013-01-17 JP JP2013554315A patent/JP6104181B2/ja not_active Expired - Fee Related
- 2013-01-17 BR BR112014017656A patent/BR112014017656A2/pt not_active IP Right Cessation
- 2013-01-17 ES ES15192148.3T patent/ES2640667T3/es active Active
- 2013-01-17 CN CN201380014867.6A patent/CN104159892A/zh active Pending
- 2013-01-17 KR KR1020147019737A patent/KR20140113688A/ko not_active Withdrawn
- 2013-01-17 EP EP13738825.2A patent/EP2805941B1/en not_active Not-in-force
- 2013-01-17 HK HK15101292.6A patent/HK1200824A1/en unknown
- 2013-01-17 MX MX2014008790A patent/MX2014008790A/es unknown
- 2013-01-17 RU RU2014133738A patent/RU2014133738A/ru not_active Application Discontinuation
- 2013-01-17 NZ NZ627303A patent/NZ627303A/en not_active IP Right Cessation
- 2013-01-17 WO PCT/JP2013/050710 patent/WO2013108800A1/ja not_active Ceased
- 2013-01-17 CA CA2861847A patent/CA2861847A1/en not_active Abandoned
- 2013-01-17 ES ES13738825.2T patent/ES2602962T3/es active Active
- 2013-01-17 US US14/372,832 patent/US9233958B2/en not_active Expired - Fee Related
- 2013-01-17 AU AU2013210394A patent/AU2013210394A1/en not_active Abandoned
- 2013-01-17 SG SG11201404026SA patent/SG11201404026SA/en unknown
-
2014
- 2014-07-11 ZA ZA2014/05108A patent/ZA201405108B/en unknown
- 2014-07-17 PH PH12014501646A patent/PH12014501646A1/en unknown
- 2014-07-17 IL IL233682A patent/IL233682A0/en unknown
- 2014-07-31 CO CO14166876A patent/CO7020920A2/es unknown
-
2015
- 2015-02-05 HK HK16108406.3A patent/HK1220448A1/en unknown
- 2015-12-01 US US14/956,116 patent/US20160081993A1/en not_active Abandoned
- 2015-12-01 US US14/956,240 patent/US9725438B2/en not_active Expired - Fee Related
-
2016
- 2016-12-20 JP JP2016247095A patent/JP2017052800A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460493A (zh) * | 2006-04-06 | 2009-06-17 | 普罗西迪恩有限公司 | 杂环g蛋白偶联受体激动剂 |
| TW201107317A (en) * | 2009-08-05 | 2011-03-01 | Daiichi Sankyo Co Ltd | Amide derivatives |
| TW201109322A (en) * | 2009-08-05 | 2011-03-16 | Daiichi Sankyo Co Ltd | Sulfone derivatives |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115066418B (zh) | 具有抗炎性质的羧基衍生物 | |
| CN104822661B (zh) | 5‑氨基四氢喹啉‑2‑羧酸及其用途 | |
| JP5988379B2 (ja) | スフィンゴシン−１−リン酸受容体変調因子および不斉合成方法 | |
| TWI551590B (zh) | 經取代之苯吖唑衍生物 | |
| US9480693B2 (en) | Substituted bisphenyl butanoic phosphonic acid derivatives as NEP inhibitors | |
| JP7683930B2 (ja) | セミカルバジド感受性アミンオキシダーゼ阻害剤の調製及びその応用 | |
| US9150505B2 (en) | Prophylactic or therapeutic agent for diabetes or obesity | |
| CN102781910B (zh) | 烷基胺衍生物 | |
| JP2007533723A (ja) | α２δリガンドを含む組合せ | |
| JP5329656B2 (ja) | イミダゾリジン誘導体 | |
| HK1224288A1 (zh) | 作为类糜蛋白酶抑制剂的取代的尿嘧啶 | |
| WO2018157801A1 (zh) | 氰基取代的稠合双环衍生物及其制备方法和用途 | |
| CN102574823B (zh) | 酰胺衍生物 | |
| AU2014216417B2 (en) | Substituted bisphenyl butanoic acid derivatives as NEP inhibitors with improved in vivo efficacy | |
| US20240317764A1 (en) | Salts and solid forms of a compound having apj receptor activity | |
| US11426375B2 (en) | Substituted bisphenyl butanoic ester derivatives as NEP inhibitors | |
| RU2784522C2 (ru) | Замещенные производные бисфенилового эфира масляной кислоты в качестве ингибиторов NEP | |
| BR122025013926A2 (pt) | Ácidos carboxílicos de pirazolo piperidina substituídos, seu processo de preparação e medicamento | |
| HK40011866A (en) | Substituted bisphenyl butanoic ester derivatives as nep inhibitors | |
| HK40011866B (en) | Substituted bisphenyl butanoic ester derivatives as nep inhibitors | |
| JP2005097236A (ja) | エラスターゼ遊離抑制剤及び脳梗塞治療薬 | |
| WO2011105099A1 (ja) | 新規な４－アルコキシピリミジン構造を有する化合物及びこれを含有する医薬 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |