NO312160B1 - Propionsyrederivater og farmasöytiske sammensetninger inneholdende disse - Google Patents

Propionsyrederivater og farmasöytiske sammensetninger inneholdende disse Download PDF

Info

Publication number: NO312160B1
Authority: NO; Norway
Prior art keywords: phenyl; methyl; ethoxy; oxazolyl; alkyl
Prior art date: 1996-08-19

Application number

NO19990700A

Other languages

English (en)

Norwegian (no)

Other versions

NO990700D0 (no

NO990700L (no

Inventor

Hisashi Shinkai

Tsutomu Shibata

Satoshi Ohrui

Original Assignee

Japan Tobacco Inc

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

1996-08-19

Filing date

1999-02-15

Publication date

2002-04-02

1996-08-19 Priority claimed from JP21754896A external-priority patent/JP3215048B2/ja

1999-02-15 Application filed by Japan Tobacco Inc filed Critical Japan Tobacco Inc

1999-02-15 Publication of NO990700D0 publication Critical patent/NO990700D0/no

1999-04-19 Publication of NO990700L publication Critical patent/NO990700L/no

2002-04-02 Publication of NO312160B1 publication Critical patent/NO312160B1/no

Links

150000005599 propionic acid derivatives Chemical class 0.000 title claims description 19
239000008194 pharmaceutical composition Substances 0.000 title claims description 13
229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 title description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 68
-1 hydroxy, carboxy Chemical group 0.000 claims description 62
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
206010012601 diabetes mellitus Diseases 0.000 claims description 14
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
NNIZTTLESROFOP-UHFFFAOYSA-N 3-methoxy-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound C1=CC(CC(C(=O)OC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 NNIZTTLESROFOP-UHFFFAOYSA-N 0.000 claims description 11
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
125000004430 oxygen atom Chemical group O* 0.000 claims description 9
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 9
239000004202 carbamide Substances 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
TZCIFDUMMAMGNA-UHFFFAOYSA-N 3-amino-2-methyl-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CC(C)(C(N)=O)C(O)=O)C=C1 TZCIFDUMMAMGNA-UHFFFAOYSA-N 0.000 claims description 5
QXWXIDGJCWEJRO-UHFFFAOYSA-N methyl 3-(methoxycarbonylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)NC(=O)OC)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 QXWXIDGJCWEJRO-UHFFFAOYSA-N 0.000 claims description 5
RDJAJUMKENHBEB-UHFFFAOYSA-N methyl 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 RDJAJUMKENHBEB-UHFFFAOYSA-N 0.000 claims description 5
229940124597 therapeutic agent Drugs 0.000 claims description 5
JBKCNYIGGZDDPC-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CC(C(O)=O)C(O)=O)C=C1 JBKCNYIGGZDDPC-UHFFFAOYSA-N 0.000 claims description 4
CPZMHJMRORYGMJ-UHFFFAOYSA-N 3-methoxy-2-methyl-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound C1=CC(CC(C)(C(=O)OC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 CPZMHJMRORYGMJ-UHFFFAOYSA-N 0.000 claims description 4
DZVHQKHVUZVQOO-UHFFFAOYSA-N 3-o-tert-butyl 1-o-methyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C(=O)OC)C(=O)OC(C)(C)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 DZVHQKHVUZVQOO-UHFFFAOYSA-N 0.000 claims description 4
GNXHZXFHJQWEMB-UHFFFAOYSA-N diethyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C(=O)OCC)C(=O)OCC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 GNXHZXFHJQWEMB-UHFFFAOYSA-N 0.000 claims description 4
ASNRDWDICLZVLR-UHFFFAOYSA-N methyl 3-amino-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)OC)C(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ASNRDWDICLZVLR-UHFFFAOYSA-N 0.000 claims description 4
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
HSYJCVSKFIYZKH-UHFFFAOYSA-N 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CCC(N)=O)C=C1 HSYJCVSKFIYZKH-UHFFFAOYSA-N 0.000 claims description 3
ZXFXZLXIYYLMAV-UHFFFAOYSA-N methyl 3-amino-2-methyl-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C)(C(=O)OC)C(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZXFXZLXIYYLMAV-UHFFFAOYSA-N 0.000 claims description 3
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
HIPDMTKLZWUFGS-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxo-3-phenylmethoxypropanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(O)=O)C(=O)OCC1=CC=CC=C1 HIPDMTKLZWUFGS-UHFFFAOYSA-N 0.000 claims description 2
OTGJWKIOJGCFGG-UHFFFAOYSA-N 3-o-tert-butyl 1-o-methyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]propanedioate Chemical compound C1=CC(C=C(C(=O)OC)C(=O)OC(C)(C)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 OTGJWKIOJGCFGG-UHFFFAOYSA-N 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
ZLCATJPZUHXLDD-UHFFFAOYSA-N methyl n-[3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]carbamate Chemical compound C1=CC(CCC(=O)NC(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZLCATJPZUHXLDD-UHFFFAOYSA-N 0.000 claims description 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 2
125000001589 carboacyl group Chemical group 0.000 claims 2
150000001875 compounds Chemical class 0.000 description 194
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
239000000203 mixture Substances 0.000 description 88
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 86
239000002904 solvent Substances 0.000 description 82
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 73
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 69
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
238000005160 1H NMR spectroscopy Methods 0.000 description 59
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 59
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
238000000034 method Methods 0.000 description 49
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
239000007787 solid Substances 0.000 description 47
238000010438 heat treatment Methods 0.000 description 46
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 44
239000000243 solution Substances 0.000 description 44
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 42
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 38
