SK472000A3 - Polyhydroxyalkylpyrazine derivatives, preparation and medicines containing them - Google Patents

Polyhydroxyalkylpyrazine derivatives, preparation and medicines containing them Download PDF

Info

Publication number: SK472000A3
Authority: SK; Slovakia
Prior art keywords: tetraol; pyrazin; butane; trihydroxybutyl; formula
Prior art date: 1997-07-17

Application number

SK47-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Georges Bashiardes

Jean-Christophe Carry

Michel Evers

Bruno Filoche

Serge Mignani

Original Assignee

Rhone Poulenc Rorer Sa

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.)

1997-07-17

Filing date

1998-07-15

Publication date

2000-06-12

1998-07-15 Application filed by Rhone Poulenc Rorer Sa filed Critical Rhone Poulenc Rorer Sa

2000-06-12 Publication of SK472000A3 publication Critical patent/SK472000A3/sk

Links

239000003814 drug Substances 0.000 title claims abstract description 13
238000002360 preparation method Methods 0.000 title claims abstract description 13
229940079593 drug Drugs 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 57
150000003839 salts Chemical class 0.000 claims abstract description 27
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 79
238000000034 method Methods 0.000 claims description 29
239000000203 mixture Substances 0.000 claims description 27
150000007522 mineralic acids Chemical class 0.000 claims description 19
150000007524 organic acids Chemical class 0.000 claims description 18
239000004480 active ingredient Substances 0.000 claims description 13
206010012601 diabetes mellitus Diseases 0.000 claims description 12
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 11
150000001323 aldoses Chemical class 0.000 claims description 10
-1 organic acid salt Chemical class 0.000 claims description 10
239000001913 cellulose Substances 0.000 claims description 7
229920002678 cellulose Polymers 0.000 claims description 7
WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims description 6
208000007976 Ketosis Diseases 0.000 claims description 6
150000002584 ketoses Chemical class 0.000 claims description 6
NPWQIVOYGNUVEB-JKCCIXDMSA-N (1r,2r,3r)-1-[5-[(1r,2r,3r)-1,2,3,4-tetrahydroxybutyl]pyrazin-2-yl]butane-1,2,3,4-tetrol Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)C1=CN=C([C@@H](O)[C@@H](O)[C@H](O)CO)C=N1 NPWQIVOYGNUVEB-JKCCIXDMSA-N 0.000 claims description 5
FBDICDJCXVZLIP-VSSNEEPJSA-N (1r,2s,3r)-1-[5-[(2s,3r)-2,3,4-trihydroxybutyl]pyrazin-2-yl]butane-1,2,3,4-tetrol Chemical compound OC[C@@H](O)[C@@H](O)CC1=CN=C([C@@H](O)[C@H](O)[C@H](O)CO)C=N1 FBDICDJCXVZLIP-VSSNEEPJSA-N 0.000 claims description 5
MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 4
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
BJHIKXHVCXFQLS-PUFIMZNGSA-N D-psicose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C(=O)CO BJHIKXHVCXFQLS-PUFIMZNGSA-N 0.000 claims description 3
LKDRXBCSQODPBY-IANNHFEVSA-N D-sorbose Chemical compound OCC1(O)OC[C@@H](O)[C@H](O)[C@H]1O LKDRXBCSQODPBY-IANNHFEVSA-N 0.000 claims description 3
LKDRXBCSQODPBY-OEXCPVAWSA-N D-tagatose Chemical compound OCC1(O)OC[C@@H](O)[C@H](O)[C@@H]1O LKDRXBCSQODPBY-OEXCPVAWSA-N 0.000 claims description 3
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 claims description 3
WQZGKKKJIJFFOK-ZZWDRFIYSA-N L-glucose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-ZZWDRFIYSA-N 0.000 claims description 3
WQZGKKKJIJFFOK-RSVSWTKNSA-N D-altro-hexose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-RSVSWTKNSA-N 0.000 claims description 2
LKDRXBCSQODPBY-NSHGFSBMSA-N L-fructose Chemical compound OCC1(O)OC[C@H](O)[C@H](O)[C@H]1O LKDRXBCSQODPBY-NSHGFSBMSA-N 0.000 claims description 2
WQZGKKKJIJFFOK-DHVFOXMCSA-N L-galactose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-DHVFOXMCSA-N 0.000 claims description 2
WQZGKKKJIJFFOK-ZNVMLXAYSA-N L-idopyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-ZNVMLXAYSA-N 0.000 claims description 2
WQZGKKKJIJFFOK-JFNONXLTSA-N L-mannopyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-JFNONXLTSA-N 0.000 claims description 2
BJHIKXHVCXFQLS-ZXEDONINSA-N L-psicose Chemical compound OC[C@H](O)[C@H](O)[C@H](O)C(=O)CO BJHIKXHVCXFQLS-ZXEDONINSA-N 0.000 claims description 2
230000002378 acidificating effect Effects 0.000 claims description 2
GZCGUPFRVQAUEE-ZXXMMSQZSA-N aldehydo-D-idose Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-ZXXMMSQZSA-N 0.000 claims description 2
GZCGUPFRVQAUEE-KAZBKCHUSA-N aldehydo-D-talose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-KAZBKCHUSA-N 0.000 claims description 2
GZCGUPFRVQAUEE-AZGQCCRYSA-N aldehydo-L-altrose Chemical compound OC[C@H](O)[C@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-AZGQCCRYSA-N 0.000 claims description 2
GZCGUPFRVQAUEE-OMMKOOBNSA-N aldehydo-L-talose Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-OMMKOOBNSA-N 0.000 claims description 2
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 2
BJHIKXHVCXFQLS-LFRDXLMFSA-N keto-L-tagatose Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)C(=O)CO BJHIKXHVCXFQLS-LFRDXLMFSA-N 0.000 claims description 2
