SK6092003A3 - Combination of GABA agonists and aldosereductase inhibitors - Google Patents

Combination of GABA agonists and aldosereductase inhibitors Download PDF

Info

Publication number: SK6092003A3
Authority: SK; Slovakia
Prior art keywords: pharmaceutically acceptable; prodrug; prodrugs; gamma; pharmaceutical composition
Prior art date: 2000-11-30

Application number

SK609-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Banavara Lakshman Mylari

Original Assignee

Pfizer Prod 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.)

2000-11-30

Filing date

2001-11-19

Publication date

2004-07-07

2001-11-19 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2004-07-07 Publication of SK6092003A3 publication Critical patent/SK6092003A3/sk

Links

239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 title claims abstract description 65
239000003288 aldose reductase inhibitor Substances 0.000 title claims description 46
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 title description 9
229940002612 prodrug Drugs 0.000 claims abstract description 91
239000000651 prodrug Substances 0.000 claims abstract description 91
150000003839 salts Chemical class 0.000 claims abstract description 62
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 41
241000124008 Mammalia Species 0.000 claims abstract description 12
208000002249 Diabetes Complications Diseases 0.000 claims abstract description 10
206010012655 Diabetic complications Diseases 0.000 claims abstract description 9
208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 7
208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 6
208000032781 Diabetic cardiomyopathy Diseases 0.000 claims abstract description 6
206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 6
208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 6
206010007749 Cataract diabetic Diseases 0.000 claims abstract description 5
206010063547 Diabetic macroangiopathy Diseases 0.000 claims abstract description 5
206010054044 Diabetic microangiopathy Diseases 0.000 claims abstract description 5
201000009101 diabetic angiopathy Diseases 0.000 claims abstract description 5
201000007025 diabetic cataract Diseases 0.000 claims abstract description 5
229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 37
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 35
150000001875 compounds Chemical class 0.000 claims description 32
AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 18
229960001233 pregabalin Drugs 0.000 claims description 17
229960002870 gabapentin Drugs 0.000 claims description 16
ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 claims description 16
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 13
PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 13
PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 claims description 13
KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 11
-1 progabid Chemical compound 0.000 claims description 11
229960000623 carbamazepine Drugs 0.000 claims description 10
FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 10
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 10
229960001848 lamotrigine Drugs 0.000 claims description 10
229960002036 phenytoin Drugs 0.000 claims description 10
229960001918 tiagabine Drugs 0.000 claims description 10
239000003085 diluting agent Substances 0.000 claims description 9
PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 claims description 9
KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 claims description 8
229960000794 baclofen Drugs 0.000 claims description 8
239000011230 binding agent Substances 0.000 claims description 8
229960004394 topiramate Drugs 0.000 claims description 8
229960005318 vigabatrin Drugs 0.000 claims description 8
NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 7
MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 claims description 7
229960000604 valproic acid Drugs 0.000 claims description 7
FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 claims description 6
229960004181 riluzole Drugs 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
208000025865 Ulcer Diseases 0.000 claims description 4
239000000556 agonist Substances 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
231100000397 ulcer Toxicity 0.000 claims description 4
BMHZAHGTGIZZCT-LJQANCHMSA-N (4r)-2-[(4-bromo-2-fluorophenyl)methyl]-6-fluorospiro[isoquinoline-4,3'-pyrrolidine]-1,2',3,5'-tetrone Chemical compound C1([C@]2(C(NC(=O)C2)=O)C2=O)=CC(F)=CC=C1C(=O)N2CC1=CC=C(Br)C=C1F BMHZAHGTGIZZCT-LJQANCHMSA-N 0.000 claims description 3
BUYWFAJWTSIACV-UHFFFAOYSA-N 2-[3-oxo-4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1,4-benzothiazin-2-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CN3C4=CC=CC=C4SC(C3=O)CC(=O)O)=NC2=C1F BUYWFAJWTSIACV-UHFFFAOYSA-N 0.000 claims description 3
BCSVCWVQNOXFGL-UHFFFAOYSA-N 3,4-dihydro-4-oxo-3-((5-trifluoromethyl-2-benzothiazolyl)methyl)-1-phthalazine acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 BCSVCWVQNOXFGL-UHFFFAOYSA-N 0.000 claims description 3
CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 claims description 3
229950010170 epalrestat Drugs 0.000 claims description 3
CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 claims description 3
229950007256 fidarestat Drugs 0.000 claims description 3
229950002259 minalrestat Drugs 0.000 claims description 3