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 38
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 38
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 37
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 34
238000010898 silica gel chromatography Methods 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 30
238000004519 manufacturing process Methods 0.000 description 29
239000012044 organic layer Substances 0.000 description 26
239000003921 oil Substances 0.000 description 25
235000019198 oils Nutrition 0.000 description 25
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
229910052943 magnesium sulfate Inorganic materials 0.000 description 22
235000019341 magnesium sulphate Nutrition 0.000 description 22
239000003960 organic solvent Substances 0.000 description 22
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
101150041968 CDC13 gene Proteins 0.000 description 21
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 21
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 20
239000007858 starting material Substances 0.000 description 20
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 19
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 19
150000004945 aromatic hydrocarbons Chemical class 0.000 description 19
150000008282 halocarbons Chemical class 0.000 description 19
229930195733 hydrocarbon Natural products 0.000 description 19
150000002430 hydrocarbons Chemical class 0.000 description 19
239000002798 polar solvent Substances 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
239000008096 xylene Substances 0.000 description 19
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 18
150000002170 ethers Chemical class 0.000 description 18
239000003054 catalyst Substances 0.000 description 17
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 16
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
150000002148 esters Chemical class 0.000 description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
238000001914 filtration Methods 0.000 description 13
230000002218 hypoglycaemic effect Effects 0.000 description 13
229910001867 inorganic solvent Inorganic materials 0.000 description 13
239000003049 inorganic solvent Substances 0.000 description 13
150000002576 ketones Chemical class 0.000 description 13
238000010992 reflux Methods 0.000 description 13
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 12
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 12
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 12
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 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
239000012046 mixed solvent Substances 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
238000003756 stirring Methods 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 11
150000001298 alcohols Chemical class 0.000 description 11
239000008103 glucose Substances 0.000 description 11
239000000126 substance Substances 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
239000013078 crystal Substances 0.000 description 10
239000010410 layer Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
239000012298 atmosphere Substances 0.000 description 9
GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 9
239000000843 powder Substances 0.000 description 9
239000012312 sodium hydride Substances 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
239000005909 Kieselgur Substances 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
OKDCTIYZEDHHSM-UHFFFAOYSA-N dimethyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C(=O)OC)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 OKDCTIYZEDHHSM-UHFFFAOYSA-N 0.000 description 8
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
239000002253 acid Substances 0.000 description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
102000004877 Insulin Human genes 0.000 description 6
108090001061 Insulin Proteins 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
238000000921 elemental analysis Methods 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
229940125396 insulin Drugs 0.000 description 6
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
238000005192 partition Methods 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
VFLDEIGTSMXRGM-UHFFFAOYSA-N 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CCC(O)=O)C=C1 VFLDEIGTSMXRGM-UHFFFAOYSA-N 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
IPWZPTYWJHXUHD-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C=C1 IPWZPTYWJHXUHD-UHFFFAOYSA-N 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 4
206010022489 Insulin Resistance Diseases 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
235000005911 diet Nutrition 0.000 description 4
230000037213 diet Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 4
239000012091 fetal bovine serum Substances 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000002808 molecular sieve Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
229910003446 platinum oxide Inorganic materials 0.000 description 4
238000000926 separation method Methods 0.000 description 4
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000011282 treatment Methods 0.000 description 4
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
BLFBXXLOJJBXAP-UHFFFAOYSA-N 1-o-[(4-nitrophenyl)methyl] 3-o-propan-2-yl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]propanedioate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1COC(=O)C(C(=O)OC(C)C)=CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 BLFBXXLOJJBXAP-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 3
229910001863 barium hydroxide Inorganic materials 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
230000005587 bubbling Effects 0.000 description 3
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
230000000269 nucleophilic effect Effects 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 3
229910000342 sodium bisulfate Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
MJAMNJNCEOHYIU-UHFFFAOYSA-N 1,2-oxazolidine-3,4-dione Chemical class O=C1CONC1=O MJAMNJNCEOHYIU-UHFFFAOYSA-N 0.000 description 2
