FI62820C - Foerfarande foer framstaellning av terapeutiskt anvaendbara sustituerade oxokarboxylsyror - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara sustituerade oxokarboxylsyror Download PDFInfo
- Publication number
- FI62820C FI62820C FI812050A FI812050A FI62820C FI 62820 C FI62820 C FI 62820C FI 812050 A FI812050 A FI 812050A FI 812050 A FI812050 A FI 812050A FI 62820 C FI62820 C FI 62820C
- Authority
- FI
- Finland
- Prior art keywords
- acid
- group
- salt
- converted
- hydrogen atom
- Prior art date
Links
- 239000002253 acid Substances 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 150000007513 acids Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 150000005690 diesters Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 229910052801 chlorine Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 241000277284 Salvelinus fontinalis Species 0.000 claims 1
- 230000000911 decarboxylating effect Effects 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 239000001307 helium Substances 0.000 claims 1
- 229910052734 helium Inorganic materials 0.000 claims 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims 1
- 239000006188 syrup Substances 0.000 claims 1
- 235000020357 syrup Nutrition 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 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 14
- 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000008103 glucose Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 230000003914 insulin secretion Effects 0.000 description 11
- 210000000496 pancreas Anatomy 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 6
- 108090001061 Insulin Proteins 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 6
- 229940125396 insulin Drugs 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- UOQNGAWDDLUVMX-UHFFFAOYSA-N 5-(4-chlorophenyl)-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CCCC1=CC=C(Cl)C=C1 UOQNGAWDDLUVMX-UHFFFAOYSA-N 0.000 description 5
- SOGVHCKNCUCLOY-UHFFFAOYSA-N 6-(4-methoxyphenyl)-2-oxohexanoic acid Chemical compound COC1=CC=C(CCCCC(=O)C(O)=O)C=C1 SOGVHCKNCUCLOY-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- -1 aminoalkanols Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003797 solvolysis reaction Methods 0.000 description 4
- KODALSDOOPIEJT-UHFFFAOYSA-N 2-oxo-6-phenylhexanoic acid Chemical compound OC(=O)C(=O)CCCCC1=CC=CC=C1 KODALSDOOPIEJT-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- PHEQVYPLXGUQLA-UHFFFAOYSA-N 5-(4-chlorophenyl)-2-ethoxycarbonylpentanoic acid Chemical compound CCOC(=O)C(C(O)=O)CCCC1=CC=C(Cl)C=C1 PHEQVYPLXGUQLA-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 238000005684 Liebig rearrangement reaction Methods 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
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 108010005991 Pork Regular Insulin Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- YKYOUMDCQGMQQO-UHFFFAOYSA-L cadmium dichloride Chemical compound Cl[Cd]Cl YKYOUMDCQGMQQO-UHFFFAOYSA-L 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- ZATZZEDUXZRCMY-UHFFFAOYSA-N diethyl 2-[3-(4-chlorophenyl)propyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CCCC1=CC=C(Cl)C=C1 ZATZZEDUXZRCMY-UHFFFAOYSA-N 0.000 description 2