229960002752 progabide Drugs 0.000 claims description 3
IBALRBWGSVJPAP-HEHNFIMWSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=N/CCCC(=O)N)/C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-HEHNFIMWSA-N 0.000 claims description 3
SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 claims description 3
229950006343 zenarestat Drugs 0.000 claims description 3
229950005346 zopolrestat Drugs 0.000 claims description 3
201000010099 disease Diseases 0.000 claims 1
WAAPEIZFCHNLKK-PELKAZGASA-N fidarestat Chemical compound C([C@@H](OC1=CC=C(F)C=C11)C(=O)N)[C@@]21NC(=O)NC2=O WAAPEIZFCHNLKK-PELKAZGASA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
238000000034 method Methods 0.000 abstract description 31
208000008960 Diabetic foot Diseases 0.000 abstract 1
239000000203 mixture Substances 0.000 description 37
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 30
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 15
229960003692 gamma aminobutyric acid Drugs 0.000 description 15
239000002775 capsule Substances 0.000 description 13
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
125000002091 cationic group Chemical group 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
102000005915 GABA Receptors Human genes 0.000 description 5
108010005551 GABA Receptors Proteins 0.000 description 5
241000282412 Homo Species 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
239000002585 base Substances 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
239000000463 material Substances 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
WAAPEIZFCHNLKK-UFBFGSQYSA-N (2s,4s)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide Chemical compound C([C@H](OC1=CC=C(F)C=C11)C(=O)N)[C@@]21NC(=O)NC2=O WAAPEIZFCHNLKK-UFBFGSQYSA-N 0.000 description 3
102000016912 Aldehyde Reductase Human genes 0.000 description 3
108010053754 Aldehyde reductase Proteins 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
150000001412 amines Chemical group 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
150000001732 carboxylic acid derivatives Chemical group 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
229940064790 dilantin Drugs 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000012458 free base Substances 0.000 description 3
229940084457 gabitril Drugs 0.000 description 3
239000008103 glucose Substances 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
229940072170 lamictal Drugs 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
229940072228 neurontin Drugs 0.000 description 3
239000002985 plastic film Substances 0.000 description 3
229920006255 plastic film Polymers 0.000 description 3
239000000243 solution Substances 0.000 description 3
239000012453 solvate Substances 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
229940035305 topamax Drugs 0.000 description 3
LKBFFDOJUKLQNY-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-4-oxo-1-phthalazinyl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=C(Br)C=C1F LKBFFDOJUKLQNY-UHFFFAOYSA-N 0.000 description 2
108010060511 4-Aminobutyrate Transaminase Proteins 0.000 description 2
102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
229910019142 PO4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000002249 anxiolytic agent Substances 0.000 description 2
230000000949 anxiolytic effect Effects 0.000 description 2
229940005530 anxiolytics Drugs 0.000 description 2
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 2
230000037396 body weight Effects 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
229960001231 choline Drugs 0.000 description 2
238000013270 controlled release Methods 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000011888 foil Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000006870 function Effects 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000005764 inhibitory process Effects 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
210000005036 nerve Anatomy 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
238000004806 packaging method and process Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
230000002195 synergetic effect Effects 0.000 description 2
238000003419 tautomerization reaction Methods 0.000 description 2
229940090016 tegretol Drugs 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
SRJRJOYFPZRDNH-NSHDSACASA-N (4s)-6-fluorospiro[3h-chromene-4,5'-imidazolidine]-2,4'-dione Chemical compound C12=CC(F)=CC=C2OC(=O)C[C@@]21NCNC2=O SRJRJOYFPZRDNH-NSHDSACASA-N 0.000 description 1
DYAOOYAQOGVEMJ-UHFFFAOYSA-N 2,7-difluoro-4-methoxyspiro[fluorene-9,4'-imidazolidine] Chemical compound COc1cc(F)cc2c1-c1ccc(F)cc1C21CNCN1 DYAOOYAQOGVEMJ-UHFFFAOYSA-N 0.000 description 1
XSHTXZXPLDNDKC-UHFFFAOYSA-N 2-[3-[(5,7-dichloro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC(Cl)=C2S1 XSHTXZXPLDNDKC-UHFFFAOYSA-N 0.000 description 1
FTPBFNMYCGQFGU-UHFFFAOYSA-N 2-[3-[(5,7-dichloro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC(Cl)=C2O1 FTPBFNMYCGQFGU-UHFFFAOYSA-N 0.000 description 1
KNWXUWPPDTZSFW-UHFFFAOYSA-N 2-[3-[(5,7-difluoro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC(F)=C2S1 KNWXUWPPDTZSFW-UHFFFAOYSA-N 0.000 description 1
GDULRSFIHLMHJW-UHFFFAOYSA-N 2-[3-[(5,7-difluoro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC(F)=C2O1 GDULRSFIHLMHJW-UHFFFAOYSA-N 0.000 description 1
LNCWRJYGGOAOMU-UHFFFAOYSA-N 2-[3-[(5-chloro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC=C2S1 LNCWRJYGGOAOMU-UHFFFAOYSA-N 0.000 description 1