XNIZEPDJMWFNLF-UHFFFAOYSA-N 1-o,1-o-dibenzyl 2-o-ethyl 1-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]ethane-1,1,2-tricarboxylate Chemical compound C=1C=CC=CC=1COC(=O)C(C(=O)OCC=1C=CC=CC=1)(CC(=O)OCC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 XNIZEPDJMWFNLF-UHFFFAOYSA-N 0.000 description 2
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
YFMXYENCOLNECJ-UHFFFAOYSA-N 2-(2-ethoxy-2-oxoethyl)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioic acid Chemical compound C1=CC(CC(CC(=O)OCC)(C(O)=O)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 YFMXYENCOLNECJ-UHFFFAOYSA-N 0.000 description 2
ZNIPPVFZUQHMAV-UHFFFAOYSA-N 2-hydroxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CC(O)C(N)=O)C=C1 ZNIPPVFZUQHMAV-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
QPQAGTXTUAWTHX-UHFFFAOYSA-N 3-[4-[2-[2-(1-benzothiophen-2-yl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2SC3=CC=CC=C3C=2)=NC=1CCOC1=CC=C(CCC(O)=O)C=C1 QPQAGTXTUAWTHX-UHFFFAOYSA-N 0.000 description 2
FAWBLKSFJWSWAT-UHFFFAOYSA-N 3-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]pentane-2,4-dione Chemical compound C1=CC(CC(C(=O)C)C(C)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 FAWBLKSFJWSWAT-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
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
206010003210 Arteriosclerosis Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
229940123208 Biguanide Drugs 0.000 description 2
101000957724 Catostomus commersonii Corticoliberin-1 Proteins 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
208000031226 Hyperlipidaemia Diseases 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
XBJFCYDKBDVADW-UHFFFAOYSA-N acetonitrile;formic acid Chemical compound CC#N.OC=O XBJFCYDKBDVADW-UHFFFAOYSA-N 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
208000011775 arteriosclerosis disease Diseases 0.000 description 2
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 2
150000004283 biguanides Chemical class 0.000 description 2
230000037396 body weight Effects 0.000 description 2
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
XFAFMBXJAMRRRL-UHFFFAOYSA-N dibenzyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 XFAFMBXJAMRRRL-UHFFFAOYSA-N 0.000 description 2
150000005690 diesters Chemical class 0.000 description 2
ZRUXJQGGZSWJFF-UHFFFAOYSA-N diethyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]propanedioate Chemical compound C1=CC(C=C(C(=O)OCC)C(=O)OCC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZRUXJQGGZSWJFF-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
MGLYLNYVOBRDIF-UHFFFAOYSA-N dipropan-2-yl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]propanedioate Chemical compound C1=CC(C=C(C(=O)OC(C)C)C(=O)OC(C)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 MGLYLNYVOBRDIF-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
BSJSLCICSGGJBX-UHFFFAOYSA-N ethyl 2-acetamido-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=CC(CC(C(=O)OCC)NC(C)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 BSJSLCICSGGJBX-UHFFFAOYSA-N 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
201000005577 familial hyperlipidemia Diseases 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
230000000055 hyoplipidemic effect Effects 0.000 description 2
230000003345 hyperglycaemic effect Effects 0.000 description 2
230000000871 hypocholesterolemic effect Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910052744 lithium Inorganic materials 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
GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
GUZOYDCKWDWUEK-UHFFFAOYSA-N methyl 2-hydroxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=CC(CC(O)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 GUZOYDCKWDWUEK-UHFFFAOYSA-N 0.000 description 2
XRAMJHXWXCMGJM-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)propionate Chemical compound COC(=O)CCC1=CC=C(O)C=C1 XRAMJHXWXCMGJM-UHFFFAOYSA-N 0.000 description 2
JCXVBXZHHNRTJV-UHFFFAOYSA-N methyl 3-(methylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)NC)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JCXVBXZHHNRTJV-UHFFFAOYSA-N 0.000 description 2
MZUKOSDEEXNJGL-UHFFFAOYSA-N methyl 3-[4-[2-[2-(1-benzothiophen-2-yl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCCC1=C(C)OC(C=2SC3=CC=CC=C3C=2)=N1 MZUKOSDEEXNJGL-UHFFFAOYSA-N 0.000 description 2
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
XVDBWWRIXBMVJV-UHFFFAOYSA-N n-[bis(dimethylamino)phosphanyl]-n-methylmethanamine Chemical compound CN(C)P(N(C)C)N(C)C XVDBWWRIXBMVJV-UHFFFAOYSA-N 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 2
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
125000004742 propyloxycarbonyl group Chemical group 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
238000000638 solvent extraction Methods 0.000 description 2
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
PAHVTLRWCQYFEB-UHFFFAOYSA-N 1,2-oxazolidine-3,5-dione Chemical compound O=C1CC(=O)ON1 PAHVTLRWCQYFEB-UHFFFAOYSA-N 0.000 description 1
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
CMEPUAROFJSGJN-UHFFFAOYSA-N 1,4-dioxan-2-ylmethanol Chemical compound OCC1COCCO1 CMEPUAROFJSGJN-UHFFFAOYSA-N 0.000 description 1
PTLJCUMPQNQCKI-UHFFFAOYSA-N 1-o-[(4-nitrophenyl)methyl] 3-o-propan-2-yl propanedioate Chemical compound CC(C)OC(=O)CC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 PTLJCUMPQNQCKI-UHFFFAOYSA-N 0.000 description 1
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
QGNITQXBLBMGSS-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl 4-methylbenzenesulfonate Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOS(=O)(=O)C1=CC=C(C)C=C1 QGNITQXBLBMGSS-UHFFFAOYSA-N 0.000 description 1
UIEKGRPIYJDYGY-UHFFFAOYSA-N 2-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=CC=C1C=O UIEKGRPIYJDYGY-UHFFFAOYSA-N 0.000 description 1
KGBDITNOAXHCAE-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxo-3-phenoxypropanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(O)=O)C(=O)OC1=CC=CC=C1 KGBDITNOAXHCAE-UHFFFAOYSA-N 0.000 description 1
IIHKRGNXMPKYTP-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxo-3-propan-2-yloxypropanoic acid Chemical compound C1=CC(CC(C(=O)OC(C)C)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IIHKRGNXMPKYTP-UHFFFAOYSA-N 0.000 description 1