- IYJNHJVLQSETTK-UHFFFAOYSA-N diethyl 2-[4-[3-(trifluoromethyl)phenyl]butyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CCCCC1=CC=CC(C(F)(F)F)=C1 IYJNHJVLQSETTK-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- UIGNVQBUMWQRBG-UHFFFAOYSA-N ethyl 8-(2,4-dimethylphenyl)-7-oxooctanoate Chemical compound CCOC(=O)CCCCCC(=O)CC1=CC=C(C)C=C1C UIGNVQBUMWQRBG-UHFFFAOYSA-N 0.000 description 2
- JDZRPXKLASQUFT-UHFFFAOYSA-N ethyl 9-(4-chlorophenyl)-9-oxononanoate Chemical compound CCOC(=O)CCCCCCCC(=O)C1=CC=C(Cl)C=C1 JDZRPXKLASQUFT-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000002473 insulinotropic effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000004715 keto acids Chemical class 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
- WMFHUUKYIUOHRA-UHFFFAOYSA-N (3-phenoxyphenyl)methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC(OC=2C=CC=CC=2)=C1 WMFHUUKYIUOHRA-UHFFFAOYSA-N 0.000 description 1
- AZLYAPKPZBXCGX-UHFFFAOYSA-N 1-(2-bromoethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCBr)=C1 AZLYAPKPZBXCGX-UHFFFAOYSA-N 0.000 description 1
- WGLUZJWOTTXZIC-UHFFFAOYSA-N 1-(bromomethyl)-2,4-dimethylbenzene Chemical compound CC1=CC=C(CBr)C(C)=C1 WGLUZJWOTTXZIC-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- ZIRLDYOJRFPDFO-UHFFFAOYSA-N 1-butyl-1-(4-methylphenyl)sulfonylurea Chemical compound CCCCN(C(N)=O)S(=O)(=O)C1=CC=C(C)C=C1 ZIRLDYOJRFPDFO-UHFFFAOYSA-N 0.000 description 1
- QMOIRPUDEIVBER-UHFFFAOYSA-N 10-(4-methylphenyl)-2-oxodecanoic acid Chemical compound CC1=CC=C(CCCCCCCCC(=O)C(O)=O)C=C1 QMOIRPUDEIVBER-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
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 description 1
- JTYSMJJLVLQPQV-UHFFFAOYSA-N 2-oxo-7-[3-(trifluoromethyl)phenyl]heptanoic acid Chemical compound OC(=O)C(=O)CCCCCC1=CC=CC(C(F)(F)F)=C1 JTYSMJJLVLQPQV-UHFFFAOYSA-N 0.000 description 1
- VNRQPSSLQKAJEZ-UHFFFAOYSA-N 2-oxo-8-[3-(trifluoromethyl)phenyl]octanoic acid Chemical compound OC(=O)C(=O)CCCCCCC1=CC=CC(C(F)(F)F)=C1 VNRQPSSLQKAJEZ-UHFFFAOYSA-N 0.000 description 1
- MRHALFVCSNVTDX-UHFFFAOYSA-N 2-oxo-9-[3-(trifluoromethyl)phenyl]nonanoic acid Chemical compound OC(=O)C(=O)CCCCCCCC1=CC=CC(C(F)(F)F)=C1 MRHALFVCSNVTDX-UHFFFAOYSA-N 0.000 description 1
- ZHBIWFGGIKFSHZ-UHFFFAOYSA-N 3-(4-chlorophenyl)propan-1-ol Chemical compound OCCCC1=CC=C(Cl)C=C1 ZHBIWFGGIKFSHZ-UHFFFAOYSA-N 0.000 description 1
- UGPJZJOLEFSARU-UHFFFAOYSA-N 3-(4-chlorophenyl)propyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCCC1=CC=C(Cl)C=C1 UGPJZJOLEFSARU-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
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- GEKATFHSQNGKLM-UHFFFAOYSA-N 5-(4-methoxyphenyl)-2-oxopentanoic acid Chemical compound COC1=CC=C(CCCC(=O)C(O)=O)C=C1 GEKATFHSQNGKLM-UHFFFAOYSA-N 0.000 description 1
- VPAPSEYKVPULKR-UHFFFAOYSA-N 6-[3-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid Chemical group N1=CC(C(=O)O)=CC=C1C1=CC=CC(C(F)(F)F)=C1 VPAPSEYKVPULKR-UHFFFAOYSA-N 0.000 description 1
- VBQVTCHWYHXVCQ-UHFFFAOYSA-N 7-(3-chlorophenyl)-2-oxoheptanoic acid Chemical compound OC(=O)C(=O)CCCCCC1=CC=CC(Cl)=C1 VBQVTCHWYHXVCQ-UHFFFAOYSA-N 0.000 description 1