WQZGKKKJIJFFOK-QRXFDPRISA-N L-gulose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QRXFDPRISA-N 0.000 claims 1
150000002484 inorganic compounds Chemical class 0.000 claims 1
229910010272 inorganic material Inorganic materials 0.000 claims 1
150000002894 organic compounds Chemical class 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 88
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000243 solution Substances 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
235000011114 ammonium hydroxide Nutrition 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
239000000706 filtrate Substances 0.000 description 10
238000010898 silica gel chromatography Methods 0.000 description 10
238000009835 boiling Methods 0.000 description 9
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 8
230000006978 adaptation Effects 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
239000008103 glucose Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
239000002552 dosage form Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
230000002218 hypoglycaemic effect Effects 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 4
150000001720 carbohydrates Chemical class 0.000 description 4
235000014633 carbohydrates Nutrition 0.000 description 4
238000001035 drying Methods 0.000 description 4
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 4
239000002609 medium Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
WGCNASOHLSPBMP-UHFFFAOYSA-N Glycolaldehyde Chemical compound OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
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 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000013078 crystal Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
238000010606 normalization Methods 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
230000002792 vascular Effects 0.000 description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
MBHUNOHYVYVNIP-UHFFFAOYSA-N 1-[6-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol Natural products OCC(O)C(O)CC1=CN=CC(C(O)C(O)C(O)CO)=N1 MBHUNOHYVYVNIP-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
206010003210 Arteriosclerosis Diseases 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
206010017711 Gangrene Diseases 0.000 description 2
102000015779 HDL Lipoproteins Human genes 0.000 description 2
108010010234 HDL Lipoproteins Proteins 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
102000004877 Insulin Human genes 0.000 description 2
108090001061 Insulin Proteins 0.000 description 2
102000007330 LDL Lipoproteins Human genes 0.000 description 2
108010007622 LDL Lipoproteins Proteins 0.000 description 2
208000001344 Macular Edema Diseases 0.000 description 2
206010025415 Macular oedema Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
208000008589 Obesity Diseases 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000008119 colloidal silica Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
201000005577 familial hyperlipidemia Diseases 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
230000002641 glycemic effect Effects 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
230000003345 hyperglycaemic effect Effects 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
229940125396 insulin Drugs 0.000 description 2
201000010230 macular retinal edema Diseases 0.000 description 2
235000020824 obesity Nutrition 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
230000001954 sterilising effect Effects 0.000 description 2
238000004659 sterilization and disinfection Methods 0.000 description 2
239000013589 supplement Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
PMRUCYZFAFUSAY-UHFFFAOYSA-N 1,3-dihydroxypropan-2-one;phosphoric acid Chemical compound OP(O)(O)=O.OCC(=O)CO PMRUCYZFAFUSAY-UHFFFAOYSA-N 0.000 description 1
KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 1
HHDDCCUIIUWNGJ-UHFFFAOYSA-N 3-hydroxypyruvic acid Chemical compound OCC(=O)C(O)=O HHDDCCUIIUWNGJ-UHFFFAOYSA-N 0.000 description 1
IRIUWJQQUVBRLV-UHFFFAOYSA-N 4-fluoro-1,2-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1[N+]([O-])=O IRIUWJQQUVBRLV-UHFFFAOYSA-N 0.000 description 1
JKTORXLUQLQJCM-UHFFFAOYSA-N 4-phosphonobutylphosphonic acid Chemical compound OP(O)(=O)CCCCP(O)(O)=O JKTORXLUQLQJCM-UHFFFAOYSA-N 0.000 description 1
XZXLYGAUEAPJET-UHFFFAOYSA-N 5-amino-3h-1-benzofuran-2-one Chemical compound NC1=CC=C2OC(=O)CC2=C1 XZXLYGAUEAPJET-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
206010002329 Aneurysm Diseases 0.000 description 1
102000006410 Apoproteins Human genes 0.000 description 1
108010083590 Apoproteins Proteins 0.000 description 1
200000000007 Arterial disease Diseases 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
206010061666 Autonomic neuropathy Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
208000031229 Cardiomyopathies Diseases 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
208000002249 Diabetes Complications Diseases 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