RIBNEGZRJCBFHK-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1=CC=CC=C1C=O RIBNEGZRJCBFHK-UHFFFAOYSA-N 0.000 description 1
IAYSZFMDKTUMLT-UHFFFAOYSA-N 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanediamide Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CC(C(N)=O)C(N)=O)C=C1 IAYSZFMDKTUMLT-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
ISDGWTZFJKFKMO-UHFFFAOYSA-N 2-phenyl-1,3-dioxane-4,6-dione Chemical compound O1C(=O)CC(=O)OC1C1=CC=CC=C1 ISDGWTZFJKFKMO-UHFFFAOYSA-N 0.000 description 1
APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
ZXWRLTUPYHDAHO-UHFFFAOYSA-N 3-(dimethylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound C1=CC(CC(C(=O)N(C)C)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZXWRLTUPYHDAHO-UHFFFAOYSA-N 0.000 description 1
WEWLGXSKFUTOOD-UHFFFAOYSA-N 3-(methylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound C1=CC(CC(C(=O)NC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 WEWLGXSKFUTOOD-UHFFFAOYSA-N 0.000 description 1
JUNDOMQFXBAZTQ-UHFFFAOYSA-N 3-[4-[2-[2-(1-benzothiophen-2-yl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]-n-carbamoylpropanamide Chemical compound CC=1OC(C=2SC3=CC=CC=C3C=2)=NC=1CCOC1=CC=C(CCC(=O)NC(N)=O)C=C1 JUNDOMQFXBAZTQ-UHFFFAOYSA-N 0.000 description 1
XGDVDMCKNUYLJY-UHFFFAOYSA-N 3-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]pentane-2,4-dione Chemical compound C1=CC(C=C(C(=O)C)C(C)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 XGDVDMCKNUYLJY-UHFFFAOYSA-N 0.000 description 1
ZXILSYIHBWBPKO-UHFFFAOYSA-N 3-amino-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CC(C(N)=O)C(O)=O)C=C1 ZXILSYIHBWBPKO-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
KHIBBMKEFBUJIP-UHFFFAOYSA-N 3-ethoxy-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoic acid Chemical compound C1=CC(CC(C(=O)OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 KHIBBMKEFBUJIP-UHFFFAOYSA-N 0.000 description 1
BGQQTGDUIHUHFJ-UHFFFAOYSA-N 3-o-benzyl 1-o-tert-butyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(=O)OC(C)(C)C)C(=O)OCC1=CC=CC=C1 BGQQTGDUIHUHFJ-UHFFFAOYSA-N 0.000 description 1
XPSYZCWYRWHVCC-UHFFFAOYSA-N 3-o-tert-butyl 1-o-methyl propanedioate Chemical compound COC(=O)CC(=O)OC(C)(C)C XPSYZCWYRWHVCC-UHFFFAOYSA-N 0.000 description 1
NTSWGSRJHHXHBB-UHFFFAOYSA-N 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde Chemical compound N1=CC(CC)=CC=C1CCOC1=CC=C(C=O)C=C1 NTSWGSRJHHXHBB-UHFFFAOYSA-N 0.000 description 1
QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 1
OJNLESCEMIHAKU-UHFFFAOYSA-N 4-ethoxy-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-4-oxobutanoic acid Chemical compound C1=CC(CC(CC(=O)OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 OJNLESCEMIHAKU-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
CMRCIXWECVAGOS-UHFFFAOYSA-N C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C[NH3+].C[NH3+].C[NH3+].C[NH3+] Chemical compound C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C[NH3+].C[NH3+].C[NH3+].C[NH3+] CMRCIXWECVAGOS-UHFFFAOYSA-N 0.000 description 1
SXZLEYQTCLJLAO-XYOKQWHBSA-N C1=CC(/C=C/C(=O)OCC)=CC=C1OCCC1=CC=C(CC)C=N1 Chemical compound C1=CC(/C=C/C(=O)OCC)=CC=C1OCCC1=CC=C(CC)C=N1 SXZLEYQTCLJLAO-XYOKQWHBSA-N 0.000 description 1
RVDGDDSJAJBCPF-UHFFFAOYSA-N C1=CC(CC(OC)C(O)=O)=CC=C1OCCC1(C=2C=CC=CC=2)C(C)OC(C=2C=CC=CC=2)=N1 Chemical compound C1=CC(CC(OC)C(O)=O)=CC=C1OCCC1(C=2C=CC=CC=2)C(C)OC(C=2C=CC=CC=2)=N1 RVDGDDSJAJBCPF-UHFFFAOYSA-N 0.000 description 1
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
241000725101 Clea Species 0.000 description 1
208000002249 Diabetes Complications Diseases 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102000005548 Hexokinase Human genes 0.000 description 1
108700040460 Hexokinases Proteins 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical class NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
239000004166 Lanolin Substances 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 1
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
REYULYDIUUAQQJ-UHFFFAOYSA-N [1-amino-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-1-oxopropan-2-yl] methyl carbonate Chemical compound C1=CC(CC(OC(=O)OC)C(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 REYULYDIUUAQQJ-UHFFFAOYSA-N 0.000 description 1
JQSIHOWVTRFFNR-UHFFFAOYSA-N [NH4+].[NH4+].C=C.CC([O-])=O.CC([O-])=O Chemical compound [NH4+].[NH4+].C=C.CC([O-])=O.CC([O-])=O JQSIHOWVTRFFNR-UHFFFAOYSA-N 0.000 description 1
TXVBVQZKWWCOQS-UHFFFAOYSA-N [carbamoyl-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]amino] methyl carbonate Chemical compound C1=CC(CN(OC(=O)OC)C(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 TXVBVQZKWWCOQS-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
229960001466 acetohexamide Drugs 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
239000003472 antidiabetic agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000001483 arginine derivatives Chemical class 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
OHDBYQSGLSTIHF-UHFFFAOYSA-N benzenesulfonic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.OS(=O)(=O)C1=CC=CC=C1 OHDBYQSGLSTIHF-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
229960004111 buformin Drugs 0.000 description 1
XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229960001761 chlorpropamide Drugs 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
SYZWSSNHPZXGML-UHFFFAOYSA-N dichloromethane;oxolane Chemical compound ClCCl.C1CCOC1 SYZWSSNHPZXGML-UHFFFAOYSA-N 0.000 description 1
VCEAZZKRWRQVMM-UHFFFAOYSA-N dimethyl 2-[[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound N1=CC(CC)=CC=C1CCOC1=CC=C(CC(C(=O)OC)C(=O)OC)C=C1 VCEAZZKRWRQVMM-UHFFFAOYSA-N 0.000 description 1
BQXKKHXSEHNGNC-UHFFFAOYSA-N dimethyl 2-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C(=O)OC)C(=O)OC)=CC=C1OCCN(C)C1=NC2=CC=CC=C2O1 BQXKKHXSEHNGNC-UHFFFAOYSA-N 0.000 description 1
BBDCAYJIDVGXMI-UHFFFAOYSA-N dimethyl 2-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methylidene]propanedioate Chemical compound C1=CC(C=C(C(=O)OC)C(=O)OC)=CC=C1OCCN(C)C1=NC2=CC=CC=C2O1 BBDCAYJIDVGXMI-UHFFFAOYSA-N 0.000 description 1