- WMTRACVXDLVFAV-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-oxoheptanoic acid Chemical compound COC1=CC=C(CCCCCC(=O)C(O)=O)C=C1 WMTRACVXDLVFAV-UHFFFAOYSA-N 0.000 description 1
- ZXPRLKLGLOZXRJ-UHFFFAOYSA-N 7-(4-methylphenyl)-2-oxoheptanoic acid Chemical compound CC1=CC=C(CCCCCC(=O)C(O)=O)C=C1 ZXPRLKLGLOZXRJ-UHFFFAOYSA-N 0.000 description 1
- XKROLWOYNAMKSY-UHFFFAOYSA-N 8-(3-fluorophenyl)-2-oxooctanoic acid Chemical compound OC(=O)C(=O)CCCCCCC1=CC=CC(F)=C1 XKROLWOYNAMKSY-UHFFFAOYSA-N 0.000 description 1
- CXPPKHLOIATDPL-UHFFFAOYSA-N 8-(4-butoxyphenyl)-2-oxooctanoic acid Chemical compound CCCCOC1=CC=C(CCCCCCC(=O)C(O)=O)C=C1 CXPPKHLOIATDPL-UHFFFAOYSA-N 0.000 description 1
- ZUVHKFNDZOYXTH-UHFFFAOYSA-N 8-(4-hydroxyphenyl)-2-oxooctanoic acid Chemical compound OC(=O)C(=O)CCCCCCC1=CC=C(O)C=C1 ZUVHKFNDZOYXTH-UHFFFAOYSA-N 0.000 description 1
- CBYKAPWPXLHCPQ-UHFFFAOYSA-N 9-(2,4-dimethylphenyl)-2-oxononanoic acid Chemical compound CC1=CC=C(CCCCCCCC(=O)C(O)=O)C(C)=C1 CBYKAPWPXLHCPQ-UHFFFAOYSA-N 0.000 description 1
- SXMBOXQAMIMSQL-UHFFFAOYSA-N 9-(4-chlorophenyl)-2-oxononanoic acid Chemical compound OC(=O)C(=O)CCCCCCCC1=CC=C(Cl)C=C1 SXMBOXQAMIMSQL-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GAVRTJRQLCPSMD-UHFFFAOYSA-N Cl.CCOC(=O)CCCCCCCC(O)=O Chemical compound Cl.CCOC(=O)CCCCCCCC(O)=O GAVRTJRQLCPSMD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 239000012839 Krebs-Henseleit buffer Substances 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 241001442654 Percnon planissimum Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- WWONVNOPBYOTAK-UHFFFAOYSA-N diethyl 2-[6-(2,4-dimethylphenyl)hexyl]-3-oxobutanedioate Chemical compound CCOC(=O)C(=O)C(C(=O)OCC)CCCCCCC1=CC=C(C)C=C1C WWONVNOPBYOTAK-UHFFFAOYSA-N 0.000 description 1
- QZJPSRUCLIAYHL-UHFFFAOYSA-N diethyl 2-[7-(2,4-dimethylphenyl)heptyl]-3-oxobutanedioate Chemical compound CCOC(=O)C(=O)C(C(=O)OCC)CCCCCCCC1=CC=C(C)C=C1C QZJPSRUCLIAYHL-UHFFFAOYSA-N 0.000 description 1
- PRPUZVMZHOCTCH-UHFFFAOYSA-N diethyl 2-oxo-3-(3-phenylpropyl)butanedioate Chemical compound CCOC(=O)C(=O)C(C(=O)OCC)CCCC1=CC=CC=C1 PRPUZVMZHOCTCH-UHFFFAOYSA-N 0.000 description 1
- SEAROHGCQMXOAE-UHFFFAOYSA-N diethyl 2-oxo-3-[4-[3-(trifluoromethyl)phenyl]butyl]butanedioate Chemical compound CCOC(=O)C(=O)C(C(=O)OCC)CCCCC1=CC=CC(C(F)(F)F)=C1 SEAROHGCQMXOAE-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000000667 effect on insulin Effects 0.000 description 1
- YFVAOLUTXVNELE-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)-2-methylpentanoate Chemical compound CCOC(=O)C(C)CCCC1=CC=C(Cl)C=C1 YFVAOLUTXVNELE-UHFFFAOYSA-N 0.000 description 1
- OFXZGJOUTXCFTA-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)-2-oxopentanoate Chemical compound CCOC(=O)C(=O)CCCC1=CC=C(Cl)C=C1 OFXZGJOUTXCFTA-UHFFFAOYSA-N 0.000 description 1
- WNWZAZCARBDNOG-UHFFFAOYSA-N ethyl 5-(4-methoxyphenyl)pentanoate Chemical compound CCOC(=O)CCCCC1=CC=C(OC)C=C1 WNWZAZCARBDNOG-UHFFFAOYSA-N 0.000 description 1
- QCHDRUGIAZBPGB-UHFFFAOYSA-N ethyl 5-phenylpentanoate Chemical compound CCOC(=O)CCCCC1=CC=CC=C1 QCHDRUGIAZBPGB-UHFFFAOYSA-N 0.000 description 1
- RKRCDHOZTUHOPF-UHFFFAOYSA-N ethyl 6-[3-(trifluoromethyl)phenyl]hexanoate Chemical compound CCOC(=O)CCCCCC1=CC=CC(C(F)(F)F)=C1 RKRCDHOZTUHOPF-UHFFFAOYSA-N 0.000 description 1