LURVWPRCGVAWKT-UHFFFAOYSA-N 2-[3-[(5-chloro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC=C2O1 LURVWPRCGVAWKT-UHFFFAOYSA-N 0.000 description 1
QUBABKJOUGUHAK-UHFFFAOYSA-N 2-[3-[(5-fluoro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC=C2S1 QUBABKJOUGUHAK-UHFFFAOYSA-N 0.000 description 1
DGCTZGDPGOMMNB-UHFFFAOYSA-N 2-[3-oxo-2,8-di(propan-2-yl)-1,4-benzoxazin-4-yl]acetic acid Chemical compound C1=CC=C2N(CC(O)=O)C(=O)C(C(C)C)OC2=C1C(C)C DGCTZGDPGOMMNB-UHFFFAOYSA-N 0.000 description 1
QKRGDZKQCDTVMW-UHFFFAOYSA-N 2-[4-oxo-3-[[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]phthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2O1 QKRGDZKQCDTVMW-UHFFFAOYSA-N 0.000 description 1
JRGBXEJDIMXJAP-UHFFFAOYSA-N 2-fluorospiro[fluorene-9,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2C2=CC=CC=C2C21NC(=O)NC2=O JRGBXEJDIMXJAP-UHFFFAOYSA-N 0.000 description 1
NHLMYHQEHGRUJZ-UHFFFAOYSA-N 3-(5-fluoro-1,3-benzoxazol-2-yl)-2-(4-oxo-3h-phthalazin-1-yl)propanoic acid Chemical compound C1=CC=C2C(C(CC=3OC4=CC=C(F)C=C4N=3)C(=O)O)=NNC(=O)C2=C1 NHLMYHQEHGRUJZ-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
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
239000004135 Bone phosphate Substances 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
BUELMBFSPQNFIS-UHFFFAOYSA-N C=1(C=CC2=CCC=CC12)O Chemical compound C=1(C=CC2=CCC=CC12)O BUELMBFSPQNFIS-UHFFFAOYSA-N 0.000 description 1
DWTVLAFZRWBUGT-UHFFFAOYSA-N CC(O)=O.C1=CC=C2C=NCNC2=C1 Chemical compound CC(O)=O.C1=CC=C2C=NCNC2=C1 DWTVLAFZRWBUGT-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
208000002177 Cataract Diseases 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
108010062745 Chloride Channels Proteins 0.000 description 1
102000011045 Chloride Channels Human genes 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
208000012661 Dyskinesia Diseases 0.000 description 1
239000004097 EU approved flavor enhancer Substances 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
241001123946 Gaga Species 0.000 description 1
241000132519 Galactites Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
108090000862 Ion Channels Proteins 0.000 description 1
102000004310 Ion Channels Human genes 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
208000005392 Spasm Diseases 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
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
IDCBOTIENDVCBQ-UHFFFAOYSA-N TEPP Chemical compound CCOP(=O)(OCC)OP(=O)(OCC)OCC IDCBOTIENDVCBQ-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001323 aldoses Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
230000003281 allosteric effect Effects 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
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000000573 anti-seizure effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
230000008238 biochemical pathway Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 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
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
SLFUXNFVAANERW-UHFFFAOYSA-N ethyl hexanoate;potassium Chemical compound [K].CCCCCC(=O)OCC SLFUXNFVAANERW-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
235000019264 food flavour enhancer Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
150000004806 hydroxypyridines Chemical class 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000004973 liquid crystal related substance Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
230000003562 morphometric effect Effects 0.000 description 1
238000013425 morphometry Methods 0.000 description 1
239000002636 mycotoxin Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
GZCNKQPANHRSAJ-UHFFFAOYSA-N n-[3,5-dimethyl-4-(nitromethylsulfonyl)phenyl]-2-(2-methylphenyl)acetamide Chemical compound CC1=CC=CC=C1CC(=O)NC1=CC(C)=C(S(=O)(=O)C[N+]([O-])=O)C(C)=C1 GZCNKQPANHRSAJ-UHFFFAOYSA-N 0.000 description 1
230000007830 nerve conduction Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000003957 neurotransmitter release Effects 0.000 description 1
238000012858 packaging process Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
230000010287 polarization Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229950010884 ponalrestat Drugs 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000003518 presynaptic effect Effects 0.000 description 1
210000005215 presynaptic neuron Anatomy 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
FNXKBSAUKFCXIK-UHFFFAOYSA-M sodium;hydrogen carbonate;8-hydroxy-7-iodoquinoline-5-sulfonic acid Chemical class [Na+].OC([O-])=O.C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 FNXKBSAUKFCXIK-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
LXANPKRCLVQAOG-NSHDSACASA-N sorbinil Chemical compound C12=CC(F)=CC=C2OCC[C@@]21NC(=O)NC2=O LXANPKRCLVQAOG-NSHDSACASA-N 0.000 description 1
229950004311 sorbinil Drugs 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
ZVGYIXBHESYHCE-UHFFFAOYSA-N spiro[6H-quinoline-5,4'-imidazolidine] Chemical compound N1=CC=CC2=C1C=CCC21NCNC1 ZVGYIXBHESYHCE-UHFFFAOYSA-N 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
210000000225 synapse Anatomy 0.000 description 1
238000003786 synthesis reaction Methods 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
229960003069 tolrestat Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Landscapes

Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Cardiology (AREA)
Diabetes (AREA)
Biomedical Technology (AREA)
Ophthalmology & Optometry (AREA)
Hospice & Palliative Care (AREA)
Neurosurgery (AREA)
Heart & Thoracic Surgery (AREA)
Neurology (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Emergency Medicine (AREA)
Psychiatry (AREA)
Urology & Nephrology (AREA)
Physical Education & Sports Medicine (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK609-2003A 2000-11-30 2001-11-19 Combination of GABA agonists and aldosereductase inhibitors SK6092003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25044800P	2000-11-30	2000-11-30
PCT/IB2001/002214 WO2002043763A2 (en)	2000-11-30	2001-11-19	Combination of gaba agonists and aldose reductase inhibitors

Publications (1)

Publication Number	Publication Date
SK6092003A3 true SK6092003A3 (en)	2004-07-07

Family

ID=22947799

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK609-2003A SK6092003A3 (en)	2000-11-30	2001-11-19	Combination of GABA agonists and aldosereductase inhibitors

Country Status (34)

Country	Link
US (1)	US6720348B2 (cs)
EP (1)	EP1337272A2 (cs)
JP (1)	JP2004514700A (cs)
KR (1)	KR20030059287A (cs)
CN (1)	CN1477976A (cs)
AP (1)	AP2001002359A0 (cs)
AR (1)	AR031432A1 (cs)
AU (1)	AU2002215160A1 (cs)
BG (1)	BG107812A (cs)
BR (1)	BR0115776A (cs)
CA (1)	CA2430309A1 (cs)
CR (1)	CR6962A (cs)
CZ (1)	CZ20031387A3 (cs)
DO (1)	DOP2001000294A (cs)
EA (1)	EA200300433A1 (cs)
EC (1)	ECSP034629A (cs)
EE (1)	EE200300249A (cs)
HR (1)	HRP20030419A2 (cs)
HU (1)	HUP0302555A3 (cs)
IL (1)	IL155710A0 (cs)
IS (1)	IS6787A (cs)
MA (1)	MA26965A1 (cs)
MX (1)	MXPA03004871A (cs)
NO (1)	NO20032387L (cs)
OA (1)	OA12413A (cs)
PA (1)	PA8534201A1 (cs)
PE (1)	PE20020598A1 (cs)
PL (1)	PL365378A1 (cs)
SK (1)	SK6092003A3 (cs)
SV (1)	SV2003000752A (cs)
TN (1)	TNSN01170A1 (cs)
UY (1)	UY27044A1 (cs)
WO (1)	WO2002043763A2 (cs)
ZA (1)	ZA200303340B (cs)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL189872B1 (pl)	1996-07-24	2005-10-31	Warner Lambert Co	Zastosowanie izobutylogaby i jej pochodnych do wytwarzania leku do leczenia bólu
US6696407B1 (en) *	1997-03-21	2004-02-24	The Regents Of The University Of California	Huntington's disease treatment comprising administering aldose reductase inhibitors to increase striatal CNTF
US20030162754A1 (en) *	2001-12-17	2003-08-28	Tufts University	Use of GABA and GABAB agonists
WO2003105864A1 (en) *	2002-06-13	2003-12-24	Board Of Regents, The University Of Texas System	Methods and compositions involving aldose reductase inhibitors
AU2003303041B2 (en) *	2002-12-13	2008-07-24	Warner-Lambert Company Llc	Alpha-2-delta ligand to treat lower urinary tract symptoms