XGLZEYNIINWSBM-UHFFFAOYSA-N dimethyl 2-methyl-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C)(C(=O)OC)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 XGLZEYNIINWSBM-UHFFFAOYSA-N 0.000 description 1
BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
JOPJMFBWLJSLIV-UHFFFAOYSA-N diphenyl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(=O)OC=1C=CC=CC=1)C(=O)OC1=CC=CC=C1 JOPJMFBWLJSLIV-UHFFFAOYSA-N 0.000 description 1
VPTDSXNMNNOEOK-UHFFFAOYSA-N dipropan-2-yl 2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanedioate Chemical compound C1=CC(CC(C(=O)OC(C)C)C(=O)OC(C)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 VPTDSXNMNNOEOK-UHFFFAOYSA-N 0.000 description 1
QRVSDVDFJFKYKA-UHFFFAOYSA-N dipropan-2-yl propanedioate Chemical compound CC(C)OC(=O)CC(=O)OC(C)C QRVSDVDFJFKYKA-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
YBOCPIPIEACROT-UHFFFAOYSA-N ethyl 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]prop-2-enoate Chemical compound C1=CC(C=CC(=O)OCC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 YBOCPIPIEACROT-UHFFFAOYSA-N 0.000 description 1
JZZUDTLMZGTDJG-UHFFFAOYSA-N ethyl 4-amino-3-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-4-oxobutanoate Chemical compound C1=CC(CC(CC(=O)OCC)C(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JZZUDTLMZGTDJG-UHFFFAOYSA-N 0.000 description 1
GMMPSBYOOIPGLX-UHFFFAOYSA-N ethyl 4-methyl-3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)benzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C(C2=C(OC(=N2)C=2C=CC=CC=2)C)=C1 GMMPSBYOOIPGLX-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229960004580 glibenclamide Drugs 0.000 description 1
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
235000013773 glyceryl triacetate Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
229940126904 hypoglycaemic agent Drugs 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910017053 inorganic salt Inorganic materials 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
238000002643 kinesiotherapy Methods 0.000 description 1
208000006443 lactic acidosis Diseases 0.000 description 1
239000008101 lactose Substances 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
YAFLOSKTKCIWIY-UHFFFAOYSA-L magnesium;2-[(4-nitrophenyl)methyl]propanedioate Chemical compound [Mg+2].[O-]C(=O)C(C([O-])=O)CC1=CC=C([N+]([O-])=O)C=C1 YAFLOSKTKCIWIY-UHFFFAOYSA-L 0.000 description 1
239000002609 medium Substances 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
229960003105 metformin Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
PDFUCDWETSQSSU-UHFFFAOYSA-N methyl 2-hydroxy-3-(4-hydroxyphenyl)propanoate Chemical compound COC(=O)C(O)CC1=CC=C(O)C=C1 PDFUCDWETSQSSU-UHFFFAOYSA-N 0.000 description 1
WWBNSQMTESTFSW-UHFFFAOYSA-N methyl 3-(carbamoylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)OC)C(=O)NC(N)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 WWBNSQMTESTFSW-UHFFFAOYSA-N 0.000 description 1
SZUUXWUTACDXJV-UHFFFAOYSA-N methyl 3-(dimethylamino)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)OC)C(=O)N(C)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 SZUUXWUTACDXJV-UHFFFAOYSA-N 0.000 description 1
QWLFBOLAWODIRH-UHFFFAOYSA-N methyl 3-acetamido-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-oxopropanoate Chemical compound C1=CC(CC(C(=O)OC)C(=O)NC(C)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 QWLFBOLAWODIRH-UHFFFAOYSA-N 0.000 description 1
PDFUCDWETSQSSU-SECBINFHSA-N methyl 4-hydroxyphenyllactate Natural products COC(=O)[C@H](O)CC1=CC=C(O)C=C1 PDFUCDWETSQSSU-SECBINFHSA-N 0.000 description 1
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
VYHVQEYOFIYNJP-UHFFFAOYSA-N methyl thiocyanate Chemical compound CSC#N VYHVQEYOFIYNJP-UHFFFAOYSA-N 0.000 description 1
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
MZVYSWVJXQYPOT-UHFFFAOYSA-N methylsulfanylimino(oxo)methane Chemical compound CSN=C=O MZVYSWVJXQYPOT-UHFFFAOYSA-N 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
VTULRCLRCXBMAT-UHFFFAOYSA-N n,n'-dimethyl-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]propanediamide Chemical compound C1=CC(CC(C(=O)NC)C(=O)NC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 VTULRCLRCXBMAT-UHFFFAOYSA-N 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
XXLZLCJPJMSFIO-UHFFFAOYSA-N n-acetyl-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide Chemical compound C1=CC(CCC(=O)NC(=O)C)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 XXLZLCJPJMSFIO-UHFFFAOYSA-N 0.000 description 1
229960001682 n-acetyltyrosine Drugs 0.000 description 1
MFCBOLYRPHTAIG-UHFFFAOYSA-N n-carbamoyl-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(CCC(=O)NC(N)=O)C=C1 MFCBOLYRPHTAIG-UHFFFAOYSA-N 0.000 description 1
125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000002667 nucleating agent Substances 0.000 description 1
229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000001475 oxazolidinediones Chemical class 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
229960003243 phenformin Drugs 0.000 description 1
ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229960005095 pioglitazone Drugs 0.000 description 1
RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000003340 retarding agent Substances 0.000 description 1
239000000523 sample Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000002195 soluble material Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000001467 thiazolidinediones Chemical class 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
229960005371 tolbutamide Drugs 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
229960002622 triacetin Drugs 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
- C07D213/20—Quaternary compounds thereof
- 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
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Endocrinology (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO19990700A 1996-08-19 1999-02-15 Propionsyrederivater og farmasöytiske sammensetninger inneholdende disse NO312160B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP21754896A JP3215048B2 (ja)	1996-04-03	1996-08-19	プロピオン酸誘導体及びその用途
PCT/JP1997/002873 WO1998007699A1 (fr)	1996-08-19	1997-08-19	Derives d'acide propionique et applications de ces derives