206010012655 Diabetic complications Diseases 0.000 description 1
208000008960 Diabetic foot Diseases 0.000 description 1
206010012689 Diabetic retinopathy Diseases 0.000 description 1
GNGACRATGGDKBX-UHFFFAOYSA-N Dihydroxyacetone phosphate Natural products OCC(=O)COP(O)(O)=O GNGACRATGGDKBX-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
208000010228 Erectile Dysfunction Diseases 0.000 description 1
208000003790 Foot Ulcer Diseases 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
208000035150 Hypercholesterolemia Diseases 0.000 description 1
208000035154 Hyperesthesia Diseases 0.000 description 1
206010022491 Insulin resistant diabetes Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
206010024119 Left ventricular failure Diseases 0.000 description 1
208000005230 Leg Ulcer Diseases 0.000 description 1
208000017170 Lipid metabolism disease Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
208000009857 Microaneurysm Diseases 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
206010036105 Polyneuropathy Diseases 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010038848 Retinal detachment Diseases 0.000 description 1
206010038910 Retinitis Diseases 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
102000014701 Transketolase Human genes 0.000 description 1
108010043652 Transketolase Proteins 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
208000034698 Vitreous haemorrhage Diseases 0.000 description 1
VYEYJCBEXFTGBN-UHFFFAOYSA-N acetic acid;1,3-dimethyl-7h-purine-2,6-dione Chemical compound CC(O)=O.O=C1N(C)C(=O)N(C)C2=C1NC=N2 VYEYJCBEXFTGBN-UHFFFAOYSA-N 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004808 allyl alcohols Chemical class 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
QZPSXPBJTPJTSZ-UHFFFAOYSA-N aqua regia Chemical compound Cl.O[N+]([O-])=O QZPSXPBJTPJTSZ-UHFFFAOYSA-N 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
208000037849 arterial hypertension Diseases 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
238000003556 assay Methods 0.000 description 1
WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
229910001626 barium chloride Inorganic materials 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical group C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-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
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
230000004856 capillary permeability Effects 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
CDHICTNQMQYRSM-UHFFFAOYSA-N di(propan-2-yl)alumane Chemical compound CC(C)[AlH]C(C)C CDHICTNQMQYRSM-UHFFFAOYSA-N 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
YSAVZVORKRDODB-WDSKDSINSA-N diethyl tartrate Chemical compound CCOC(=O)[C@@H](O)[C@H](O)C(=O)OCC YSAVZVORKRDODB-WDSKDSINSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
210000000416 exudates and transudate Anatomy 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
150000002337 glycosamines Chemical class 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 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
AVXURJPOCDRRFD-UHFFFAOYSA-N hydroxylamine group Chemical group NO AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
JLPAWRLRMTZCSF-UHFFFAOYSA-N hydroxypyruvaldehyde Chemical compound OCC(=O)C=O JLPAWRLRMTZCSF-UHFFFAOYSA-N 0.000 description 1
208000006575 hypertriglyceridemia Diseases 0.000 description 1
125000000879 imine group Chemical group 0.000 description 1
201000001881 impotence Diseases 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
201000005518 mononeuropathy Diseases 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
201000000585 muscular atrophy Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
208000035824 paresthesia Diseases 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
238000000053 physical method Methods 0.000 description 1
239000006187 pill Substances 0.000 description 1
230000007824 polyneuropathy Effects 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
150000003142 primary aromatic amines Chemical class 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000000197 pyrolysis Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000004264 retinal detachment Effects 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
238000004904 shortening Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
KEAYESYHFKHZAL-BJUDXGSMSA-N sodium-22 Chemical compound [22Na] KEAYESYHFKHZAL-BJUDXGSMSA-N 0.000 description 1
HKQLYXRSURHCPY-UHFFFAOYSA-M sodium;ethanol;benzoate Chemical compound [Na+].CCO.[O-]C(=O)C1=CC=CC=C1 HKQLYXRSURHCPY-UHFFFAOYSA-M 0.000 description 1
XXEGCVDKHPRBPJ-UHFFFAOYSA-M sodium;propane-1,2-diol;hydroxide Chemical compound [OH-].[Na+].CC(O)CO XXEGCVDKHPRBPJ-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000002627 tracheal intubation Methods 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Diabetes (AREA)
Epidemiology (AREA)
Hematology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Obesity (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Medicinal Preparation (AREA)