- QHLKPOFWNHSOAN-UHFFFAOYSA-N ethyl 8-(2,4-dimethylphenyl)octanoate Chemical compound CCOC(=O)CCCCCCCC1=CC=C(C)C=C1C QHLKPOFWNHSOAN-UHFFFAOYSA-N 0.000 description 1
- ZPXNWIWSIRXTEQ-UHFFFAOYSA-N ethyl 9-(4-chlorophenyl)nonanoate Chemical compound CCOC(=O)CCCCCCCCC1=CC=C(Cl)C=C1 ZPXNWIWSIRXTEQ-UHFFFAOYSA-N 0.000 description 1
- 230000001610 euglycemic effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 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
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical class COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002886 octanoic acid esters Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 210000005166 vasculature Anatomy 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/08—Cadmium compounds
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/84—Unsaturated compounds containing keto groups containing six membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/88—Unsaturated compounds containing keto groups containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH978579 | 1979-10-31 | ||
| CH978579 | 1979-10-31 | ||
| PCT/EP1980/000123 WO1981001285A1 (en) | 1979-10-31 | 1980-10-31 | Substituted carboxylic ceto-acids,process for the preparation thereof,use thereof and medicinal compositions containing them |
| EP8000123 | 1980-10-31 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI812050L FI812050L (fi) | 1981-06-30 |
| FI62820B FI62820B (fi) | 1982-11-30 |
| FI62820C true FI62820C (fi) | 1983-03-10 |
Family
ID=4355617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI812050A FI62820C (fi) | 1979-10-31 | 1981-06-30 | Foerfarande foer framstaellning av terapeutiskt anvaendbara sustituerade oxokarboxylsyror |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4334089A (ja) |
| EP (2) | EP0051077A1 (ja) |
| JP (1) | JPH0231705B2 (ja) |
| AU (1) | AU542902B2 (ja) |
| CA (1) | CA1176273A (ja) |
| DE (2) | DE3041097A1 (ja) |
| DK (1) | DK158460C (ja) |
| ES (1) | ES496382A0 (ja) |
| FI (1) | FI62820C (ja) |
| GR (1) | GR70727B (ja) |
| HU (1) | HU187337B (ja) |
| IE (1) | IE50471B1 (ja) |
| IL (1) | IL61371A (ja) |
| NZ (1) | NZ195415A (ja) |
| PT (1) | PT71998B (ja) |
| WO (1) | WO1981001285A1 (ja) |
| ZA (1) | ZA806681B (ja) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2481118A1 (fr) * | 1980-04-24 | 1981-10-30 | Roussel Uclaf | Application a titre de medicaments de derives substitues de l'acide phenyl-4-oxo-2-butenoique |
| EP0134216A4 (en) * | 1983-01-13 | 1985-07-01 | Ethyl Corp | METHOD FOR PRODUCING ALPHA KETO CARBONIC ACIDS. |
| FR2549469B1 (fr) * | 1983-07-18 | 1985-11-08 | Hoechst France | Procede de preparation du phenylpyruvate de sodium monohydrate cristallise |
| JP2533651B2 (ja) * | 1988-09-13 | 1996-09-11 | 財団法人相模中央化学研究所 | ２―オキソ―３―芳香族カルボン酸誘導体の製造方法 |
| US4912255A (en) * | 1989-04-13 | 1990-03-27 | Chan Albert S | Process for preparing sodium phenylpyruvate from calcium phenylpyruvate |
| JPH0454806U (ja) * | 1990-09-18 | 1992-05-11 | ||
| JPH05337913A (ja) * | 1992-12-22 | 1993-12-21 | Chichibu Cement Co Ltd | 舗装用ブロック材の成形法及びその加熱装置 |