Publications (3)

Publication Number	Publication Date
NO990700D0 NO990700D0 (no)	1999-02-15
NO990700L NO990700L (no)	1999-04-19
NO312160B1 true NO312160B1 (no)	2002-04-02

Family

ID=16705991

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19990700A NO312160B1 (no)	1996-08-19	1999-02-15	Propionsyrederivater og farmasöytiske sammensetninger inneholdende disse

Country Status (17)

Country	Link
US (1)	US6204277B1 (ko)
EP (1)	EP0930299A1 (ko)
KR (1)	KR20000068151A (ko)
CN (1)	CN1233241A (ko)
AU (1)	AU740444B2 (ko)
BG (1)	BG103268A (ko)
BR (1)	BR9711627A (ko)
CA (1)	CA2263721A1 (ko)
CZ (1)	CZ53699A3 (ko)
EE (1)	EE03765B1 (ko)
IL (1)	IL128600A0 (ko)
NO (1)	NO312160B1 (ko)
NZ (1)	NZ334738A (ko)
PL (1)	PL331861A1 (ko)
RU (1)	RU2174121C2 (ko)
SK (1)	SK21099A3 (ko)
WO (1)	WO1998007699A1 (ko)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0925063A4 (en) *	1996-07-01	2000-12-27	Lilly Co Eli	Blood-glucose-lowering and lipid-lowering compounds
US6410585B1 (en)	1997-08-28	2002-06-25	Scott D. Larsen	Inhibitors of protein tyrosine phosphatase
DE69824433D1 (en)	1997-08-28	2004-07-15	Biovitrum Ab	Proteintyrosinphosphatase inhibitoren
JP4345230B2 (ja)	1998-03-10	2009-10-14	小野薬品工業株式会社	カルボン酸誘導体およびその誘導体を有効成分として含有する薬剤
GB9817118D0 (en) *	1998-08-07	1998-10-07	Glaxo Group Ltd	Pharmaceutical compounds
AU1857600A (en) *	1998-12-22	2000-07-12	Neurosearch A/S	Ion channel modulating agents
GB9914977D0 (en) *	1999-06-25	1999-08-25	Glaxo Group Ltd	Chemical compounds
US6417212B1 (en)	1999-08-27	2002-07-09	Eli Lilly & Company	Modulators of peroxisome proliferator activated receptors
JP4316787B2 (ja) *	2000-01-11	2009-08-19	壽製薬株式会社	エーテル又はアミド誘導体、その製法並びにそれを含有する糖尿病治療剤、
US6958355B2 (en)	2000-04-24	2005-10-25	Aryx Therapeutics, Inc.	Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US6768008B2 (en) *	2000-04-24	2004-07-27	Aryx Therapeutics	Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US6680387B2 (en)	2000-04-24	2004-01-20	Aryx Therapeutics	Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US7049342B2 (en)	2000-05-29	2006-05-23	Kyorin Pharmaceutical Co., Ltd.	Substituted phenylpropionic acid derivatives
PT1285908E (pt) *	2000-05-29	2008-12-04	Kyorin Seiyaku Kk	Derivados do ácido fenilpropiónico substituídos
US6525095B1 (en) *	2000-07-10	2003-02-25	New Mexico State University Technology Transfer Corporation	Propionate feed supplement
EP1313715B1 (en)	2000-08-23	2007-08-01	Eli Lilly And Company	Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists
CA2418104A1 (en) *	2000-08-23	2002-02-28	Eli Lilly And Company	Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists
AU2001284660A1 (en) *	2000-08-23	2002-03-04	Eli Lilly And Company	Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists
AU2001294673A1 (en)	2000-09-21	2002-04-02	Aryx Therapeutics	Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis
GB0031109D0 (en)	2000-12-20	2001-01-31	Glaxo Group Ltd	Chemical compounds
GB0113231D0 (en) *	2001-05-31	2001-07-25	Glaxo Group Ltd	Chemical compounds
KR100474137B1 (ko) *	2001-11-16	2005-03-08	(주)바이오뉴트리젠	신규의 아릴프로피온산 유도체 및 이를 포함하는 당뇨병 예방 또는 치료용 조성물
KR100459917B1 (ko) *	2001-12-14	2004-12-03	(주)바이오뉴트리젠	페놀릭산 유도체 및 이를 포함하는 혈중 지질 농도 관련질환의 예방 및 치료용 조성물