US20080318908A1 (en) *	2002-12-17	2008-12-25	Trustees Of Tufts College	Use of gaba and gabab agonists
AU2003301184A1 (en) *	2002-12-20	2004-07-22	Dynogen Pharmaceuticals Inc	METHODS OF TREATING NON-PAINFUL BLADDER DISORDERS USING Alpha2Delta SUBUNIT CALCIUM CHANNEL MODULATORS
AU2004224322A1 (en) *	2003-03-21	2004-10-07	Dynogen Pharmaceuticals, Inc.	Methods of treating lower urinary tract disorders using smooth muscle modulators and alpha-2-delta subunit calcium channel modulators
KR20050036195A (ko) *	2003-10-15	2005-04-20	고재영	신규한 망막병증 치료제 조성물
US20110092566A1 (en) *	2004-11-19	2011-04-21	Srivastava Satish K	Treatment of cancer with aldose reductase inhibitors
AU2006308889A1 (en) *	2005-10-31	2007-05-10	Braincells, Inc.	GABA receptor mediated modulation of neurogenesis
JP2009533368A (ja)	2006-04-11	2009-09-17	ノバルティスアクチエンゲゼルシャフト	有機化合物
US20130012485A1 (en) *	2006-12-22	2013-01-10	Baeschlin Daniel Kaspar	Organic compounds
EP2848252A3 (en)	2007-03-23	2015-06-17	The Board of Regents of the University of Texas System	Aldose reductase inhibitors for use in treating uveitis
US20090270490A1 (en) *	2008-04-24	2009-10-29	The Board Of Regents Of The University Of Texas System	Methods involving aldose reductase inhibition
SG157299A1 (en)	2008-05-09	2009-12-29	Agency Science Tech & Res	Diagnosis and treatment of kawasaki disease
US9623000B2 (en)	2008-07-31	2017-04-18	Dekel Pharmaceuticals Ltd	Compositions and methods for treating inflammatory disorders
PL2326632T3 (pl) *	2008-09-06	2017-10-31	Bionevia Pharmaceuticals Inc	Nowy kokryształ choliny i epalrestatu
WO2012088525A2 (en)	2010-12-23	2012-06-28	The Board Of Regents Of The University Of Texas System	Methods for treating copd
US8652527B1 (en)	2013-03-13	2014-02-18	Upsher-Smith Laboratories, Inc	Extended-release topiramate capsules
US9101545B2 (en)	2013-03-15	2015-08-11	Upsher-Smith Laboratories, Inc.	Extended-release topiramate capsules
US20180161388A1 (en) *	2015-05-18	2018-06-14	Beth Israel Deaconess Medical Center, Inc.	Substance p, mast cell degranulation inhibitors, and peripheral neuropathy
CN110769855A (zh) *	2017-04-21	2020-02-07	史蒂文·霍夫曼	用于治疗视网膜病变的组合物和方法
US12459965B2 (en)	2017-10-09	2025-11-04	Compass Pathfinder Limited	Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use
GB2571696B (en)	2017-10-09	2020-05-27	Compass Pathways Ltd	Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced
US12377112B2 (en)	2019-04-17	2025-08-05	Compass Pathfinder Limited	Methods of treating neurocognitive disorders, chronic pain and reducing inflammation
CN116235853B (zh) *	2022-12-28	2025-11-04	中国农业大学	一种植物生长调节剂及其在促进植物生长、提高植物产量和增强植物抗逆性中的应用