| IS4164A (is) * | 1993-06-11 | 1994-12-12 | Ab Astra | Efnasambönd sem hindra flæði magasýru |
| US5556863A (en) * | 1993-06-11 | 1996-09-17 | Astra Aktiebolag | Compound for gastric acid secretion inhibition |
| EP1594439A2 (en) * | 2003-02-13 | 2005-11-16 | Albert Einstein College Of Medicine Of Yeshiva University | REGULATION OF FOOD INTAKE AND GLUCOSE PRODUCTION BY MODULATION OF LONG-CHAIN FATTY ACYL-CoA LEVELS IN THE HYPOTHALAMUS |
| WO2006041922A2 (en) * | 2004-10-08 | 2006-04-20 | Dara Biosciences, Inc. | Agents and methods for administration to the central nervous system |
| US20070026079A1 (en) * | 2005-02-14 | 2007-02-01 | Louis Herlands | Intranasal administration of modulators of hypothalamic ATP-sensitive potassium channels |
| US9324015B2 (en) * | 2012-05-22 | 2016-04-26 | Checkpoint Systems, Inc. | Solid housing tag |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3182061A (en) * | 1961-03-20 | 1965-05-04 | Warner Lambert Pharmaceutical | 5-[4-(p-hydroxyphenoxy)phenyl]-5-oxo-3-methylvaleric acid |
| US3592846A (en) * | 1967-11-28 | 1971-07-13 | Sun Oil Co | Hydroxy-phenyl-alpha-ketobutyric acids |
| FR2127265A5 (ja) * | 1971-03-02 | 1972-10-13 | Ugine Kuhlmann | |
| JPS5227147B1 (ja) * | 1971-06-16 | 1977-07-19 | ||
| US4029699A (en) * | 1971-09-13 | 1977-06-14 | Takeda Chemical Industries, Ltd. | 3,(2,4,5-Trisubstituted benzoyl)-propionic acid and the salts thereof |
| DE2365755A1 (de) * | 1972-09-12 | 1976-04-08 | Sagami Chem Res | Alpha-ketosaeurederivate und verfahren zu ihrer herstellung |
| JPS5116634A (en) * | 1974-07-29 | 1976-02-10 | Nisshin Flour Milling Co | Pirubinsanno seizoho |
-
1980
- 1980-10-29 ES ES496382A patent/ES496382A0/es active Granted
- 1980-10-30 ZA ZA00806681A patent/ZA806681B/xx unknown
- 1980-10-30 PT PT71998A patent/PT71998B/pt unknown
- 1980-10-30 NZ NZ195415A patent/NZ195415A/xx unknown
- 1980-10-30 IL IL61371A patent/IL61371A/xx unknown
- 1980-10-30 IE IE2250/80A patent/IE50471B1/en unknown
- 1980-10-30 CA CA000363592A patent/CA1176273A/en not_active Expired
- 1980-10-30 GR GR63239A patent/GR70727B/el unknown
- 1980-10-31 AU AU63986/80A patent/AU542902B2/en not_active Ceased
- 1980-10-31 EP EP80106676A patent/EP0051077A1/de active Pending
- 1980-10-31 WO PCT/EP1980/000123 patent/WO1981001285A1/de active IP Right Grant
- 1980-10-31 HU HU801840A patent/HU187337B/hu not_active IP Right Cessation
- 1980-10-31 DE DE19803041097 patent/DE3041097A1/de not_active Withdrawn
- 1980-10-31 DE DE8080902059T patent/DE3069883D1/de not_active Expired
- 1980-10-31 US US06/279,961 patent/US4334089A/en not_active Expired - Fee Related
- 1980-10-31 JP JP55502477A patent/JPH0231705B2/ja not_active Expired - Lifetime
-
1981
- 1981-05-19 EP EP80902059A patent/EP0038343B1/de not_active Expired
- 1981-06-29 DK DK287881A patent/DK158460C/da not_active IP Right Cessation
- 1981-06-30 FI FI812050A patent/FI62820C/fi not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HU187337B (en) | 1985-12-28 |
| EP0038343A1 (de) | 1981-10-28 |
| FI62820B (fi) | 1982-11-30 |
| GR70727B (ja) | 1983-01-24 |
| ES8202780A1 (es) | 1982-03-01 |
| PT71998A (en) | 1980-11-01 |
| IL61371A0 (en) | 1980-12-31 |
| DE3069883D1 (en) | 1985-02-07 |
| NZ195415A (en) | 1982-09-14 |