ITRM20020016A1 (it) *	2002-01-15	2003-07-15	Sigma Tau Ind Farmaceuti	Derivati di acidi fenil(alchil)carbossilici e derivati fenilalchileterociclici dionici, loro uso come medicamenti ad attivita' ipoglicemizza
JP3884736B2 (ja) *	2002-01-17	2007-02-21	トーアエイヨー株式会社	ハロゲノベンジルアミノプロピオン酸誘導体
US20050084840A1 (en) *	2002-01-23	2005-04-21	Hideki Endoh	Method for screening drug for improving insulin resistance
AU2003217274A1 (en) *	2002-02-25	2003-09-09	Eli Lilly And Company	Peroxisome proliferator activated receptor modulators
DE60324898D1 (de)	2002-02-25	2009-01-08	Lilly Co Eli	Modulatoren von peroxisome proliferator-aktivierten rezeptoren
US20030207924A1 (en) *	2002-03-07	2003-11-06	Xue-Min Cheng	Compounds that modulate PPAR activity and methods of preparation
US6833380B2 (en)	2002-03-07	2004-12-21	Warner-Lambert Company, Llc	Compounds that modulate PPAR activity and methods of preparation
US6875780B2 (en)	2002-04-05	2005-04-05	Warner-Lambert Company	Compounds that modulate PPAR activity and methods for their preparation
US6716842B2 (en) *	2002-04-05	2004-04-06	Warner-Lambert Company, Llc	Antidiabetic agents
KR100474202B1 (ko) *	2002-05-04	2005-03-08	강헌중	티아졸 유도체의 제조방법 및 이를 제조하기 위한 중간체
US20060142277A1 (en) *	2002-11-15	2006-06-29	Cadila Healthcare Limited	Substituted aralkyl derivatives
US7244763B2 (en)	2003-04-17	2007-07-17	Warner Lambert Company Llc	Compounds that modulate PPAR activity and methods of preparation
US7037384B2 (en) *	2003-06-23	2006-05-02	Bulk Chemicals, Inc.	Lubricating chemical coating for metalworking
CN100436430C (zh) *	2004-05-24	2008-11-26	北京摩力克科技有限公司	作为hPPARα和hPPARγ激动剂的烷酰基取代的酪氨酸衍生物
NZ552501A (en) *	2004-08-11	2010-03-26	Kyorin Seiyaku Kk	Novel cyclic aminobenzoic acid derivative
FR2882359A1 (fr) *	2005-02-24	2006-08-25	Negma Lerads Soc Par Actions S	Derives activateurs de ppar, procede de preparation et application en therapeutique
FR2901792A1 (fr) *	2006-06-06	2007-12-07	Negma Lerads Soc Par Actions S	DERIVES ACTIVATEURS DE PPARs, PROCEDE DE PREPARATION ET APPLICATION EN THERAPEUTIQUE
KR101497577B1 (ko) *	2012-07-31	2015-03-02	서울대학교산학협력단	2-에톡시프로피온산 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 일주기 연관성 질환의 예방 또는 치료용 약학적 조성물

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1003445B (zh)	1984-10-03	1989-03-01	武田药品工业株式会社	噻唑烷二酮衍生物，其制备方法和用途
US5089514A (en)	1990-06-14	1992-02-18	Pfizer Inc.	3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents
US5334604A (en)	1990-08-23	1994-08-02	Pfizer Inc.	Hypoglycemic hydroxyurea derivatives
US5498621A (en)	1992-05-01	1996-03-12	Pfizer Inc.	Oxazolidinedione hypoglycemic agents
GB9225386D0 (en) *	1992-12-04	1993-01-27	Smithkline Beecham Plc	Novel compounds
TW268952B (ko)	1993-02-26	1996-01-21	Takeda Pharm Industry Co Ltd
US5591862A (en)	1993-06-11	1997-01-07	Takeda Chemical Industries, Ltd.	Tetrazole derivatives, their production and use
JP3466273B2 (ja) *	1993-06-11	2003-11-10	武田薬品工業株式会社	テトラゾール誘導体、その製造法およびそれを含んでなる医薬
ATE179709T1 (de) *	1993-12-27	1999-05-15	Japan Tobacco Inc	Isoxazolidindionderivate und deren verwendung
JPH08325263A (ja) *	1995-05-31	1996-12-10	Sumitomo Metal Ind Ltd	新規２−アミノ−３−フェニルプロピオン酸誘導体
GB9604242D0 (en) *	1996-02-28	1996-05-01	Glaxo Wellcome Inc	Chemical compounds
EP0925063A4 (en) *	1996-07-01	2000-12-27	Lilly Co Eli	Blood-glucose-lowering and lipid-lowering compounds