SK47-2000A 1997-07-17 1998-07-15 Polyhydroxyalkylpyrazine derivatives, preparation and medicines containing them SK472000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9709060A FR2766184B1 (fr)	1997-07-17	1997-07-17	Medicaments contenant en tant que principe actif au moins un derive de polyhydroxylalkylpyrazine, les nouveaux derives de polyhydroxylalkylpyrazine et leur preparation
PCT/FR1998/001544 WO1999003842A1 (fr)	1997-07-17	1998-07-15	Derives de polyhydroxylalkylpyrazine, leur preparation, medicaments les contenant

Publications (1)

Publication Number	Publication Date
SK472000A3 true SK472000A3 (en)	2000-06-12

Family

ID=9509303

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK47-2000A SK472000A3 (en)	1997-07-17	1998-07-15	Polyhydroxyalkylpyrazine derivatives, preparation and medicines containing them

Country Status (24)

Country	Link
US (2)	US6392042B1 (de)
EP (1)	EP0998465B1 (de)
JP (1)	JP4443034B2 (de)
KR (1)	KR20010021822A (de)
CN (1)	CN1264370A (de)
AT (1)	ATE249442T1 (de)
AU (1)	AU751090B2 (de)
BR (1)	BR9811013A (de)
CA (1)	CA2296739C (de)
CZ (1)	CZ290908B6 (de)
DE (1)	DE69818060T2 (de)
DK (1)	DK0998465T3 (de)
ES (1)	ES2206978T3 (de)
FR (1)	FR2766184B1 (de)
HU (1)	HUP0002821A3 (de)
IL (1)	IL134038A0 (de)
MX (1)	MXPA00000252A (de)
NO (1)	NO20000055L (de)
NZ (1)	NZ502276A (de)
PL (1)	PL338133A1 (de)
RU (1)	RU2192420C2 (de)
SK (1)	SK472000A3 (de)
WO (1)	WO1999003842A1 (de)
ZA (1)	ZA986334B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1704862A1 (de) *	2005-03-24	2006-09-27	Rottapharm S.p.A.	2,5-bis(tetrahydroxybutyl)pyrazin-Derivaten zur Behandlung von Osteoarthritis und rheumatoider Arthritis
CN100371330C (zh) *	2006-01-24	2008-02-27	湖南中烟工业公司	从糖氨反应液中分离提纯多羟基烷基吡嗪类化合物的方法
CN105294579B (zh) *	2015-11-27	2018-07-20	中国科学院山西煤炭化学研究所	一种利用甲壳素类生物质制备脱氧果糖嗪的方法
US11091446B2 (en) *	2017-03-24	2021-08-17	R.J. Reynolds Tobacco Company	Methods of selectively forming substituted pyrazines

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL64267A (en) *	1980-12-09	1985-08-30	Erba Farmitalia	Ethers of hydroxymethylpyrazin-n-oxides,their preparation and pharmaceutical compositions containing them
WO1995030660A1 (fr) *	1994-05-10	1995-11-16	Firmenich S.A.	Procede pour la preparation de pyrazines substituees
DE19547543A1 (de)	1995-12-20	1997-06-26	Teves Gmbh Alfred	Teilbelagscheibenbremse mit einem Schwimmsattel
FR2744365B1 (fr) *	1996-02-06	1998-02-27	Inst Malgache Rech Appl	Melanges isolables a partir de graines d'eugenia jambolana lamarck, leur preparation et l'utilisation de ces melanges et certains de leurs constituants comme medicaments