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH449645A (de)	1963-07-09	1968-01-15	Ciba Geigy	Verfahren zur Herstellung neuer Aminosäuren
CH427803A (de)	1963-12-06	1967-01-15	Geigy Ag J R	Verfahren zur Herstellung eines neuen Isoxazolderivates
DE2460891C2 (de) *	1974-12-21	1982-09-23	Gödecke AG, 1000 Berlin	1-Aminomethyl-1-cycloalkanessigsäuren und deren Ester, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
US3960927A (en)	1975-03-18	1976-06-01	Richardson-Merrell Inc.	Olefinic derivatives of amino acids
FR2319338A1 (fr)	1975-08-01	1977-02-25	Synthelabo	Nouveaux derives de a- phenyl benzylideniques des acides amines, leur preparation et les medicaments qui en contiennent
US4130714A (en)	1977-05-23	1978-12-19	Pfizer Inc.	Hydantoin therapeutic agents
IE47592B1 (en) *	1977-12-29	1984-05-02	Ici Ltd	Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture
DK153787C (da)	1979-06-01	1989-01-16	Wellcome Found	Analogifremgangsmaade til fremstilling af substituerede 3,5-diamino-6-phenyl-1,2,4-triaziner og alfa-cyanobenzyliden-aminoguanidinforbindelser til anvendelse som mellemprodukter herved
JPS5745185A (en)	1980-07-21	1982-03-13	Eisai Co Ltd	Hydantoin derivative and its preparation
JPS5740478A (en) *	1980-08-22	1982-03-06	Ono Pharmaceut Co Ltd	Rhodanine derivative, its preparation and aldose reductase inhibitor containing rhodanine derivative
US4791126A (en)	1980-08-22	1988-12-13	Ono Pharmaceutical Co., Ltd.	Rhodanine derivatives, process for their preparation, and aldose reductase inhibitor containing the rhodanine derivatives as active ingredients
FR2492258A1 (fr)	1980-10-17	1982-04-23	Pharmindustrie	Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole
CA1176269A (en)	1981-03-02	1984-10-16	Kazimir Sestanj	N-naphthoylglycine derivatives
US4436745A (en)	1982-04-15	1984-03-13	Alcon Laboratories, Inc.	Method of inhibiting aldose reductase activity
US4438272A (en)	1982-04-15	1984-03-20	Alcon Laboratories, Inc.	Spiro-(fluoren-9,4'-imidazolidine)-2',5'-diones
US4513006A (en)	1983-09-26	1985-04-23	Mcneil Lab., Inc.	Anticonvulsant sulfamate derivatives
US5066659A (en)	1984-10-30	1991-11-19	Pfizer Inc.	Spiro-heteroazalones for treatment of diabetic complications
DK288385D0 (da) *	1985-06-26	1985-06-26	Novo Industri As	Aminosyrederivater
GB8524663D0 (en)	1985-10-07	1985-11-13	Fujisawa Pharmaceutical Co	Quinazoline derivatives
US4939140A (en) *	1985-11-07	1990-07-03	Pfizer Inc.	Heterocyclic oxophthalazinyl acetic acids
AU602641B2 (en)	1986-04-17	1990-10-18	Senju Pharmaceutical Co., Ltd.	Thiolactam-N-acetic acid derivatives, their production and use
DE3769066D1 (de)	1986-08-28	1991-05-08	Sanwa Kagaku Kenkyusho Co	Hydantoin-derivate zur behandlung von komplikationen bei diabetes.
US4771052A (en) *	1987-02-05	1988-09-13	Hoechst-Roussel Pharmaceuticals, Inc.	Tetrahydropyrido[3',4':4,5]pyrrolo[2,3-c]quinolines and their use as hypotensive agents
GB8801037D0 (en)	1988-01-18	1988-02-17	Plessey Co Ltd	Improvements relating to fuel supply systems
US5252572A (en) *	1988-02-03	1993-10-12	Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt.	Pyridopyrimidine derivatives, pharmaceutical compositions containing them and process for preparing same
US4996204A (en) *	1989-05-11	1991-02-26	Pfizer Inc.	Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors
US4980357A (en)	1990-03-01	1990-12-25	Pfizer Inc.	Azolidinedione derivatives
US5037831A (en)	1990-05-21	1991-08-06	American Home Products Corporation	Spiro-isoquinoline-pyrrolidines and analogs thereof useful as aldose reductase inhibitors
US5236945A (en) *	1990-06-11	1993-08-17	Pfizer Inc.	1H-indazole-3-acetic acids as aldose reductase inhibitors
GB9016978D0 (en)	1990-08-02	1990-09-19	Ici Plc	Acetamide derivatives
US6197819B1 (en) *	1990-11-27	2001-03-06	Northwestern University	Gamma amino butyric acid analogs and optical isomers
US5728704A (en) *	1992-09-28	1998-03-17	Pfizer Inc.	Substituted pyridmidines for control of diabetic complications
FR2774908B1 (fr) *	1998-02-17	2000-06-23	Centre Nat Rech Scient	Utilisation d'inhibiteur de la liberation du glutamate dans le traitement de l'ischemie retinienne
GB0001662D0 (en) *	1999-02-06	2000-03-15	Zeneca Ltd	Pharmaceutical compositions
US6350769B1 (en) *	1999-02-24	2002-02-26	The Regents Of The University Of California	Gaba alpha receptors mediate inhibition of T cell responses
PT1041068E (pt) *	1999-04-01	2004-07-30	Pfizer Prod Inc	Compostos para o tratamento e prevencao de complicacoes diabeticas
WO2000061138A1 (en) *	1999-04-08	2000-10-19	Ortho-Mcneil Pharmaceutical, Inc.	Anticonvulsant derivatives useful in treating chronic neurodegenerative disorders