1997
- 1997-08-19 CZ CZ99536A patent/CZ53699A3/cs unknown
- 1997-08-19 RU RU99105567/04A patent/RU2174121C2/ru not_active IP Right Cessation
- 1997-08-19 EP EP97935823A patent/EP0930299A1/en not_active Withdrawn
- 1997-08-19 CN CN97198837A patent/CN1233241A/zh active Pending
- 1997-08-19 WO PCT/JP1997/002873 patent/WO1998007699A1/ja not_active Application Discontinuation
- 1997-08-19 IL IL12860097A patent/IL128600A0/xx unknown
- 1997-08-19 EE EEP199900069A patent/EE03765B1/xx not_active IP Right Cessation
- 1997-08-19 BR BR9711627A patent/BR9711627A/pt unknown
- 1997-08-19 AU AU38665/97A patent/AU740444B2/en not_active Ceased
- 1997-08-19 PL PL97331861A patent/PL331861A1/xx unknown
- 1997-08-19 SK SK210-99A patent/SK21099A3/sk unknown
- 1997-08-19 KR KR1019997001230A patent/KR20000068151A/ko not_active Application Discontinuation
- 1997-08-19 NZ NZ334738A patent/NZ334738A/xx unknown
- 1997-08-19 US US09/242,620 patent/US6204277B1/en not_active Expired - Fee Related
- 1997-08-19 CA CA002263721A patent/CA2263721A1/en not_active Abandoned
1999
- 1999-02-15 NO NO19990700A patent/NO312160B1/no unknown
- 1999-03-18 BG BG103268A patent/BG103268A/xx unknown

Also Published As

Publication number	Publication date
NO990700D0 (no)	1999-02-15
KR20000068151A (ko)	2000-11-25
US6204277B1 (en)	2001-03-20
WO1998007699A1 (fr)	1998-02-26
EE03765B1 (et)	2002-06-17
CN1233241A (zh)	1999-10-27
BG103268A (en)	2000-12-29
NO990700L (no)	1999-04-19
CA2263721A1 (en)	1998-02-26
NZ334738A (en)	2001-01-26
PL331861A1 (en)	1999-08-16
EP0930299A1 (en)	1999-07-21
AU740444B2 (en)	2001-11-01
CZ53699A3 (cs)	1999-07-14
RU2174121C2 (ru)	2001-09-27
AU3866597A (en)	1998-03-06
EE9900069A (et)	1999-10-15
BR9711627A (pt)	1999-08-24
EP0930299A4 (ko)	1999-07-21
IL128600A0 (en)	2000-01-31
SK21099A3 (en)	2000-05-16

Publication	Publication Date	Title
NO312160B1 (no)	2002-04-02	Propionsyrederivater og farmasöytiske sammensetninger inneholdende disse
JP3997491B2 (ja)	2007-10-24	カルバゾール誘導体、その溶媒和物、又は薬学的に許容されるその塩
EP2216330A1 (en)	2010-08-11	Oxadiazolidinedione compound
EP0684242B1 (en)	1999-05-06	Isoxazolidinedione derivative and use thereof
EP2077846B1 (en)	2011-10-12	Benzoxazepine compounds, their preparation and use
HUT70153A (en)	1995-09-28	Hypoglycemic hydroxyurea derivatives
NO316515B1 (no)	2004-02-02	Nye tricykliske forbindelser og deres anvendelse i medisin, fremgangsmåte for deres fremstillling og farmasøytiske sammensetninger inneholdende dem
WO1997046556A1 (en)	1997-12-11	OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY
JP2011016722A (ja)	2011-01-27	チアゾリジンジオン化合物
EP1562920B1 (en)	2006-06-28	Antiinflammatory 3-arylthio-3-thiazolyl-alkylamines
EA019091B1 (ru)	2014-01-30	Агонист глюкокортикоидного рецептора, включающий 2,2,4-триметил-6-фенил-1,2-дигидрохинолиновые производные, содержащие замещенную оксигруппу
FI91870C (fi)	1994-08-25	Menetelmä antidiabeettisina aineina käytettävien bentsoksatsiinijohdannaisten valmistamiseksi
CA2163950A1 (en)	1996-05-30	2-substituted benzothiazole derivatives and prophylactic and therapeutic agents for the treatment of diabetic complications
RU2536409C2 (ru)	2014-12-20	Амидное производное
JP3215048B2 (ja)	2001-10-02	プロピオン酸誘導体及びその用途
CN102558167A (zh)	2012-07-11	Gk和ppar双重激动活性的噻唑烷二酮衍生物
CN111393421B (zh)	2021-08-31	丁烯酸内酯类衍生物及其制备方法与应用
EP1280784B1 (en)	2007-06-27	Biologically active 4h-benzo 1,4\|oxazin-3-ones
JPH07188227A (ja)	1995-07-25	チアゾリジン誘導体及びオキサゾール誘導体
CN110857268B (zh)	2022-10-04	苯氧酸类化合物及其医药用途
MXPA99001667A (en)	1999-09-01	Propionic acid derivatives and applications thereof
KR20150130177A (ko)	2015-11-23	Sglt 저해제로서 2,3-다이하이드로벤조퓨란 유도체 및 이를 포함하는 약학적 조성물
CN113214222B (zh)	2024-06-21	N-(芳基磺酰基)-吲哚-2-甲酰胺类FBPase抑制剂及其用途
JP3798836B2 (ja)	2006-07-19	２−置換ベンゾチアゾール誘導体およびそれを含有する糖尿病合併症予防・治療剤
JP2018535192A (ja)	2018-11-29	１，４−ジ−（４−メチルチオフェニル）−３−フタロイルアゼチジン−２−オンおよびその誘導体