1997
- 1997-07-17 FR FR9709060A patent/FR2766184B1/fr not_active Expired - Fee Related
1998
- 1998-07-15 AT AT98939678T patent/ATE249442T1/de not_active IP Right Cessation
- 1998-07-15 CN CN98807301A patent/CN1264370A/zh active Pending
- 1998-07-15 PL PL98338133A patent/PL338133A1/xx not_active Application Discontinuation
- 1998-07-15 WO PCT/FR1998/001544 patent/WO1999003842A1/fr not_active Ceased
- 1998-07-15 SK SK47-2000A patent/SK472000A3/sk unknown
- 1998-07-15 IL IL13403898A patent/IL134038A0/xx unknown
- 1998-07-15 HU HU0002821A patent/HUP0002821A3/hu unknown
- 1998-07-15 EP EP98939678A patent/EP0998465B1/de not_active Expired - Lifetime
- 1998-07-15 CA CA002296739A patent/CA2296739C/fr not_active Expired - Fee Related
- 1998-07-15 MX MXPA00000252A patent/MXPA00000252A/es not_active IP Right Cessation
- 1998-07-15 BR BR9811013-6A patent/BR9811013A/pt not_active IP Right Cessation
- 1998-07-15 ES ES98939678T patent/ES2206978T3/es not_active Expired - Lifetime
- 1998-07-15 NZ NZ502276A patent/NZ502276A/en unknown
- 1998-07-15 RU RU2000103581/04A patent/RU2192420C2/ru not_active IP Right Cessation
- 1998-07-15 AU AU88104/98A patent/AU751090B2/en not_active Ceased
- 1998-07-15 DK DK98939678T patent/DK0998465T3/da active
- 1998-07-15 KR KR1020007000386A patent/KR20010021822A/ko not_active Ceased
- 1998-07-15 JP JP2000503067A patent/JP4443034B2/ja not_active Expired - Fee Related
- 1998-07-15 CZ CZ2000122A patent/CZ290908B6/cs not_active IP Right Cessation
- 1998-07-15 DE DE69818060T patent/DE69818060T2/de not_active Expired - Lifetime
- 1998-07-16 ZA ZA986334A patent/ZA986334B/xx unknown
2000
- 2000-01-06 NO NO20000055A patent/NO20000055L/no not_active Application Discontinuation
- 2000-01-14 US US09/480,965 patent/US6392042B1/en not_active Expired - Fee Related
2001
- 2001-11-21 US US09/990,015 patent/US20040209890A1/en not_active Abandoned

Also Published As

Publication number	Publication date
ES2206978T3 (es)	2004-05-16
US6392042B1 (en)	2002-05-21
DK0998465T3 (da)	2003-12-15
HUP0002821A3 (en)	2001-07-30
JP4443034B2 (ja)	2010-03-31
JP2001510186A (ja)	2001-07-31
AU8810498A (en)	1999-02-10
US20040209890A1 (en)	2004-10-21
RU2192420C2 (ru)	2002-11-10
CZ2000122A3 (cs)	2000-05-17
CN1264370A (zh)	2000-08-23
CZ290908B6 (cs)	2002-11-13
EP0998465B1 (de)	2003-09-10
PL338133A1 (en)	2000-09-25
WO1999003842A1 (fr)	1999-01-28
MXPA00000252A (es)	2002-04-24
IL134038A0 (en)	2001-04-30
HUP0002821A2 (hu)	2001-05-28
FR2766184A1 (fr)	1999-01-22
AU751090B2 (en)	2002-08-08
NO20000055D0 (no)	2000-01-06
CA2296739C (fr)	2008-09-23
ZA986334B (en)	1999-02-02
ATE249442T1 (de)	2003-09-15
EP0998465A1 (de)	2000-05-10
DE69818060D1 (de)	2003-10-16
NO20000055L (no)	2000-01-06
NZ502276A (en)	2001-09-28
FR2766184B1 (fr)	2000-11-17
KR20010021822A (ko)	2001-03-15
DE69818060T2 (de)	2004-07-08
BR9811013A (pt)	2000-08-15
CA2296739A1 (fr)	1999-01-28

Publication	Publication Date	Title
AU751090B2 (en)	2002-08-08	Polyhydroxyalkylpyrazine derivatives, preparation and medicines containing them
KR100648324B1 (ko)	2006-11-23	신규 폴리하이드록시피라진 유도체, 이의 제조방법 및이를 함유하는 약학 조성물
AU769948B2 (en)	2004-02-12	Polyhydroalkylpyrazine derivatives and their preparation and medicines containing them
SK452000A3 (en)	2000-06-12	Polyhydroxyalkylpyrazine derivatives, their preparation and medicines containing them
FR2766182A1 (fr)	1999-01-22	Medicaments contenant des derives de polyhydroxyalkylpyrazine, les nouveaux derives de polyhydroxyalkylpyrazine et leur preparation
CZ2001143A3 (cs)	2001-05-16	Léčiva obsahující deriváty polyhydroxyalkylpyrazinu, nové deriváty polyhydroxyalkylpyrazinu a způsob jejich přípravy