2001
- 2001-11-19 WO PCT/IB2001/002214 patent/WO2002043763A2/en not_active Ceased
- 2001-11-19 JP JP2002545733A patent/JP2004514700A/ja not_active Withdrawn
- 2001-11-19 EE EEP200300249A patent/EE200300249A/xx unknown
- 2001-11-19 HR HR20030419A patent/HRP20030419A2/hr not_active Application Discontinuation
- 2001-11-19 KR KR10-2003-7007221A patent/KR20030059287A/ko not_active Ceased
- 2001-11-19 HU HU0302555A patent/HUP0302555A3/hu unknown
- 2001-11-19 MX MXPA03004871A patent/MXPA03004871A/es unknown
- 2001-11-19 AP APAP/P/2001/002359A patent/AP2001002359A0/en unknown
- 2001-11-19 OA OA1200300138A patent/OA12413A/en unknown
- 2001-11-19 EP EP01983740A patent/EP1337272A2/en not_active Withdrawn
- 2001-11-19 PL PL01365378A patent/PL365378A1/xx not_active Application Discontinuation
- 2001-11-19 IL IL15571001A patent/IL155710A0/xx unknown
- 2001-11-19 AU AU2002215160A patent/AU2002215160A1/en not_active Abandoned
- 2001-11-19 BR BR0115776-0A patent/BR0115776A/pt not_active IP Right Cessation
- 2001-11-19 CZ CZ20031387A patent/CZ20031387A3/cs unknown
- 2001-11-19 EA EA200300433A patent/EA200300433A1/ru unknown
- 2001-11-19 SK SK609-2003A patent/SK6092003A3/sk not_active Application Discontinuation
- 2001-11-19 CN CNA018195954A patent/CN1477976A/zh active Pending
- 2001-11-19 CA CA002430309A patent/CA2430309A1/en not_active Abandoned
- 2001-11-26 DO DO2001000294A patent/DOP2001000294A/es unknown
- 2001-11-27 PE PE2001001187A patent/PE20020598A1/es not_active Application Discontinuation
- 2001-11-28 AR ARP010105542A patent/AR031432A1/es not_active Application Discontinuation
- 2001-11-28 UY UY27044A patent/UY27044A1/es not_active Application Discontinuation
- 2001-11-29 TN TNTNSN01170A patent/TNSN01170A1/fr unknown
- 2001-11-29 US US09/997,039 patent/US6720348B2/en not_active Expired - Fee Related
- 2001-11-30 PA PA20018534201A patent/PA8534201A1/es unknown
- 2001-11-30 SV SV2001000752A patent/SV2003000752A/es unknown
2003
- 2003-04-14 IS IS6787A patent/IS6787A/is unknown
- 2003-04-24 CR CR6962A patent/CR6962A/es not_active Application Discontinuation
- 2003-04-30 ZA ZA200303340A patent/ZA200303340B/en unknown
- 2003-05-13 BG BG107812A patent/BG107812A/bg unknown
- 2003-05-20 MA MA27166A patent/MA26965A1/fr unknown
- 2003-05-27 NO NO20032387A patent/NO20032387L/no not_active Application Discontinuation
- 2003-05-28 EC EC2003004629A patent/ECSP034629A/es unknown