| CA1176273A (en) | 1984-10-16 |
| ZA806681B (en) | 1981-10-28 |
| JPS56501523A (ja) | 1981-10-22 |
| IL61371A (en) | 1985-02-28 |
| US4334089A (en) | 1982-06-08 |
| ES496382A0 (es) | 1982-03-01 |
| IE802250L (en) | 1981-04-30 |
| AU542902B2 (en) | 1985-03-21 |
| DK287881A (da) | 1981-06-29 |
| EP0051077A1 (de) | 1982-05-12 |
| EP0038343B1 (de) | 1984-12-27 |
| DK158460B (da) | 1990-05-21 |
| JPH0231705B2 (ja) | 1990-07-16 |
| DE3041097A1 (de) | 1981-05-14 |
| FI812050L (fi) | 1981-06-30 |
| WO1981001285A1 (en) | 1981-05-14 |
| DK158460C (da) | 1990-10-08 |
| PT71998B (en) | 1982-03-31 |
| IE50471B1 (en) | 1986-04-30 |
| AU6398680A (en) | 1981-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI62820C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara sustituerade oxokarboxylsyror | |
| US4886807A (en) | Novel pyrimidopyrimidine derivative, process for producing it and pharmaceutical composition | |
| WO2007032466A1 (ja) | 複素環化合物、その製造方法並びに用途 | |
| CZ20032696A3 (cs) | Thiohydantoiny a jejich použití při léčení cukrovky | |
| US20030120072A1 (en) | Decahydro-isoquinolines | |
| SK135699A3 (en) | Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use | |
| EP0302788A1 (fr) | Dérivés de [(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 9H-pyrido[3,4-b]indole, leur préparation et leur application en thérapeutique | |
| FI110940B (fi) | Menetelmä terapeuttisesti aktiivisten kinoloni- ja akridonijohdannaisten valmistamiseksi | |
| CA1248532A (en) | Pyrazolo¬3,4-b|pyridine derivatives and process for producing them | |
| FR2645152A1 (fr) | 3h-pteridinones-4, procedes de preparation et medicaments les contenant | |
| KR20090106633A (ko) | ＰＤＥ5 억제제로서 유용한 6-벤질-2,3,4,7-테트라히드로-인돌로[2,3-ｃ]퀴놀린 화합물 | |
| US5202324A (en) | Imidazopyridazines | |
| US5250547A (en) | Benzopyran derivatives | |
| EP0223744B1 (en) | Flavone derivatives | |
| US5155108A (en) | Imidazopyridazines and use as antiasthmatic agents | |
| KR880001988B1 (ko) | 헤테로사이클릭 화합물의 제조방법 | |
| RU2081872C1 (ru) | Производные дигидропиридина, смесь их изомеров, индивидуальные изомеры или их физиологически переносимые соли, способы их получения, промежуточные соединения и способ их получения | |
| JPS6210087A (ja) | ４，７−ジヒドロチエノ〔２，３−ｂ〕ピリジン誘導体，その製造法および循環器系疾患治療剤 | |
| EP0021857A1 (fr) | Dérivés de l'indole, leur préparation et medicaments les contenant | |
| JPS5982385A (ja) | Ｎ−置換−２−（１−イミダゾリル）インド−ル、その製法および該化合物を含有する医薬製剤 | |
| EP0153230B1 (fr) | Nouveaux dérivés du pyrimido /2,1-b/ benzothiazole et leurs sels, procédé et intermédiaires de préparation, application à titre de médicaments et compositions les renfermant | |
| US4631283A (en) | Ortho substituted dihydroxy-2(1H)quinazolinone-1-alkanoic acids | |
| EP0302787B1 (fr) | Dérivés de (pipéridinyl-4)méthyl-2 benzofuro[2,3-c]pyridines, leur préparation et leur application en thérapeutique | |
| JP2753146B2 (ja) | ビス−アザー二環式抗不安薬の製法および中間体 | |
| PT87927B (pt) | Processo para a preparacao de acidos 3,5-dihidroxi-hepta-6-enoicos substituidos por 7-(1h-pirrol-3-ilo), das suas correspondentes delta-lactonas e sais, e de composicoes farmaceuticas que os contem |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: BYK GULDEN LOMBERG CHEMISCHE FABRIK |