Also Published As

Publication number	Publication date
CN1477976A (zh)	2004-02-25
BG107812A (bg)	2004-02-27
AR031432A1 (es)	2003-09-24
TNSN01170A1 (fr)	2005-11-10
EA200300433A1 (ru)	2003-10-30
HUP0302555A2 (hu)	2003-11-28
PL365378A1 (en)	2005-01-10
WO2002043763A2 (en)	2002-06-06
US6720348B2 (en)	2004-04-13
ECSP034629A (es)	2003-07-25
HRP20030419A2 (en)	2004-08-31
KR20030059287A (ko)	2003-07-07
PE20020598A1 (es)	2002-07-08
JP2004514700A (ja)	2004-05-20
SV2003000752A (es)	2003-01-13
CZ20031387A3 (cs)	2004-04-14
EE200300249A (et)	2003-10-15
BR0115776A (pt)	2004-01-13
CR6962A (es)	2004-02-02
MA26965A1 (fr)	2004-12-20
NO20032387D0 (no)	2003-05-27
UY27044A1 (es)	2002-07-31
AU2002215160A1 (en)	2002-06-11
IS6787A (is)	2003-04-14
IL155710A0 (en)	2003-11-23
DOP2001000294A (es)	2002-08-30
AP2001002359A0 (en)	2001-12-31
MXPA03004871A (es)	2003-08-19
EP1337272A2 (en)	2003-08-27
NO20032387L (no)	2003-05-27
ZA200303340B (en)	2004-04-30
HUP0302555A3 (en)	2005-06-28
CA2430309A1 (en)	2002-06-06
WO2002043763A3 (en)	2003-03-13
OA12413A (en)	2004-09-30
PA8534201A1 (es)	2002-10-24
US20020077319A1 (en)	2002-06-20

Legal Events

Date	Code	Title	Description
2011-03-04	FC9A	Refused patent application

Publication	Publication Date	Title
SK6092003A3 (en)	2004-07-07	Combination of GABA agonists and aldosereductase inhibitors
JP5980840B2 (ja)	2016-08-31	インスリン感受性を増すための組成物および方法
US6413965B1 (en)	2002-07-02	Compositions and treatment for diabetic complications
EP1337271B1 (en)	2004-11-03	Combination of gaba agonists and sorbitol dehydrogenase inhibitors
AU2004271740B2 (en)	2010-10-28	Benzothiazole derivatives for the treatment of diabetes
JP2001163805A (ja)	2001-06-19	糖尿病性合併症治療用のアルドース還元酵素阻害剤と抗高血圧剤の組合せ
JP2007517901A (ja)	2007-07-05	体重の減少に作用する鎮痙剤及び抗精神病剤の組成物
CA2514574A1 (en)	2004-08-12	Use of sodium channel modulators for treating gastrointestinal tract disorders
JPH07504915A (ja)	1995-06-01	ムスカリン拮抗物質投与による，哺乳動物の眼における眼内圧低下法
US6380200B1 (en)	2002-04-30	Combination of aldose reductase inhibitors and selective serotonin reuptake inhibitors for the treatment of diabetic complications
US6436944B1 (en)	2002-08-20	Combination effective for the treatment of impotence
US6426341B1 (en)	2002-07-30	Treatment for diabetic complications
HK1059382A (en)	2004-07-02	Combination of gaba agonists and aldose reductase inhibitors